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    Clinical Trial Results:
    A Randomised, Double-blind, Placebo-controlled, Response-adaptive Dose-finding Trial Investigating the Efficacy, Safety and Tolerability of Oral Doses of FE 201836, with Desmopressin Orally Disintegrating Tablet as a Benchmark, During 12 Weeks of Treatment for Nocturia due to Nocturnal Polyuria in Adults

    Summary
    EudraCT number
    		 2016-003851-31
    Trial protocol
    		 CZ   HU   BE  
    Global end of trial date
    31 Oct 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Nov 2020
    First version publication date
    13 Nov 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    000233
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03201419
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ferring Pharmaceuticals A/S
    Sponsor organisation address
    International PharmaScience Center, Kay Fiskers Plads 11, Copenhagen S, Denmark, 2300
    Public contact
    Global Clinical Compliance, Ferring pharmaceuticals, DK0-Disclosure@ferring.com
    Scientific contact
    Global Clinical Compliance, Ferring pharmaceuticals, DK0-Disclosure@ferring.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Dec 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Oct 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Oct 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To establish the dose-response of FE 201836 with respect to the number of nocturnal voids in subjects with nocturia due to nocturnal polyuria.
    Protection of trial subjects
    The trial was performed in accordance with the Declaration of Helsinki and its amendments in force at the initiation of the trial, the consolidated International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use-Good Clinical Practice (ICH-GCP), the European Union (EU) Clinical Trials Directive, and applicable national laws in the countries where the trial was conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Jul 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 64
    Country: Number of subjects enrolled
    United States: 420
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Czech Republic: 32
    Country: Number of subjects enrolled
    Hungary: 11
    Worldwide total number of subjects
    531
    EEA total number of subjects
    47
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    330
    From 65 to 84 years
    198
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 71 sites were authorised to recruit subjects for the trial between July 2017 and July 2019. The trial sites that screened subjects to the trial were: 5 in Belgium, 10 in Canada, 5 in Czech Republic, 2 in Germany, 5 in Hungary, 1 in Poland and 43 in the United States of America (USA).

    Pre-assignment
    Screening details
    		 A total of 1721 subjects were screened, wherein, 531 met the eligibility criteria and entered the enrichment period. Of these, 302 subjects met the eligibility criteria at Visit (V) 4 (randomisation), and were randomised to treatment with FE 201836 (different doses), placebo, or desmopressin. A total of 278 subjects completed the trial.

    Period 1
    Period 1 title
    Randomised Treatment Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 FE 201836 500 µg (Randomised Treatment Period)
    Arm description
    		 FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT)
    Arm type
    		 Experimental

    Investigational medicinal product name
    FE 201836 500 µg
    Investigational medicinal product code
    FE 201836
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    FE 201836 500 µg oral solution and placebo ODT, administered once daily

    Arm title
    		 FE 201836 350 µg (Randomised Treatment Period)
    Arm description
    		 FE 201836 350 µg oral solution and placebo ODT
    Arm type
    		 Experimental

    Investigational medicinal product name
    FE 201836 350 µg
    Investigational medicinal product code
    FE 201836
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    FE 201836 350 µg oral solution and placebo ODT, administered once daily

    Arm title
    		 FE 201836 250 µg (Randomised Treatment Period)
    Arm description
    		 FE 201836 250 µg oral solution and placebo ODT
    Arm type
    		 Experimental

    Investigational medicinal product name
    FE 201836 250 µg
    Investigational medicinal product code
    FE 201836
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    FE 201836 250 µg oral solution and placebo ODT, administered once daily

    Arm title
    		 FE 201836 150 µg (Randomised Treatment Period)
    Arm description
    		 FE 201836 150 µg oral solution and placebo ODT
    Arm type
    		 Experimental

    Investigational medicinal product name
    FE 201836 150 µg
    Investigational medicinal product code
    FE 201836
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    FE 201836 150 µg oral solution and placebo ODT, administered once daily

    Arm title
    		 FE 201836 100 µg (Randomised Treatment Period)
    Arm description
    		 FE 201836 100 µg oral solution and placebo ODT
    Arm type
    		 Experimental

    Investigational medicinal product name
    FE 201836 100 µg
    Investigational medicinal product code
    FE 201836
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    FE 201836 100 µg oral solution and placebo ODT, administered once daily

    Arm title
    		 FE 201836 50 µg (Randomised Treatment Period)
    Arm description
    		 FE 201836 50 µg oral solution and placebo ODT
    Arm type
    		 Experimental

    Investigational medicinal product name
    FE 201836 50 µg
    Investigational medicinal product code
    FE 201836
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    FE 201836 50 µg oral solution and placebo ODT, administered once daily

    Arm title
    		 Placebo (Randomised Treatment Period)
    Arm description
    		 Placebo oral solution and placebo ODT
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution, Orodispersible tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo oral solution and placebo ODT, administered once daily

    Arm title
    		 Desmopressin 25 µg (Randomised Treatment Period)
    Arm description
    		 Desmopressin 25 µg ODT and placebo oral solution
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Desmopressin 25 µg (Randomised Treatment Period)
    Investigational medicinal product code
    Other name
    NOCDURNA
    Pharmaceutical forms
    Orodispersible tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Desmopressin 25 µg ODT and placebo oral solution, administered once daily (female subjects)

    Arm title
    		 Desmopressin 50 µg (Randomised Treatment Period)
    Arm description
    		 Desmopressin 50 µg ODT and placebo oral solution
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Desmopressin 50 μg (Randomised Treatment Period)
    Investigational medicinal product code
    Other name
    NOCDURNA
    Pharmaceutical forms
    Orodispersible tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Desmopressin 50 μg ODT and placebo oral solution, administered once daily (male subjects)

    Number of subjects in period 1 [1]
    		FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period) Desmopressin 25 µg (Randomised Treatment Period) Desmopressin 50 µg (Randomised Treatment Period)
    Started
    60
    27
    24
    14
    13
    34
    87
    26
    17
    Completed
    52
    24
    22
    14
    12
    33
    81
    25
    15
    Not completed
    8
    3
    2
    0
    1
    1
    6
    1
    2
         Consent withdrawn by subject
    4
    2
    1
    -
    -
    -
    -
    1
    2
         Adverse event, non-fatal
    3
    1
    -
    -
    1
    1
    5
    -
    -
         Other
    -
    -
    1
    -
    -
    -
    -
    -
    -
         Lost to follow-up
    1
    -
    -
    -
    -
    -
    -
    -
    -
         Protocol deviation
    -
    -
    -
    -
    -
    -
    1
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A total of 531 subjects met eligibility criteria and entered enrichment period (including active run-in period and washout period). During active run-in period subjects received FE 201836 500 µg and placebo to assess safety and establish subjects who respond to treatment with FE 201836 for inclusion in the trial (enrichment design). Of these, 302 subjects met eligibility criteria at V4 (randomisation), and were randomised to treatment with FE 201836 (different doses), placebo and desmopressin.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    FE 201836 500 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT)

    Reporting group title
    FE 201836 350 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 350 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 250 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 250 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 150 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 150 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 100 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 100 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 50 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 50 µg oral solution and placebo ODT

    Reporting group title
    Placebo (Randomised Treatment Period)
    Reporting group description
    		 Placebo oral solution and placebo ODT

    Reporting group title
    Desmopressin 25 µg (Randomised Treatment Period)
    Reporting group description
    		 Desmopressin 25 µg ODT and placebo oral solution

    Reporting group title
    Desmopressin 50 µg (Randomised Treatment Period)
    Reporting group description
    		 Desmopressin 50 µg ODT and placebo oral solution

    Reporting group values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period) Desmopressin 25 µg (Randomised Treatment Period) Desmopressin 50 µg (Randomised Treatment Period) Total
    Number of subjects
    		 60 27 24 14 13 34 87 26 17 302
    Age categorical
    Units: Subjects
        <65 years old
    		 35 19 14 6 6 21 52 24 11 188
        >=65 years old
    		 25 8 10 8 7 13 35 2 6 114
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 59.0 ( 14.1 ) 58.0 ( 14.3 ) 60.8 ( 13.0 ) 63.9 ( 7.5 ) 61.5 ( 9.2 ) 59.1 ( 10.4 ) 58.9 ( 13.9 ) 51.1 ( 11.1 ) 60.9 ( 9.5 ) -
    Gender categorical
    Units: Subjects
        Female
    		 40 18 16 5 8 16 51 26 0 180
        Male
    		 20 9 8 9 5 18 36 0 17 122
    Baseline body mass index (BMI)
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 30.66 ( 6.05 ) 29.91 ( 4.64 ) 29.56 ( 6.50 ) 32.03 ( 8.26 ) 31.52 ( 4.60 ) 30.93 ( 6.16 ) 29.54 ( 5.14 ) 31.89 ( 7.99 ) 31.05 ( 6.49 ) -
    Mean Number of Nocturnal Voids
    FE 201836 500 ug: n=59; Placebo: n=86; Desmopressin 25μg: n=25 Total: n=299
    Units: nocturnal voids
        arithmetic mean (standard deviation)
    		 2.88 ( 0.84 ) 3.01 ( 0.72 ) 3.10 ( 1.11 ) 2.98 ( 0.84 ) 3.33 ( 0.82 ) 3.24 ( 1.18 ) 3.09 ( 0.83 ) 3.38 ( 1.45 ) 3.16 ( 1.22 ) -
    Mean Nocturnal Urine Volume (NUV)
    FE 201836 500 ug: n=58; FE 201836 350 ug: n=26; Placebo: n=86; Desmopressin 25μg: n=25 Total: n=297
    Units: mL
        arithmetic mean (standard deviation)
    		 804.6 ( 313.8 ) 766.0 ( 242.1 ) 897.3 ( 373.6 ) 803.1 ( 304.7 ) 892.4 ( 206.7 ) 879.9 ( 354.1 ) 752.3 ( 269.5 ) 839.3 ( 286.4 ) 803.5 ( 425.8 ) -
    Mean Nocturnal Polyuria Index
    FE 201836 500 ug: n=55; FE 201836 350 ug: n=25; FE 201836 250 ug: n=22; FE 201836 100 ug: n=12; FE 201836 50 ug: n=31; Placebo: n=76; Desmopressin 25μg: n=23; Desmopressin 50 μg: n=16 Total: n=274
    Units: percentage
        arithmetic mean (standard deviation)
    		 48.87 ( 12.04 ) 46.76 ( 10.08 ) 49.75 ( 15.96 ) 50.99 ( 12.93 ) 44.59 ( 6.58 ) 47.01 ( 9.86 ) 47.91 ( 14.29 ) 49.21 ( 13.93 ) 49.10 ( 17.93 ) -
    Mean Nocturia Impact (NI) Diary Total Score
    FE 201836 350 ug: n=26; FE 201836 50 ug: n=32; Placebo: n=86; Desmopressin 25μg: n=25 Total: n=297
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 47.20 ( 18.39 ) 47.03 ( 28.44 ) 38.76 ( 19.09 ) 36.28 ( 22.10 ) 51.63 ( 17.73 ) 42.46 ( 23.28 ) 47.66 ( 21.25 ) 58.06 ( 20.78 ) 39.88 ( 23.08 ) -
    Mean NI Diary Overall Impact Score
    FE 201836 350 ug: n=26; FE 201836 50 ug: n=32; Placebo: n=86; Desmopressin 25μg: n=25 Total: n=297
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 59.2 ( 25.4 ) 62.3 ( 29.8 ) 55.9 ( 21.6 ) 53.0 ( 30.6 ) 68.6 ( 20.7 ) 59.9 ( 26.8 ) 62.7 ( 26.8 ) 71.5 ( 23.8 ) 54.2 ( 28.0 ) -
    Insomnia Severity Index (ISI)
    FE201836 500 ug: n=55; FE 201836 350 ug: n=26; FE 201836 100 ug: n=9; FE 201836 50 ug: n=31; Placebo: n=77 Total: n=279
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 15.8 ( 5.4 ) 15.7 ( 6.1 ) 14.3 ( 5.1 ) 13.0 ( 6.7 ) 16.4 ( 5.6 ) 14.7 ( 4.8 ) 15.6 ( 5.8 ) 18.2 ( 4.7 ) 15.5 ( 6.8 ) -
    Subject analysis sets

