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    Clinical Trial Results:
    A DOUBLE-BLIND, RANDOMISED, PLACEBO CONTROLLED, TWO PERIOD CROSS-OVER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ORVEPITANT IN CHRONIC COUGH IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS

    Summary
    EudraCT number
    		 2021-006278-22
    Trial protocol
    		 NL  
    Global end of trial date
    19 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Aug 2025
    First version publication date
    07 Aug 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ORV-PF-01
    Additional study identifiers
    ISRCTN number
    		 ISRCTN12372820
    US NCT number
    		 NCT05185089
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    NeRRe Therapeutics Ltd
    Sponsor organisation address
    SBC, Incubator Building, Gunnels Wood Road, Stevenage, United Kingdom, SG1 2FX
    Public contact
    Susan Seymore, NeRRe Therapeutics Ltd, info@nerretherapeutics.com
    Scientific contact
    Dr. Steve Pawsey, NeRRe Therapeutics Ltd, info@nerretherapeutics.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
    16 Jul 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Jun 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Main objective of the trial: • To evaluate the effect of orvepitant once daily on cough severity, as perceived by patients, with IPF • To evaluate the safety of orvepitant once daily in patients with IPF
    Protection of trial subjects
    Trial selection criteria excluded subjects that could not participate safely in the study and medications with potential interactions with the study drug were restricted or prohibited. Subject safety was closely monitored by regular safety assessments (vital signs, spirometry, physical exams, ECGs and blood & urine tests) and AEs were continuously monitored. The safety of the study drug also monitored by an independent Data Safety Monitoring Board.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Aug 2022
    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
    Netherlands: 5
    Country: Number of subjects enrolled
    United Kingdom: 54
    Country: Number of subjects enrolled
    United States: 21
    Worldwide total number of subjects
    80
    EEA total number of subjects
    5
    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)
    12
    From 65 to 84 years
    66
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted between 01 August 2022 and 19 June 2024 at 37 sites in the USA, UK and NL (of which 32 sites screened at least one subject and 28 randomised at least one subject. A total of 123 subjects were screened, of whom 80 (65.0%) completed Screening and were randomised.

    Pre-assignment
    Screening details
    		 Subjects who satisfied all criteria and in whom no clinically relevant laboratory abnormalities were anticipated, were provided with an eDiary and trained on its use. The diary was then completed throughout the screening period before the subject returned for the baseline visit.

    Period 1
    Period 1 title
    Treatment Period A+B (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor
    Blinding implementation details
    The study was conducted in a double-blind manner, with the subjects, Investigators and Sponsor’s study management team (and including CROs) all blinded to the treatment allocated. Both orvepitant (10 and 30 mg) and placebo were presented as white tablets, identical in size and shape.

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Placebo (10 mg Cohort)
    Arm description
    		 Placebo once-daily for 4 weeks in either Period A or Period B (subjects assigned to orvepitant 10mg cohort).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One placebo tablet (oral) once-daily for 4 weeks

    Arm title
    		 Orvepitant 10mg
    Arm description
    		 Orvepitant 10 mg once-daily for 4 weeks in either Period A or Period B.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Orvepitant 10 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One 10 mg orvepitant tablet (oral) once-daily for 4 weeks

    Arm title
    		 Placebo (30 mg Cohort)
    Arm description
    		 Placebo once-daily for 4 weeks in either Period A or Period B (subjects assigned to orvepitant 30mg cohort).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo 30 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One placebo tablet (oral) once-daily for 4 weeks

    Arm title
    		 Orvepitant 30mg
    Arm description
    		 Orvepitant 30 mg once-daily for 4 weeks in either Period A or Period B.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Orvepitant 30mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One 30 mg orvepitant tablet (oral) once-daily for 4 weeks

    Number of subjects in period 1
    		Placebo (10 mg Cohort) Orvepitant 10mg Placebo (30 mg Cohort) Orvepitant 30mg
    Started
    40
    40
    39
    40
    Completed
    39
    39
    39
    39
    Not completed
    1
    1
    0
    1
         Adverse event, serious fatal
    1
    -
    -
    -
         Adverse event, non-fatal
    -
    1
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment Period A+B
    Reporting group description
    		 -

    Reporting group values
    		 Treatment Period A+B Total
    Number of subjects
    		 80 80
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 12 12
        From 65-84 years
    		 66 66
        85 years and over
    		 2 2
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 71.9 ( 7.17 ) -
    Gender categorical
    Units: Subjects
        Female
    		 21 21
        Male
    		 59 59

    End points

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    End points reporting groups
    Reporting group title
    Placebo (10 mg Cohort)
    Reporting group description
    		 Placebo once-daily for 4 weeks in either Period A or Period B (subjects assigned to orvepitant 10mg cohort).