    Subject analysis set title
    ITT-RT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT-RT comprised of all the subjects randomised at V4.

    Subject analysis sets values
    		 ITT-RT
    Number of subjects
    302
    Age categorical
    Units: Subjects
        <65 years old
    188
        >=65 years old
    114
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    58.8 ( 12.8 )
    Gender categorical
    Units: Subjects
        Female
    180
        Male
    122
    Baseline body mass index (BMI)
    Units: kg/m^2
        arithmetic mean (standard deviation)
    30.44 ( 6.00 )
    Mean Number of Nocturnal Voids
    FE 201836 500 ug: n=59; Placebo: n=86; Desmopressin 25μg: n=25 Total: n=299
    Units: nocturnal voids
        arithmetic mean (standard deviation)
    3.09 ( 0.98 )
    Mean Nocturnal Urine Volume (NUV)
    FE 201836 500 ug: n=58; FE 201836 350 ug: n=26; Placebo: n=86; Desmopressin 25μg: n=25 Total: n=297
    Units: mL
        arithmetic mean (standard deviation)
    808.8 ( 307.5 )
    Mean Nocturnal Polyuria Index
    FE 201836 500 ug: n=55; FE 201836 350 ug: n=25; FE 201836 250 ug: n=22; FE 201836 100 ug: n=12; FE 201836 50 ug: n=31; Placebo: n=76; Desmopressin 25μg: n=23; Desmopressin 50 μg: n=16 Total: n=274
    Units: percentage
        arithmetic mean (standard deviation)
    48.24 ( 12.99 )
    Mean Nocturia Impact (NI) Diary Total Score
    FE 201836 350 ug: n=26; FE 201836 50 ug: n=32; Placebo: n=86; Desmopressin 25μg: n=25 Total: n=297
    Units: score on a scale
        arithmetic mean (standard deviation)
    46.30 ( 21.81 )
    Mean NI Diary Overall Impact Score
    FE 201836 350 ug: n=26; FE 201836 50 ug: n=32; Placebo: n=86; Desmopressin 25μg: n=25 Total: n=297
    Units: score on a scale
        arithmetic mean (standard deviation)
    61.2 ( 26.3 )
    Insomnia Severity Index (ISI)
    FE201836 500 ug: n=55; FE 201836 350 ug: n=26; FE 201836 100 ug: n=9; FE 201836 50 ug: n=31; Placebo: n=77 Total: n=279
    Units: score on a scale
        arithmetic mean (standard deviation)
    15.6 ( 5.6 )

    End points

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    End points reporting groups
    Reporting group title
    FE 201836 500 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 500 μg oral solution and placebo orally disintegrating tablet (ODT)

    Reporting group title
    FE 201836 350 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 350 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 250 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 250 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 150 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 150 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 100 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 100 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 50 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 50 µg oral solution and placebo ODT

    Reporting group title
    Placebo (Randomised Treatment Period)
    Reporting group description
    		 Placebo oral solution and placebo ODT

    Reporting group title
    Desmopressin 25 µg (Randomised Treatment Period)
    Reporting group description
    		 Desmopressin 25 µg ODT and placebo oral solution

    Reporting group title
    Desmopressin 50 µg (Randomised Treatment Period)
    Reporting group description
    		 Desmopressin 50 µg ODT and placebo oral solution

    Subject analysis set title
    ITT-RT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT-RT comprised of all the subjects randomised at V4.

    Primary: Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment

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    End point title
    		 Change From Baseline in Aggregated Mean Number of Nocturnal Voids During 12 Weeks of Treatment [1]
    End point description
    Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits. Level estimated for baseline value of mean number of nocturnal voids equal to 2 and 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval are presented in this endpoint. The analysis population included intention-to-treat analysis set for the randomised treatment period (ITT-RT) which comprised of all the subjects randomised at Visit 4.
    End point type
    Primary
    End point timeframe
    Baseline, during 12 weeks of treatment
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. The primary analyses did not include data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    60
    27
    24
    14
    13
    34
    87
    Units: nocturnal voids
        arithmetic mean (confidence interval 95%)
    -1.06 (-1.28 to -0.86)
    -0.99 (-1.20 to -0.78)
    -0.89 (-1.12 to -0.69)
    -0.80 (-1.00 to -0.62)
    -0.77 (-0.97 to -0.59)
    -0.76 (-0.95 to -0.58)
    -0.76 (-0.95 to -0.58)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.54
         upper limit
    		 -0.07
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.46
         upper limit
    		 -0.02
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.36
         upper limit
    		 0
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.23
         upper limit
    		 0
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.07
         upper limit
    		 0

    Secondary: Change From Baseline in Mean Number of Nocturnal Voids at Week 1

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    End point title
    		 Change From Baseline in Mean Number of Nocturnal Voids at Week 1 [2]
    End point description
    Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2. MMRM=Mixed Model for Repeated Measurements. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    54
    24
    24
    14
    11
    33
    80
    Units: nocturnal voids
        arithmetic mean (confidence interval 95%)
    -0.714 (-1.005 to -0.424)
    -1.162 (-1.577 to -0.747)
    -0.722 (-1.149 to -0.296)
    -0.520 (-1.058 to 0.017)
    -0.722 (-1.318 to -0.126)
    -0.325 (-0.709 to 0.059)
    -0.575 (-0.842 to -0.308)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4214 [3]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -0.139
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.48
         upper limit
    		 0.201
    Notes
    [3] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0101 [4]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -0.587
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.034
         upper limit
    		 -0.141
    Notes
    [4] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5203 [5]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.148
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.599
         upper limit
    		 0.304
    Notes
    [5] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8483 [6]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.055
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.508
         upper limit
    		 0.617
    Notes
    [6] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6357 [7]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.147
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.759
         upper limit
    		 0.464
    Notes
    [7] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2222 [8]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.152
         upper limit
    		 0.652
    Notes
    [8] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean Number of Nocturnal Voids at Week 4

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    End point title
    		 Change From Baseline in Mean Number of Nocturnal Voids at Week 4 [9]
    End point description
    Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    50
    22
    21
    12
    12
    31
    76
    Units: nocturnal voids
        arithmetic mean (confidence interval 95%)
    -1.078 (-1.345 to -0.811)
    -1.330 (-1.708 to -0.952)
    -0.784 (-1.181 to -0.386)
    -0.471 (-0.969 to 0.028)
    -0.952 (-1.469 to -0.435)
    -0.518 (-0.866 to -0.171)
    -0.912 (-1.152 to -0.673)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    126
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2909 [10]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.166
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.474
         upper limit
    		 0.143
    Notes
    [10] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.044 [11]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.418
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.824
         upper limit
    		 -0.011
    Notes
    [11] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5438 [12]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.128
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.288
         upper limit
    		 0.545
    Notes
    [12] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.096 [13]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.441
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.079
         upper limit
    		 0.962
    Notes
    [13] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8826 [14]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.568
         upper limit
    		 0.488
    Notes
    [14] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0344 [15]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.394
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.029
         upper limit
    		 0.759
    Notes
    [15] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean Number of Nocturnal Voids at Week 8

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    End point title
    		 Change From Baseline in Mean Number of Nocturnal Voids at Week 8 [16]
    End point description
    Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    44
    23
    21
    14
    12
    30
    70
    Units: nocturnal voids
        arithmetic mean (confidence interval 95%)
    -1.085 (-1.394 to -0.776)
    -1.177 (-1.603 to -0.751)
    -0.965 (-1.414 to -0.516)
    -0.490 (-1.037 to 0.058)
    -1.077 (-1.671 to -0.484)
    -0.786 (-1.187 to -0.386)
    -0.953 (-1.233 to -0.672)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4732 [17]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.132
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.496
         upper limit
    		 0.231
    Notes
    [17] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3394 [18]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.224
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.685
         upper limit
    		 0.237
    Notes
    [18] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.96 [19]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.488
         upper limit
    		 0.463
    Notes
    [19] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1131 [20]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.463
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.111
         upper limit
    		 1.037
    Notes
    [20] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6853 [21]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.124
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.729
         upper limit
    		 0.48
    Notes
    [21] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4364 [22]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.166
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.254
         upper limit
    		 0.587
    Notes
    [22] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean Number of Nocturnal Voids at Week 12

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    End point title
    		 Change From Baseline in Mean Number of Nocturnal Voids at Week 12 [23]
    End point description
    Nocturnal voids were defined as voids occuring from 5 minutes after bedtime until rising in the morning. The number of nocturnal voids at each visit was calculated as the average over the 3 consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in nocturnal voids are estimated using a baseline value of 2. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    40
    19
    19
    14
    11
    29
    69
    Units: nocturnal voids
        arithmetic mean (confidence interval 95%)
    -1.256 (-1.568 to -0.944)
    -1.120 (-1.558 to -0.683)
    -0.850 (-1.301 to -0.400)
    -0.674 (-1.206 to -0.142)
    -1.053 (-1.650 to -0.456)
    -0.921 (-1.317 to -0.524)
    -0.957 (-1.237 to -0.677)
    Statistical analysis title
    		 FE 201836 500 μg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1106 [24]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -0.299
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.667
         upper limit
    		 0.069
    Notes
    [24] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 μg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5005 [25]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -0.163
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.639
         upper limit
    		 0.313
    Notes
    [25] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 μg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6604 [26]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    0.107
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.372
         upper limit
    		 0.586
    Notes
    [26] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 μg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3178 [27]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    0.283
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.275
         upper limit
    		 0.842
    Notes
    [27] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 μg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7561 [28]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -0.096
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.701
         upper limit
    		 0.51
    Notes
    [28] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 μg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8614 [29]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    0.037
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.378
         upper limit
    		 0.452
    Notes
    [29] - Threshold for significance at 0.05 level.

    Secondary: Responder Rate in Nocturnal Voids at Week 1

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    End point title
    		 Responder Rate in Nocturnal Voids at Week 1 [30]
    End point description
    Defined as 50% reduction in nocturnal voids from baseline. Adjusted visit-specific estimated odds of at least 50% reduction mean number of nocturnal voids are estimated using a baseline value of 2. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Week 1
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    54
    24
    24
    14
    11
    33
    80
    Units: odds for nocturnal voids
        arithmetic mean (confidence interval 95%)
    0.844 (0.457 to 1.558)
    1.202 (0.510 to 2.833)
    0.682 (0.280 to 1.662)
    0.818 (0.269 to 2.490)
    0.810 (0.240 to 2.738)
    0.513 (0.227 to 1.157)
    0.480 (0.272 to 0.848)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.117 [31]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.759
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.869
         upper limit
    		 3.56
    Notes
    [31] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.048 [32]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.505
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.01
         upper limit
    		 6.214
    Notes
    [32] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.46 [33]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 3.602
    Notes
    [33] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.367 [34]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.704
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.535
         upper limit
    		 5.427
    Notes
    [34] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.407 [35]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.689
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.489
         upper limit
    		 5.825
    Notes
    [35] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.876 [36]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.069
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.462
         upper limit
    		 2.473
    Notes
    [36] - Threshold for significance at 0.05 level.

    Secondary: Responder Rate in Nocturnal Voids at Week 4

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    End point title
    		 Responder Rate in Nocturnal Voids at Week 4 [37]
    End point description
    Defined as 50% reduction in nocturnal voids from baseline. Adjusted visit-specific estimated odds of at least 50% reduction mean number of nocturnal voids are estimated using a baseline value of 2. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Week 4
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    50
    22
    21
    12
    12
    31
    76
    Units: odds of nocturnal voids
        arithmetic mean (confidence interval 95%)
    1.199 (0.633 to 2.270)
    5.851 (1.511 to 22.650)
    0.634 (0.255 to 1.575)
    0.534 (0.165 to 1.731)
    1.760 (0.470 to 6.596)
    0.683 (0.301 to 1.550)
    1.235 (0.686 to 2.224)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    126
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.937 [38]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.971
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 2.005
    Notes
    [38] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.028 [39]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.738
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.183
         upper limit
    		 18.968
    Notes
    [39] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.166 [40]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.513
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 1.318
    Notes
    [40] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.174 [41]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.433
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.129
         upper limit
    		 1.447
    Notes
    [41] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.608 [42]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.425
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.369
         upper limit
    		 5.512
    Notes
    [42] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.171 [43]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.553
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.237
         upper limit
    		 1.292
    Notes
    [43] - Threshold for significance at 0.05 level.

    Secondary: Responder Rate in Nocturnal Voids at Week 8

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    End point title
    		 Responder Rate in Nocturnal Voids at Week 8 [44]
    End point description
    Defined as 50% reduction in nocturnal voids from baseline. Adjusted visit-specific estimated odds of at least 50% reduction mean number of nocturnal voids are estimated using a baseline value of 2. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Week 8
    Notes
    [44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    44
    23
    21
    14
    12
    30
    70
    Units: odds of nocturnal voids
        arithmetic mean (confidence interval 95%)
    1.395 (0.717 to 2.715)
    3.398 (1.150 to 10.043)
    1.928 (0.721 to 5.155)
    0.877 (0.286 to 2.688)
    1.039 (0.302 to 3.569)
    1.489 (0.638 to 3.474)
    1.503 (0.806 to 2.803)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.85 [45]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.928
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 2.003
    Notes
    [45] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.15 [46]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.261
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.745
         upper limit
    		 6.862
    Notes
    [46] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.632 [47]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.283
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.462
         upper limit
    		 3.566
    Notes
    [47] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.363 [48]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.583
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.183
         upper limit
    		 1.863
    Notes
    [48] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.555 [49]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.691
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.203
         upper limit
    		 2.359
    Notes
    [49] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.984 [50]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.991
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.408
         upper limit
    		 2.405
    Notes
    [50] - Threshold for significance at 0.05 level.

    Secondary: Responder Rate in Nocturnal Voids at Week 12

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    End point title
    		 Responder Rate in Nocturnal Voids at Week 12 [51]
    End point description
    Defined as 50% reduction in nocturnal voids from baseline. Adjusted visit-specific estimated odds of at least 50% reduction mean number of nocturnal voids are estimated using a baseline value of 2. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    40
    19
    19
    14
    11
    29
    69
    Units: odds of nocturnal voids
        arithmetic mean (confidence interval 95%)
    3.914 (1.830 to 8.370)
    1.891 (0.693 to 5.163)
    1.824 (0.694 to 4.795)
    0.854 (0.279 to 2.611)
    1.400 (0.401 to 4.893)
    1.395 (0.611 to 3.181)
    1.590 (0.844 to 2.993)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.046 [52]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.462
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.017
         upper limit
    		 5.961
    Notes
    [52] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.745 [53]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.418
         upper limit
    		 3.386
    Notes
    [53] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.79 [54]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.147
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.417
         upper limit
    		 3.155
    Notes
    [54] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.293 [55]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.537
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.169
         upper limit
    		 1.71
    Notes
    [55] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.843 [56]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.881
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.252
         upper limit
    		 3.076
    Notes
    [56] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.763 [57]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.877
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.375
         upper limit
    		 2.053
    Notes
    [57] - Threshold for significance at 0.05 level.

    Secondary: Responder Rate in Nocturnal Voids During 12 Weeks of Treatment

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    End point title
    		 Responder Rate in Nocturnal Voids During 12 Weeks of Treatment [58]
    End point description
    Defined as 50% reduction in nocturnal voids from baseline. Estimated odds of at least 50% reduction in the aggregated mean number of nocturnal voids for a subject with 2 nocturnal voids at baseline are presented in this endpoint. The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    During 12 weeks of treatment
    Notes
    [58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    60
    27
    24
    14
    13
    34
    87
    Units: odds of nocturnal voids
        arithmetic mean (confidence interval 95%)
    1.129 (0.808 to 1.753)
    1.095 (0.772 to 1.661)
    1.032 (0.711 to 1.543)
    0.934 (0.597 to 1.378)
    0.887 (0.555 to 1.253)
    0.849 (0.534 to 1.187)
    0.834 (0.514 to 1.180)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 500 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.422
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.868
         upper limit
    		 2.597
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.373
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.905
         upper limit
    		 2.45
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.284
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.927
         upper limit
    		 2.264
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.145
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.957
         upper limit
    		 1.896
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.079
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.972
         upper limit
    		 1.638
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.023
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.991
         upper limit
    		 1.313

    Secondary: Change From Baseline in Mean NI Diary Total Score at Week 1

    		 Close Top of page
    End point title
    		 Change From Baseline in Mean NI Diary Total Score at Week 1 [59]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall quality of life (QoL) impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    Notes
    [59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    55
    23
    24
    14
    12
    31
    83
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    -7.55 (-11.67 to -3.43)
    -21.91 (-28.15 to -15.68)
    -10.90 (-17.17 to -4.63)
    -8.93 (-17.15 to -0.72)
    -9.68 (-18.41 to -0.94)
    -8.75 (-14.27 to -3.23)
    -8.07 (-11.48 to -4.65)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8463 [60]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.75
         upper limit
    		 5.78
    Notes
    [60] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001 [61]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -13.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.89
         upper limit
    		 -6.81
    Notes
    [61] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4355 [62]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -2.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.99
         upper limit
    		 4.32
    Notes
    [62] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8483 [63]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.79
         upper limit
    		 8.06
    Notes
    [63] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7336 [64]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -1.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.91
         upper limit
    		 7.69
    Notes
    [64] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8347 [65]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.15
         upper limit
    		 5.78
    Notes
    [65] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean NI Diary Total Score at Week 4

    		 Close Top of page
    End point title
    		 Change From Baseline in Mean NI Diary Total Score at Week 4 [66]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    Notes
    [66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    53
    24
    22
    13
    13
    31
    78
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    -12.62 (-16.89 to -8.35)
    -17.44 (-23.80 to -11.08)
    -14.37 (-20.96 to -7.78)
    -11.23 (-19.82 to -2.65)
    -22.23 (-31.11 to -13.35)
    -13.29 (-19.00 to -7.58)
    -14.20 (-17.77 to -10.64)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5695 [67]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    1.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.9
         upper limit
    		 7.07
    Notes
    [67] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3784 [68]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -3.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.46
         upper limit
    		 3.99
    Notes
    [68] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9653 [69]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.67
         upper limit
    		 7.34
    Notes
    [69] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5304 [70]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    2.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.35
         upper limit
    		 12.29
    Notes
    [70] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0968 [71]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -8.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.51
         upper limit
    		 1.46
    Notes
    [71] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7885 [72]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.79
         upper limit
    		 7.62
    Notes
    [72] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean NI Diary Total Score at Week 8

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    End point title
    		 Change From Baseline in Mean NI Diary Total Score at Week 8 [73]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    50
    24
    23
    14
    11
    30
    79
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    -16.03 (-20.49 to -11.57)
    -23.22 (-29.79 to -16.64)
    -15.10 (-21.85 to -8.35)
    -12.04 (-20.77 to -3.32)
    -19.23 (-28.62 to -9.83)
    -14.11 (-20.00 to -8.22)
    -14.83 (-18.50 to -11.16)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6792 [74]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.89
         upper limit
    		 4.5
    Notes
    [74] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0276 [75]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -8.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.84
         upper limit
    		 -0.93
    Notes
    [75] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9445 [76]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.97
         upper limit
    		 7.42
    Notes
    [76] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5637 [77]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    2.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.71
         upper limit
    		 12.28
    Notes
    [77] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.387 [78]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -4.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.39
         upper limit
    		 5.6
    Notes
    [78] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8373 [79]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.19
         upper limit
    		 7.63
    Notes
    [79] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean NI Diary Total Score at Week 12

    		 Close Top of page
    End point title
    		 Change From Baseline in Mean NI Diary Total Score at Week 12 [80]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Total Score are estimated using a baseline value of 40. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    50
    22
    21
    14
    12
    31
    77
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    -16.92 (-21.66 to -12.18)
    -24.44 (-31.52 to -17.35)
    -14.68 (-21.94 to -7.42)
    -10.13 (-19.37 to -0.88)
    -22.59 (-32.46 to -12.71)
    -17.18 (-23.39 to -10.96)
    -17.45 (-21.36 to -13.53)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8646 [81]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.54
         upper limit
    		 6.59
    Notes
    [81] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.087 [82]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -6.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15
         upper limit
    		 1.02
    Notes
    [82] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.51 [83]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    2.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.5
         upper limit
    		 11.04
    Notes
    [83] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1535 [84]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    7.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.75
         upper limit
    		 17.39
    Notes
    [84] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3369 [85]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -5.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.66
         upper limit
    		 5.38
    Notes
    [85] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9417 [86]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.05
         upper limit
    		 7.59
    Notes
    [86] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment

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    End point title
    		 Change From Baseline in Aggregated Mean NI Diary Total Score During 12 Weeks of Treatment [87]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). The NI Diary Total Scores are calculated by summing the 11 core items. Responses are scored from 0 to 4 (lowest to highest impact). The NI Diary Total is standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the mean over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits. Level estimated for baseline value of mean NI Diary Total Score equal to 40 is presented in this endpoint. The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, during 12 weeks of treatment
    Notes
    [87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    60
    27
    24
    14
    13
    34
    87
    Units: score on a scale
        median (confidence interval 95%)
    -12.40 (-14.71 to -8.59)
    -12.69 (-15.07 to -10.53)
    -12.75 (-15.16 to -10.57)
    -12.77 (-15.21 to -10.59)
    -12.77 (-15.23 to -10.54)
    -12.78 (-15.18 to -10.50)
    -12.77 (-15.18 to -10.47)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Median Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.41
         upper limit
    		 5.47
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Median Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.43
         upper limit
    		 1.19
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Median Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.5
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Median Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0.15
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Median Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.01
         upper limit
    		 0.05
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Median difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.01

    Secondary: Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment

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    End point title
    		 Percentage of Nights With at Most One Nocturnal Void During 12 Weeks of Treatment [88]
    End point description
    The percentages of nights during the treatment period with at most one nocturnal void are presented in this endpoint. Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    During 12 weeks of treatment
    Notes
    [88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    58
    27
    24
    14
    13
    33
    84
    Units: percentage of nights
        arithmetic mean (confidence interval 95%)
    67.2 (58.2 to 76.2)
    77.5 (64.9 to 90.2)
    64.5 (51.0 to 78.0)
    55.3 (38.3 to 72.3)
    73.2 (55.1 to 91.2)
    61.4 (49.3 to 73.5)
    62.0 (53.8 to 70.2)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3328 [89]
    Method
    		 ANCOVA
    Parameter type
    		 Mean Difference
    Point estimate
    5.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.3
         upper limit
    		 15.7
    Notes
    [89] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0255 [90]
    Method
    		 ANCOVA
    Parameter type
    		 Mean Difference
    Point estimate
    15.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.9
         upper limit
    		 29.2
    Notes
    [90] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7296 [91]
    Method
    		 ANCOVA
    Parameter type
    		 Mean Difference
    Point estimate
    2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.7
         upper limit
    		 16.7
    Notes
    [91] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4586 [92]
    Method
    		 ANCOVA
    Parameter type
    		 Mean Difference
    Point estimate
    -6.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.5
         upper limit
    		 11.1
    Notes
    [92] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2327 [93]
    Method
    		 ANCOVA
    Parameter type
    		 Mean Difference
    Point estimate
    11.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.2
         upper limit
    		 29.5
    Notes
    [93] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.924 [94]
    Method
    		 ANCOVA
    Parameter type
    		 Mean Difference
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.3
         upper limit
    		 12.1
    Notes
    [94] - Threshold for significance at 0.05 level.

    Secondary: Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment

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    End point title
    		 Percentage of Nights With No Nocturnal Voids During 12 Weeks of Treatment [95]
    End point description
    The percentages of nights during the treatment period with complete response, i.e. no nocturnal voids are presented in this endpoint. Level estimated for baseline value of mean number of nocturnal voids equal to 2 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    During 12 weeks of treatment
    Notes
    [95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    58
    27
    24
    14
    13
    33
    84
    Units: percentage of nights
        arithmetic mean (confidence interval 95%)
    23.3 (16.3 to 30.3)
    28.8 (19.0 to 38.6)
    17.3 (6.8 to 27.8)
    12.9 (-0.3 to 26.1)
    14.8 (0.8 to 28.8)
    21.5 (12.1 to 30.9)
    23.0 (16.6 to 29.4)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 500 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9499 [96]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.9
         upper limit
    		 8.5
    Notes
    [96] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2842 [97]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference
    Point estimate
    5.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 16.4
    Notes
    [97] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.31 [98]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference
    Point estimate
    -5.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.8
         upper limit
    		 5.4
    Notes
    [98] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1499 [99]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference
    Point estimate
    -10.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.9
         upper limit
    		 3.7
    Notes
    [99] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2571 [100]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference
    Point estimate
    -8.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.5
         upper limit
    		 6
    Notes
    [100] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7629 [101]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference
    Point estimate
    -1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.4
         upper limit
    		 8.3
    Notes
    [101] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean NI Diary Overall Impact Score at Week 1

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    End point title
    		 Change From Baseline in Mean NI Diary Overall Impact Score at Week 1 [102]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40 The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    Notes
    [102] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    55
    23
    24
    14
    12
    31
    83
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    -10.98 (-16.40 to -5.56)
    -30.39 (-38.62 to -22.17)
    -15.51 (-23.85 to -7.17)
    -11.77 (-22.69 to -0.85)
    -2.79 (-14.29 to 8.70)
    -12.26 (-19.57 to -4.95)
    -13.46 (-17.89 to -9.03)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4846 [103]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.5
         upper limit
    		 9.46
    Notes
    [103] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0004 [104]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -16.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.26
         upper limit
    		 -7.6
    Notes
    [104] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6685 [105]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -2.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.47
         upper limit
    		 7.37
    Notes
    [105] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7772 [106]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    1.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.07
         upper limit
    		 13.46
    Notes
    [106] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0895 [107]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    10.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.66
         upper limit
    		 23
    Notes
    [107] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.782 [108]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.34
         upper limit
    		 9.74
    Notes
    [108] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean NI Diary Overall Impact Score at Week 4

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    End point title
    		 Change From Baseline in Mean NI Diary Overall Impact Score at Week 4 [109]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    Notes
    [109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    53
    24
    22
    13
    13
    31
    78
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    -22.17 (-28.25 to -16.09)
    -26.07 (-35.09 to -17.05)
    -19.35 (-28.80 to -9.90)
    -18.36 (-30.66 to -6.07)
    -17.95 (-30.50 to -5.41)
    -21.40 (-29.54 to -13.26)
    -21.75 (-26.74 to -16.77)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9175 [110]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -0.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.25
         upper limit
    		 7.42
    Notes
    [110] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4098 [111]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -4.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.62
         upper limit
    		 5.98
    Notes
    [111] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6566 [112]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    2.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.25
         upper limit
    		 13.06
    Notes
    [112] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6144 [113]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    3.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.85
         upper limit
    		 16.63
    Notes
    [113] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5798 [114]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.71
         upper limit
    		 17.31
    Notes
    [114] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9417 [115]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    0.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.17
         upper limit
    		 9.88
    Notes
    [115] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean NI Diary Overall Impact Score at Week 8

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    End point title
    		 Change From Baseline in Mean NI Diary Overall Impact Score at Week 8 [116]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [116] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    50
    24
    23
    14
    11
    30
    79
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    -28.13 (-34.76 to -21.50)
    -34.97 (-44.69 to -25.25)
    -21.71 (-31.80 to -11.62)
    -19.03 (-32.06 to -6.00)
    -23.84 (-37.71 to -9.96)
    -20.70 (-29.45 to -11.94)
    -25.32 (-30.69 to -19.95)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5148 [117]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -2.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.31
         upper limit
    		 5.68
    Notes
    [117] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0879 [118]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    -9.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.75
         upper limit
    		 1.44
    Notes
    [118] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5335 [119]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    3.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.79
         upper limit
    		 15
    Notes
    [119] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3787 [120]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    6.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.76
         upper limit
    		 20.34
    Notes
    [120] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8448 [121]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    1.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.41
         upper limit
    		 16.38
    Notes
    [121] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3751 [122]
    Method
    		 MMRM
    Parameter type
    		 Mean difference
    Point estimate
    4.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.63
         upper limit
    		 14.87
    Notes
    [122] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean NI Diary Overall Impact Score at Week 12

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    End point title
    		 Change From Baseline in Mean NI Diary Overall Impact Score at Week 12 [123]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NI Diary Overall Impact Score are estimated using a baseline value of 40. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [123] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    50
    22
    21
    14
    12
    31
    77
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    -30.47 (-37.49 to -23.45)
    -36.76 (-47.18 to -26.34)
    -20.84 (-31.65 to -10.02)
    -15.32 (-29.10 to -1.54)
    -28.89 (-43.40 to -14.39)
    -27.13 (-36.35 to -17.91)
    -30.03 (-35.74 to -24.33)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9245 [124]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.43
         upper limit
    		 8.57
    Notes
    [124] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2657 [125]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -6.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.59
         upper limit
    		 5.15
    Notes
    [125] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1383 [126]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    9.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.99
         upper limit
    		 21.38
    Notes
    [126] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0523 [127]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    14.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 29.59
    Notes
    [127] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8855 [128]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.47
         upper limit
    		 16.75
    Notes
    [128] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5972 [129]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    2.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.91
         upper limit
    		 13.72
    Notes
    [129] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment

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    End point title
    		 Change From Baseline in Aggregated Mean NI Diary Overall Impact Score During 12 Weeks of Treatment [130]
    End point description
    The NI Diary is a 12-item questionnaire with 11 core items (Q1-Q11) and an overall QoL impact question (Q12). For the overall impact question (Q12), response options range from 0 (not at all) to 4 (a great deal). The NI Diary Overall Impact Scores are standardised from 0 to 100 (lowest to highest impact). The score at each visit was calculated as the average over the three consecutive 24 hour periods just prior to the respective visit. The visit-specific means were aggregated into a mean of current and preceding visits. Level estimated for baseline value of mean NI Diary Overall Impact Score equal to 40 is presented in this endpoint. The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, during 12 weeks of treatment
    Notes
    [130] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    60
    27
    24
    14
    13
    34
    87
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    -6.50 (-10.57 to -2.85)
    -6.25 (-9.78 to -3.03)
    -6.11 (-9.49 to -2.90)
    -6.00 (-9.28 to -2.70)
    -5.98 (-9.29 to -2.58)
    -5.97 (-9.32 to -2.57)
    -5.96 (-9.42 to -2.49)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.09
         upper limit
    		 2.28
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.3
         upper limit
    		 0.75
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.44
         upper limit
    		 0.33
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.92
         upper limit
    		 0.07
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.48
         upper limit
    		 0.02
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0

    Secondary: Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1

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    End point title
    		 Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 1 [131]
    End point description
    The PGI-I is a 1-item questionnaire designed to assess the patient’s impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse). Visit-specific PGI-I in urinary symptoms is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Week 1
    Notes
    [131] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    53
    23
    24
    14
    11
    33
    81
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    2.475 (2.261 to 2.689)
    2.045 (1.723 to 2.367)
    2.708 (2.385 to 3.031)
    2.786 (2.363 to 3.209)
    2.781 (2.316 to 3.245)
    2.758 (2.482 to 3.033)
    2.745 (2.571 to 2.919)
    Statistical analysis title
    		 FE 201836 500 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 500 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.055 [132]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.545
         upper limit
    		 0.006
    Notes
    [132] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0002 [133]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.066
         upper limit
    		 -0.335
    Notes
    [133] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.844 [134]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.037
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.404
         upper limit
    		 0.33
    Notes
    [134] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.861 [135]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.041
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.417
         upper limit
    		 0.498
    Notes
    [135] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8871 [136]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.036
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.46
         upper limit
    		 0.532
    Notes
    [136] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 µg, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9396 [137]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.013
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.313
         upper limit
    		 0.338
    Notes
    [137] - Threshold for significance at 0.05 level.

    Secondary: Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4

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    End point title
    		 Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 4 [138]
    End point description
    The PGI-I is a 1-item questionnaire designed to assess the patient’s impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse). Visit-specific PGI-I in urinary symptoms is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Week 4
    Notes
    [138] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    53
    24
    20
    12
    13
    30
    77
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    2.121 (1.866 to 2.376)
    2.191 (1.813 to 2.569)
    2.447 (2.039 to 2.855)
    2.521 (1.995 to 3.047)
    2.385 (1.859 to 2.910)
    2.582 (2.244 to 2.921)
    2.596 (2.386 to 2.806)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 500 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005 [139]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.475
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.806
         upper limit
    		 -0.145
    Notes
    [139] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0665 [140]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.405
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.837
         upper limit
    		 0.028
    Notes
    [140] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5245 [141]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.149
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.608
         upper limit
    		 0.31
    Notes
    [141] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7947 [142]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.075
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.642
         upper limit
    		 0.492
    Notes
    [142] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4625 [143]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.211
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.777
         upper limit
    		 0.355
    Notes
    [143] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9465 [144]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.014
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.412
         upper limit
    		 0.385
    Notes
    [144] - Threshold for significance at 0.05 level.

    Secondary: Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8

    		 Close Top of page
    End point title
    		 Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 8 [145]
    End point description
    The PGI-I is a 1-item questionnaire designed to assess the patient’s impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse). Visit-specific PGI-I in urinary symptoms is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Week 8
    Notes
    [145] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    49
    24
    21
    14
    11
    28
    78
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    1.843 (1.572 to 2.113)
    1.887 (1.493 to 2.281)
    2.528 (2.109 to 2.947)
    2.286 (1.761 to 2.811)
    2.155 (1.587 to 2.723)
    2.273 (1.917 to 2.629)
    2.573 (2.355 to 2.791)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [146]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.078
         upper limit
    		 -0.383
    Notes
    [146] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003 [147]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.686
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.137
         upper limit
    		 -0.236
    Notes
    [147] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.852 [148]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.045
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.517
         upper limit
    		 0.427
    Notes
    [148] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3205 [149]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.287
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.856
         upper limit
    		 0.281
    Notes
    [149] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1769 [150]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.418
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.026
         upper limit
    		 0.19
    Notes
    [150] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1584 [151]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.717
         upper limit
    		 0.118
    Notes
    [151] - Threshold for significance at 0.05 level.

    Secondary: Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12

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    End point title
    		 Patient Global Impression of Improvement (PGI-I) Urinary Symptoms Scores at Week 12 [152]
    End point description
    The PGI-I is a 1-item questionnaire designed to assess the patient’s impression of changes in urinary symptoms. The PGI-I was scored from 1 (very much better) to 7 (very much worse). Visit-specific PGI-I in urinary symptoms is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [152] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    46
    23
    18
    13
    12
    31
    72
    Units: score on a scale
        arithmetic mean (confidence interval 95%)
    1.667 (1.357 to 1.977)
    1.671 (1.224 to 2.119)
    2.656 (2.167 to 3.146)
    2.452 (1.855 to 3.049)
    1.678 (1.052 to 2.304)
    2.384 (1.994 to 2.774)
    2.490 (2.240 to 2.740)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [153]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.822
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.22
         upper limit
    		 -0.424
    Notes
    [153] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0019 [154]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.818
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.331
         upper limit
    		 -0.306
    Notes
    [154] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.551 [155]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.167
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.383
         upper limit
    		 0.716
    Notes
    [155] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9086 [156]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.038
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.685
         upper limit
    		 0.61
    Notes
    [156] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0185 [157]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.812
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.486
         upper limit
    		 -0.138
    Notes
    [157] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6537 [158]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.106
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.569
         upper limit
    		 0.357
    Notes
    [158] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1

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    End point title
    		 Change From Baseline in Patient Global Impression of Severity (PGI-S) Scores at Week 1 [159]
    End point description
    The PGI-S is a 1-item questionnaire designed to assess patient’s impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe). Change from baseline in visit-specific PGI-S is presented in this endpoint. Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    Notes
    [159] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    53
    23
    24
    14
    10
    28
    80
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -0.739 (-0.927 to -0.552)
    -0.970 (-1.253 to -0.688)
    -0.811 (-1.094 to -0.529)
    -0.643 (-1.012 to -0.273)
    -0.417 (-0.840 to 0.007)
    -0.719 (-0.984 to -0.454)
    -0.593 (-0.746 to -0.440)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.235 [160]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.146
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.388
         upper limit
    		 0.096
    Notes
    [160] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0215 [161]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.377
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.699
         upper limit
    		 -0.056
    Notes
    [161] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1818 [162]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.218
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.54
         upper limit
    		 0.103
    Notes
    [162] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8063 [163]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.45
         upper limit
    		 0.35
    Notes
    [163] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4414 [164]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.176
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.274
         upper limit
    		 0.627
    Notes
    [164] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4179 [165]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.126
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.432
         upper limit
    		 0.18
    Notes
    [165] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in PGI-S Scores at Week 4

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    End point title
    		 Change From Baseline in PGI-S Scores at Week 4 [166]
    End point description
    The PGI-S is a 1-item questionnaire designed to assess patient’s impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe). Change from baseline in visit-specific PGI-S is presented in this endpoint. Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    Notes
    [166] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    52
    23
    20
    12
    12
    27
    75
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -0.837 (-1.015 to -0.659)
    -1.025 (-1.292 to -0.758)
    -0.798 (-1.081 to -0.516)
    -0.749 (-1.115 to -0.383)
    -0.656 (-1.033 to -0.278)
    -0.936 (-1.189 to -0.684)
    -0.898 (-1.045 to -0.750)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6042 [167]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.061
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.17
         upper limit
    		 0.292
    Notes
    [167] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4114 [168]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.127
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.432
         upper limit
    		 0.177
    Notes
    [168] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5394 [169]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.099
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.219
         upper limit
    		 0.418
    Notes
    [169] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.459 [170]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.149
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.246
         upper limit
    		 0.544
    Notes
    [170] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2397 [171]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.242
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.163
         upper limit
    		 0.647
    Notes
    [171] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7954 [172]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.039
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.332
         upper limit
    		 0.254
    Notes
    [172] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in PGI-S Scores at Week 8

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    End point title
    		 Change From Baseline in PGI-S Scores at Week 8 [173]
    End point description
    The PGI-S is a 1-item questionnaire designed to assess patient’s impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe). Change from baseline in visit-specific PGI-S is presented in this endpoint. Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [173] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    48
    23
    21
    14
    11
    25
    76
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -1.132 (-1.322 to -0.942)
    -1.410 (-1.688 to -1.132)
    -0.825 (-1.114 to -0.536)
    -0.643 (-1.004 to -0.281)
    -0.816 (-1.215 to -0.418)
    -1.013 (-1.279 to -0.747)
    -0.800 (-0.953 to -0.647)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0077 [174]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.332
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.576
         upper limit
    		 -0.089
    Notes
    [174] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0002 [175]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.927
         upper limit
    		 -0.293
    Notes
    [175] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8778 [176]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.026
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.352
         upper limit
    		 0.301
    Notes
    [176] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4309 [177]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.157
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.235
         upper limit
    		 0.549
    Notes
    [177] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9392 [178]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.017
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.444
         upper limit
    		 0.411
    Notes
    [178] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1734 [179]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.213
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.521
         upper limit
    		 0.094
    Notes
    [179] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in PGI-S Scores at Week 12

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    End point title
    		 Change From Baseline in PGI-S Scores at Week 12 [180]
    End point description
    The PGI-S is a 1-item questionnaire designed to assess patient’s impression of disease severity. The PGI-S was scored from 1 (none) to 4 (severe). Change from baseline in visit-specific PGI-S is presented in this endpoint. Level estimated for baseline value of PGI-S equal to 3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [180] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    45
    22
    18
    13
    12
    27
    70
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -1.181 (-1.383 to -0.979)
    -1.338 (-1.630 to -1.045)
    -0.894 (-1.208 to -0.579)
    -0.638 (-1.020 to -0.257)
    -1.168 (-1.571 to -0.764)
    -1.041 (-1.312 to -0.770)
    -0.853 (-1.016 to -0.690)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0133 [181]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.328
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.587
         upper limit
    		 -0.069
    Notes
    [181] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0048 [182]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.484
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.819
         upper limit
    		 -0.15
    Notes
    [182] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8223 [183]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.395
         upper limit
    		 0.314
    Notes
    [183] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3083 [184]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.215
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.63
    Notes
    [184] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1556 [185]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.315
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.75
         upper limit
    		 0.121
    Notes
    [185] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2423 [186]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.188
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.504
         upper limit
    		 0.128
    Notes
    [186] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1

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    End point title
    		 Change From Baseline in Hsu 5-point Likert Bother Scale at Week 1 [187]
    End point description
    The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely). Change from baseline in visit-specific Hsu Bother is presented in this endpoint. Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    Notes
    [187] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    50
    23
    24
    14
    9
    30
    70
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -0.649 (-0.922 to -0.376)
    -1.072 (-1.441 to -0.703)
    -0.748 (-1.125 to -0.370)
    -0.458 (-0.942 to 0.026)
    -0.346 (-0.955 to 0.262)
    -0.376 (-0.714 to -0.039)
    -0.570 (-0.799 to -0.341)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6381 [188]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.079
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.409
         upper limit
    		 0.251
    Notes
    [188] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0221 [189]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.502
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.931
         upper limit
    		 -0.073
    Notes
    [189] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4112 [190]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.177
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.602
         upper limit
    		 0.247
    Notes
    [190] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6761 [191]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.112
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.416
         upper limit
    		 0.64
    Notes
    [191] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4898 [192]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.224
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.414
         upper limit
    		 0.861
    Notes
    [192] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3311 [193]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.194
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.198
         upper limit
    		 0.585
    Notes
    [193] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4

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    End point title
    		 Change From Baseline in Hsu 5-point Likert Bother Scale at Week 4 [194]
    End point description
    The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely). Change from baseline in visit-specific Hsu Bother is presented in this endpoint. Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    Notes
    [194] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    47
    23
    22
    13
    8
    27
    68
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -0.896 (-1.161 to -0.630)
    -0.940 (-1.294 to -0.586)
    -0.712 (-1.083 to -0.340)
    -0.606 (-1.079 to -0.132)
    -1.096 (-1.698 to -0.493)
    -0.861 (-1.193 to -0.530)
    -0.665 (-0.885 to -0.445)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1583 [195]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.551
         upper limit
    		 0.09
    Notes
    [195] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1884 [196]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.275
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.685
         upper limit
    		 0.136
    Notes
    [196] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8256 [197]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.047
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.463
         upper limit
    		 0.369
    Notes
    [197] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8198 [198]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.059
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.455
         upper limit
    		 0.574
    Notes
    [198] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    76
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1793 [199]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.431
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.061
         upper limit
    		 0.199
    Notes
    [199] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3155 [200]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.196
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.581
         upper limit
    		 0.189
    Notes
    [200] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8

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    End point title
    		 Change From Baseline in Hsu 5-point Likert Bother Scale at Week 8 [201]
    End point description
    The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely). Change from baseline in visit-specific Hsu Bother is presented in this endpoint. Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [201] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    40
    24
    23
    14
    7
    27
    71
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -0.972 (-1.273 to -0.672)
    -1.044 (-1.423 to -0.664)
    -0.991 (-1.389 to -0.594)
    -0.499 (-1.001 to 0.004)
    -1.012 (-1.691 to -0.333)
    -0.881 (-1.240 to -0.522)
    -0.731 (-0.968 to -0.495)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.183 [202]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.241
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.596
         upper limit
    		 0.114
    Notes
    [202] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1618 [203]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.313
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.751
         upper limit
    		 0.126
    Notes
    [203] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2519 [204]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.706
         upper limit
    		 0.186
    Notes
    [204] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4044 [205]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.232
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.316
         upper limit
    		 0.781
    Notes
    [205] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4348 [206]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.986
         upper limit
    		 0.426
    Notes
    [206] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4786 [207]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.565
         upper limit
    		 0.266
    Notes
    [207] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12

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    End point title
    		 Change From Baseline in Hsu 5-point Likert Bother Scale at Week 12 [208]
    End point description
    The Hsu 5-point Likert Bother scale is a questionnaire designed to assess the subjective bothersomeness and functional disruptiveness of nocturia. The Hsu 5 point Likert Bother Scale was scored from 0 (not at all) to 4 (extremely). Change from baseline in visit-specific Hsu Bother is presented in this endpoint. Level estimated for baseline value of Hsu Bother equal to 3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [208] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    45
    22
    21
    14
    8
    28
    67
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -0.992 (-1.306 to -0.679)
    -1.249 (-1.663 to -0.834)
    -0.700 (-1.132 to -0.267)
    -0.880 (-1.416 to -0.343)
    -0.974 (-1.676 to -0.272)
    -0.921 (-1.303 to -0.540)
    -0.769 (-1.027 to -0.511)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2412 [209]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.223
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.598
         upper limit
    		 0.151
    Notes
    [209] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0501 [210]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.959
         upper limit
    		 0
    Notes
    [210] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7788 [211]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.069
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.417
         upper limit
    		 0.556
    Notes
    [211] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7111 [212]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.111
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.698
         upper limit
    		 0.477
    Notes
    [212] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5816 [213]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.205
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.937
         upper limit
    		 0.527
    Notes
    [213] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4981 [214]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.152
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.595
         upper limit
    		 0.29
    Notes
    [214] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in ISI at Week 4

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    End point title
    		 Change From Baseline in ISI at Week 4 [215]
    End point description
    The ISI is a 7-item questionnaire which comprises of four `sleep-related' items and three `wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia). Change from baseline in visit-specific ISI is presented in this endpoint. Level estimated for baseline value of ISI equal to 15 is presented in this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    Notes
    [215] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    47
    24
    22
    13
    8
    27
    68
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -6.589 (-8.046 to -5.133)
    -6.652 (-8.689 to -4.616)
    -5.630 (-7.772 to -3.487)
    -5.428 (-8.200 to -2.656)
    -4.510 (-7.996 to -1.023)
    -6.372 (-8.291 to -4.452)
    -5.277 (-6.493 to -4.061)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1733 [216]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -1.313
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.207
         upper limit
    		 0.582
    Notes
    [216] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2538 [217]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -1.375
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.745
         upper limit
    		 0.994
    Notes
    [217] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7782 [218]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.353
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.818
         upper limit
    		 2.113
    Notes
    [218] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9218 [219]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.151
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.182
         upper limit
    		 2.88
    Notes
    [219] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    76
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6823 [220]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.767
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.923
         upper limit
    		 4.457
    Notes
    [220] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3436 [221]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -1.095
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.369
         upper limit
    		 1.179
    Notes
    [221] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in ISI at Week 8

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    End point title
    		 Change From Baseline in ISI at Week 8 [222]
    End point description
    The ISI is a 7-item questionnaire which comprises of four `sleep-related' items and three `wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia). Change from baseline in visit-specific ISI is presented in this endpoint. Level estimated for baseline value of ISI equal to 15 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [222] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    40
    24
    23
    14
    7
    28
    71
    Units: units on a scale
        least squares mean (confidence interval 95%)
    -7.643 (-9.140 to -6.147)
    -8.091 (-10.116 to -6.067)
    -6.693 (-8.799 to -4.588)
    -6.959 (-9.668 to -4.250)
    -5.707 (-9.283 to -2.131)
    -7.167 (-9.055 to -5.280)
    -6.408 (-7.603 to -5.213)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2042 [223]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -1.235
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.146
         upper limit
    		 0.676
    Notes
    [223] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1591 [224]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -1.683
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.031
         upper limit
    		 0.665
    Notes
    [224] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8168 [225]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.285
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.708
         upper limit
    		 2.138
    Notes
    [225] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7148 [226]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.551
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.517
         upper limit
    		 2.416
    Notes
    [226] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7141 [227]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.701
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.066
         upper limit
    		 4.468
    Notes
    [227] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5041 [228]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.759
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.995
         upper limit
    		 1.477
    Notes
    [228] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in ISI at Week 12

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    End point title
    		 Change From Baseline in ISI at Week 12 [229]
    End point description
    The ISI is a 7-item questionnaire which comprises of four `sleep-related' items and three `wake-related' items. Each item is rated on a 0-4 scale and the total score ranges from 0 to 28 (higher score suggests more severe insomnia). Change from baseline in visit-specific ISI is presented in this endpoint. Level estimated for baseline value of ISI equal to 15 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [229] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    45
    22
    21
    14
    8
    27
    67
    Units: score on a scale
        least squares mean (confidence interval 95%)
    -7.807 (-9.427 to -6.188)
    -9.329 (-11.619 to -7.040)
    -6.355 (-8.733 to -3.977)
    -6.193 (-9.195 to -3.191)
    -5.002 (-8.865 to -1.138)
    -7.908 (-10.016 to -5.800)
    -6.678 (-8.018 to -5.338)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2896 [230]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -1.129
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.226
         upper limit
    		 0.967
    Notes
    [230] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0498 [231]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -2.652
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.301
         upper limit
    		 -0.003
    Notes
    [231] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8159 [232]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.323
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.409
         upper limit
    		 3.055
    Notes
    [232] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7719 [233]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.485
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.809
         upper limit
    		 3.779
    Notes
    [233] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4193 [234]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    1.676
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.407
         upper limit
    		 5.76
    Notes
    [234] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3333 [235]
    Method
    		 MMRM
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.73
         upper limit
    		 1.27
    Notes
    [235] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1

    		 Close Top of page
    End point title
    		 Change From Baseline in Mean Duration of First Undisturbed Sleep Period (FUSP) at Week 1 [236]
    End point description
    The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occured. The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min). The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    Notes
    [236] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    54
    24
    24
    14
    11
    33
    80
    Units: minutes
        least squares mean (confidence interval 95%)
    122.9 (86.2 to 159.7)
    187.0 (132.3 to 241.7)
    106.0 (49.6 to 162.4)
    91.7 (18.7 to 164.8)
    82.9 (2.5 to 163.4)
    51.3 (3.9 to 98.7)
    81.1 (50.8 to 111.4)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0853 [237]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    41.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.9
         upper limit
    		 89.6
    Notes
    [237] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001 [238]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    105.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 43.4
         upper limit
    		 168.4
    Notes
    [238] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4418 [239]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    24.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.8
         upper limit
    		 88.6
    Notes
    [239] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7902 [240]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    10.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -68.2
         upper limit
    		 89.6
    Notes
    [240] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9664 [241]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -84.2
         upper limit
    		 87.9
    Notes
    [241] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2977 [242]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -29.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -85.9
         upper limit
    		 26.4
    Notes
    [242] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean Duration of FUSP at Week 4

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    End point title
    		 Change From Baseline in Mean Duration of FUSP at Week 4 [243]
    End point description
    The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred. The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min). The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    Notes
    [243] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    50
    22
    21
    12
    12
    31
    76
    Units: minutes
        arithmetic mean (confidence interval 95%)
    164.5 (127.9 to 201.0)
    211.0 (156.3 to 265.7)
    132.3 (75.2 to 189.4)
    89.5 (15.1 to 163.9)
    122.0 (46.8 to 197.3)
    95.5 (48.6 to 142.5)
    150.2 (120.4 to 180.0)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    126
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5523 [244]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    14.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33
         upper limit
    		 61.5
    Notes
    [244] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0556 [245]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    60.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 123
    Notes
    [245] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5837 [246]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -17.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -82
         upper limit
    		 46.3
    Notes
    [246] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1363 [247]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -60.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -140.7
         upper limit
    		 19.3
    Notes
    [247] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4938 [248]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -28.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -109.1
         upper limit
    		 52.8
    Notes
    [248] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0535 [249]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -54.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -110.2
         upper limit
    		 0.8
    Notes
    [249] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean Duration of FUSP at Week 8

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    End point title
    		 Change From Baseline in Mean Duration of FUSP at Week 8 [250]
    End point description
    The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred. The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min). The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 8
    Notes
    [250] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    44
    23
    21
    14
    12
    30
    70
    Units: minutes
        arithmetic mean (confidence interval 95%)
    160.4 (112.4 to 208.3)
    225.4 (157.9 to 293.0)
    190.2 (118.9 to 261.6)
    136.8 (48.3 to 225.4)
    163.2 (68.7 to 257.8)
    164.3 (104.9 to 223.7)
    161.0 (122.6 to 199.5)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9829 [251]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -62.2
         upper limit
    		 60.9
    Notes
    [251] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1038 [252]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    64.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.3
         upper limit
    		 142.1
    Notes
    [252] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4764 [253]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    29.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -51.4
         upper limit
    		 109.8
    Notes
    [253] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6204 [254]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -24.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -120.5
         upper limit
    		 72
    Notes
    [254] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.966 [255]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -100.1
         upper limit
    		 104.6
    Notes
    [255] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9275 [256]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -67.4
         upper limit
    		 73.9
    Notes
    [256] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean Duration of FUSP at Week 12

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    End point title
    		 Change From Baseline in Mean Duration of FUSP at Week 12 [257]
    End point description
    The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred. The duration of FUSP at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in FUSP are estimated using a baseline value of 180 (min). The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [257] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    40
    19
    19
    14
    11
    29
    69
    Units: minutes
        arithmetic mean (confidence interval 95%)
    178.5 (132.5 to 224.5)
    160.0 (93.3 to 226.6)
    180.7 (112.2 to 249.2)
    111.5 (29.7 to 193.2)
    141.1 (51.3 to 230.9)
    166.2 (110.5 to 221.8)
    162.8 (126.9 to 198.7)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5964 [258]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    15.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.7
         upper limit
    		 74.2
    Notes
    [258] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 350 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9418 [259]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -2.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -78.5
         upper limit
    		 72.9
    Notes
    [259] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 250 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6452 [260]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -58.8
         upper limit
    		 94.7
    Notes
    [260] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 150 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2565 [261]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -51.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -140.2
         upper limit
    		 37.6
    Notes
    [261] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 100 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6605 [262]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -21.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -118.6
         upper limit
    		 75.4
    Notes
    [262] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    Placebo (Randomised Treatment Period) v FE 201836 50 µg (Randomised Treatment Period)
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9191 [263]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -62.6
         upper limit
    		 69.4
    Notes
    [263] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment

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    End point title
    		 Change From Baseline in Aggregated Mean Duration of FUSP During 12 Weeks of Treatment [264]
    End point description
    The FUSP is defined as the time in minutes from the time of going to bed to the time of first nocturnal void, or time of awakening if no void occurred. The visit-specific means were aggregated into a mean of current and preceding visits. Level estimated for baseline value of mean duration of FUSP (minutes) equal to 180 is presented in this endpoint. The 95% credibility interval (2.5 and 97.5 percentiles of the posterior distribution) instead of confidence interval is presented for this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, During 12 Weeks of Treatment
    Notes
    [264] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    60
    27
    24
    14
    13
    34
    87
    Units: minutes
        arithmetic mean (confidence interval 95%)
    154.98 (130.41 to 189.10)
    150.23 (130.20 to 181.15)
    145.95 (128.21 to 170.90)
    140.74 (120.51 to 160.16)
    139.19 (117.86 to 157.42)
    138.13 (115.62 to 157.24)
    137.45 (114.12 to 157.30)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    17.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.19
         upper limit
    		 62.09
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    12.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.73
         upper limit
    		 55.89
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    8.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 47.28
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    3.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.01
         upper limit
    		 28.07
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    1.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 17.9
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Statistical analysis description
    Based on a Bayesian analysis of a sigmoidal dose-response relationship.
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean Difference
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 7.55

    Secondary: Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1

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    End point title
    		 Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 1 [265]
    End point description
    The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed. Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented. Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    Notes
    [265] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    53
    24
    24
    14
    11
    32
    78
    Units: mL/min
        arithmetic mean (confidence interval 95%)
    -0.575 (-0.687 to -0.463)
    -0.635 (-0.801 to -0.468)
    -0.610 (-0.779 to -0.440)
    -0.459 (-0.678 to -0.239)
    -0.523 (-0.766 to -0.280)
    -0.328 (-0.474 to -0.182)
    -0.402 (-0.494 to -0.310)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0196 [266]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.173
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.318
         upper limit
    		 -0.028
    Notes
    [266] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0167 [267]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.233
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.423
         upper limit
    		 -0.043
    Notes
    [267] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0352 [268]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.208
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.401
         upper limit
    		 -0.015
    Notes
    [268] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6402 [269]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.057
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.295
         upper limit
    		 0.182
    Notes
    [269] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3602 [270]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.121
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.381
         upper limit
    		 0.139
    Notes
    [270] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4018 [271]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.074
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.099
         upper limit
    		 0.247
    Notes
    [271] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12

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    End point title
    		 Change From Baseline in Nocturnal Diuresis Rate Profiles at Week 12 [272]
    End point description
    The nocturnal diuresis rate (mL/min) is calculated as the mean of the nocturnal diuresis for each of the three nights, with the single-night nocturnal diuresis calculated as the ratio of NUV to total time in bed. Change from baseline in visit-specific mean nocturnal diuresis (mL/min) is presented. Level estimated for baseline value of mean nocturnal diuresis (mL/min) equal to 1.3 is presented in this endpoint. The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [272] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    35
    18
    18
    14
    11
    29
    68
    Units: mL/min
        arithmetic mean (confidence interval 95%)
    -0.648 (-0.789 to -0.508)
    -0.606 (-0.805 to -0.408)
    -0.735 (-0.937 to -0.533)
    -0.458 (-0.693 to -0.223)
    -0.685 (-0.945 to -0.425)
    -0.651 (-0.812 to -0.490)
    -0.515 (-0.619 to -0.412)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1354 [273]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.133
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.308
         upper limit
    		 0.042
    Notes
    [273] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4238 [274]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.091
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.315
         upper limit
    		 0.133
    Notes
    [274] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0574 [275]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.446
         upper limit
    		 0.007
    Notes
    [275] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6579 [276]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    0.058
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.199
         upper limit
    		 0.315
    Notes
    [276] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2337 [277]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.45
         upper limit
    		 0.11
    Notes
    [277] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1639 [278]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -0.136
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.328
         upper limit
    		 0.056
    Notes
    [278] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Mean NUV in Week 1

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    End point title
    		 Change From Baseline in Mean NUV in Week 1 [279]
    End point description
    The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning. The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL). The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 1
    Notes
    [279] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    53
    24
    24
    14
    11
    32
    78
    Units: mL
        arithmetic mean (confidence interval 95%)
    -328.8 (-395.3 to -262.3)
    -371.8 (-470.4 to -273.3)
    -352.4 (-452.8 to -252.1)
    -265.5 (-395.5 to -135.6)
    -312.6 (-455.9 to -169.3)
    -218.2 (-304.9 to -131.6)
    -241.6 (-296.3 to -186.9)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.047
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -87.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -173.2
         upper limit
    		 -1.2
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0237
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -130.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -242.9
         upper limit
    		 -17.6
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0569
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -110.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -224.9
         upper limit
    		 3.3
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7383
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -23.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -164.8
         upper limit
    		 117
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3626
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -224.3
         upper limit
    		 82.3
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6524
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    23.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -78.9
         upper limit
    		 125.7

    Secondary: Change From Baseline in Mean NUV at Week 12

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    End point title
    		 Change From Baseline in Mean NUV at Week 12 [280]
    End point description
    The NUV is defined as the total urine volume from 5 minutes after bedtime with the intention to sleep including the first void within 30 minutes of rising in the morning. The NUV at each visit was calculated as the average over the 3 consecutive 24-hour periods just prior to the respective visit. Adjusted visit-specific mean changes from baseline in NUV are estimated using a baseline value of 750 (mL). The analysis population included ITT-RT which comprised of all the subjects randomised at Visit 4.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [280] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Treatment comparison refers to the pair-wise comparison between active treatment (the different doses of FE 201836) and placebo. Desmopressin was included as a benchmark treatment only. None of the secondary analyses included data from subjects treated with desmopressin.
    End point values
    		 FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period)
    Number of subjects analysed
    35
    18
    18
    14
    11
    29
    68
    Units: mL
        arithmetic mean (confidence interval 95%)
    -367.3 (-447.1 to -287.5)
    -392.4 (-505.2 to -279.5)
    -411.3 (-526.0 to -296.7)
    -284.2 (-418.4 to -149.9)
    -393.5 (-541.9 to -245.1)
    -403.2 (-495.5 to -310.9)
    -317.8 (-377.1 to -258.5)
    Statistical analysis title
    		 FE 201836 500 ug, Placebo
    Comparison groups
    FE 201836 500 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3273 [281]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -49.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -148.9
         upper limit
    		 49.9
    Notes
    [281] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 350 ug, Placebo
    Comparison groups
    FE 201836 350 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.25 [282]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -74.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -202
         upper limit
    		 52.9
    Notes
    [282] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 250 ug, Placebo
    Comparison groups
    FE 201836 250 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1537 [283]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -93.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -222.3
         upper limit
    		 35.2
    Notes
    [283] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 150 ug, Placebo
    Comparison groups
    FE 201836 150 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6515 [284]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    33.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -113.1
         upper limit
    		 180.3
    Notes
    [284] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 100 ug, Placebo
    Comparison groups
    FE 201836 100 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3506 [285]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -75.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -235.3
         upper limit
    		 83.9
    Notes
    [285] - Threshold for significance at 0.05 level.
    Statistical analysis title
    		 FE 201836 50 ug, Placebo
    Comparison groups
    FE 201836 50 µg (Randomised Treatment Period) v Placebo (Randomised Treatment Period)
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1255 [286]
    Method
    		 MMRM
    Parameter type
    		 Mean Difference
    Point estimate
    -85.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -194.8
         upper limit
    		 24.1
    Notes
    [286] - Threshold for significance at 0.05 level.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AE) occurring in time interval from V2 (active run-in) to V4 (randomisation), including AEs with missing start date were considered ‘enrichment-treatment emergent’. AEs occurring from V4 to end-of-trial were considered ‘treatment-emergent'
    Adverse event reporting additional description
    The Safety Analysis Set for enrichment period comprised subjects who received investigational medicinal product (IMP) at V2 and did not return all IMP unused at/before V4. Safety Analysis Set for randomised treatment period comprised subjects who received IMP at V4 and did not return all IMP unused, and who had at least 1 safety assessment after V4
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    FE 201836 500 µg (Enrichment Period)
    Reporting group description
    		 FE 201836 500 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 500 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 500 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 350 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 350 µg oral solution and placebo ODT

    Reporting group title
    FE 201836 250 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 250 μg oral solution and placebo ODT

    Reporting group title
    FE 201836 150 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 150 μg oral solution and placebo ODT

    Reporting group title
    FE 201836 100 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 100 μg oral solution and placebo ODT

    Reporting group title
    FE 201836 50 µg (Randomised Treatment Period)
    Reporting group description
    		 FE 201836 50 μg oral solution and placebo ODT

    Reporting group title
    Placebo (Randomised Treatment Period)
    Reporting group description
    		 Placebo oral solution and placebo ODT

    Reporting group title
    Desmopressin 25 µg (Randomised Treatment Period)
    Reporting group description
    		 Desmopressin 25 µg ODT and placebo oral solution

    Reporting group title
    Desmopressin 50 µg (Randomised Treatment Period)
    Reporting group description
    		 Desmopressin 50 µg ODT and placebo oral solution

    Serious adverse events
    		 FE 201836 500 µg (Enrichment Period) FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period) Desmopressin 25 µg (Randomised Treatment Period) Desmopressin 50 µg (Randomised Treatment Period)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 531 (0.38%)
    1 / 60 (1.67%)
    2 / 27 (7.41%)
    1 / 24 (4.17%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 34 (0.00%)
    2 / 87 (2.30%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    1 / 27 (3.70%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    1 / 27 (3.70%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Facial bones fracture
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    1 / 24 (4.17%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    1 / 24 (4.17%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    1 / 24 (4.17%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Serum sickness-like reaction
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 60 (1.67%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    1 / 27 (3.70%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    1 / 27 (3.70%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    2 / 531 (0.38%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 FE 201836 500 µg (Enrichment Period) FE 201836 500 µg (Randomised Treatment Period) FE 201836 350 µg (Randomised Treatment Period) FE 201836 250 µg (Randomised Treatment Period) FE 201836 150 µg (Randomised Treatment Period) FE 201836 100 µg (Randomised Treatment Period) FE 201836 50 µg (Randomised Treatment Period) Placebo (Randomised Treatment Period) Desmopressin 25 µg (Randomised Treatment Period) Desmopressin 50 µg (Randomised Treatment Period)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 531 (0.00%)
    16 / 60 (26.67%)
    3 / 27 (11.11%)
    3 / 24 (12.50%)
    8 / 14 (57.14%)
    5 / 13 (38.46%)
    7 / 34 (20.59%)
    16 / 87 (18.39%)
    8 / 26 (30.77%)
    9 / 17 (52.94%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 60 (1.67%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    1 / 34 (2.94%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    1
    2
    0
    0
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    2 / 87 (2.30%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    2
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    1 / 26 (3.85%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    1
    Investigations
    Weight increased
         subjects affected / exposed
    0 / 531 (0.00%)
    3 / 60 (5.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    1 / 26 (3.85%)
    0 / 17 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    1
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 531 (0.00%)
    2 / 60 (3.33%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    2 / 14 (14.29%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    2
    0
    0
    0
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    1 / 26 (3.85%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    1
    Blood sodium decreased
         subjects affected / exposed
    0 / 531 (0.00%)
    2 / 60 (3.33%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    2
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    3 / 26 (11.54%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    2 / 14 (14.29%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    2 / 14 (14.29%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Blood alkaline phosphatase
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    1 / 24 (4.17%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 34 (2.94%)
    3 / 87 (3.45%)
    0 / 26 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    4
    0
    6
    Hand fracture
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Laceration
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Road traffic accident
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 531 (0.00%)
    3 / 60 (5.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 34 (2.94%)
    2 / 87 (2.30%)
    1 / 26 (3.85%)
    0 / 17 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    1
    2
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 60 (1.67%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    1 / 34 (2.94%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    1
    1
    1
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 34 (2.94%)
    0 / 87 (0.00%)
    1 / 26 (3.85%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    3
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    0 / 531 (0.00%)
    3 / 60 (5.00%)
    1 / 27 (3.70%)
    2 / 24 (8.33%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 34 (2.94%)
    3 / 87 (3.45%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    3
    1
    2
    0
    0
    1
    4
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 531 (0.00%)
    2 / 60 (3.33%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    1 / 34 (2.94%)
    1 / 87 (1.15%)
    1 / 26 (3.85%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    1
    1
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    2 / 14 (14.29%)
    0 / 13 (0.00%)
    1 / 34 (2.94%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    1
    0
    1
    Constipation
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    Renal impairment
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    0 / 531 (0.00%)
    2 / 60 (3.33%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    1
    0
    0
    0
    0
    Joint swelling
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    1 / 24 (4.17%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 531 (0.00%)
    3 / 60 (5.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    1 / 26 (3.85%)
    0 / 17 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    Cellulitis
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 531 (0.00%)
    3 / 60 (5.00%)
    2 / 27 (7.41%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 34 (0.00%)
    0 / 87 (0.00%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    5
    2
    0
    0
    1
    0
    0
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    0 / 531 (0.00%)
    0 / 60 (0.00%)
    0 / 27 (0.00%)
    0 / 24 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 34 (0.00%)
    1 / 87 (1.15%)
    0 / 26 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Dec 2017
    The reason for this protocol amendment was to implement changes to the clinical trial protocol in agreement with Competent Authorities and Independent Ethics Committees in countries where the trial was conducted, following review of Clinical Trial Protocol version 2.0, dated 04 January 2017.
    05 Jul 2018
    The reason for this protocol amendment was to update according to recent guidelines and research within lower urinary tract symptoms (LUTS) and to enhance subject recruitment.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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