    Reporting group title
    Orvepitant 10mg
    Reporting group description
    		 Orvepitant 10 mg once-daily for 4 weeks in either Period A or Period B.

    Reporting group title
    Placebo (30 mg Cohort)
    Reporting group description
    		 Placebo once-daily for 4 weeks in either Period A or Period B (subjects assigned to orvepitant 30mg cohort).

    Reporting group title
    Orvepitant 30mg
    Reporting group description
    		 Orvepitant 30 mg once-daily for 4 weeks in either Period A or Period B.

    Primary: Mean Change from Baseline to Week 4 in Weekly Average of the Daily IPF Coughing Severity Scale

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    End point title
    		 Mean Change from Baseline to Week 4 in Weekly Average of the Daily IPF Coughing Severity Scale
    End point description
    Note, there was a significant (p=0.048) treatment by period interaction for the 30 mg cohort.
    End point type
    Primary
    End point timeframe
    Baseline to Week 4
    End point values
    		 Placebo (10 mg Cohort) Orvepitant 10mg Placebo (30 mg Cohort) Orvepitant 30mg
    Number of subjects analysed
    39
    39
    39
    39
    Units: Units on a scale
        least squares mean (standard error)
    -0.6 ( 0.219 )
    -0.66 ( 0.219 )
    -0.26 ( 0.207 )
    -0.84 ( 0.207 )
    Statistical analysis title
    		 Difference versus placebo at Week 4 (10mg)
    Comparison groups
    Orvepitant 10mg v Placebo (10 mg Cohort)
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.989
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.62
         upper limit
    		 0.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.305
    Statistical analysis title
    		 Difference versus placebo at Week 4 (30mg)
    Comparison groups
    Orvepitant 30mg v Placebo (30 mg Cohort)
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.054
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.16
         upper limit
    		 0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.293

    Secondary: Mean Change from Baseline to Week 4 in Weekly Average of the Urge to Cough Scale Score

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    End point title
    		 Mean Change from Baseline to Week 4 in Weekly Average of the Urge to Cough Scale Score
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Week 4
    End point values
    		 Placebo (10 mg Cohort) Orvepitant 10mg Placebo (30 mg Cohort) Orvepitant 30mg
    Number of subjects analysed
    39
    39
    39
    39
    Units: Units on a scale
        least squares mean (standard error)
    -0.47 ( 0.213 )
    -0.61 ( 0.212 )
    -0.30 ( 0.191 )
    -0.76 ( 0.191 )
    Statistical analysis title
    		 Difference versus placebo at Week 4 (10mg)
    Comparison groups
    Placebo (10 mg Cohort) v Orvepitant 10mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.639
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.73
         upper limit
    		 0.45
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.291
    Statistical analysis title
    		 Difference versus placebo at Week 4 (30mg)
    Comparison groups
    Placebo (30 mg Cohort) v Orvepitant 30mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.092
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.271

    Secondary: Mean Change from Baseline to Week 4 in Weekly Average of the Cough Frequency Scale Score

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    End point title
    		 Mean Change from Baseline to Week 4 in Weekly Average of the Cough Frequency Scale Score
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Week 4
    End point values
    		 Placebo (10 mg Cohort) Orvepitant 10mg Placebo (30 mg Cohort) Orvepitant 30mg
    Number of subjects analysed
    39
    39
    39
    39
    Units: units on a scale
        least squares mean (standard error)
    -0.19 ( 0.083 )
    -0.15 ( 0.083 )
    -0.05 ( 0.067 )
    -0.29 ( 0.067 )
    Statistical analysis title
    		 Difference versus placebo at Week 4 (10mg)
    Comparison groups
    Placebo (10 mg Cohort) v Orvepitant 10mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.65
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.17
         upper limit
    		 0.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.104
    Statistical analysis title
    		 Difference versus placebo at Week 4 (30mg)
    Comparison groups
    Placebo (30 mg Cohort) v Orvepitant 30mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.01
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.41
         upper limit
    		 -0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.085

    Secondary: Mean Change from Baseline in Week 4 of the Dyspnoea Scale Score

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    End point title
    		 Mean Change from Baseline in Week 4 of the Dyspnoea Scale Score
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Week 4
    End point values
    		 Placebo (10 mg Cohort) Orvepitant 10mg Placebo (30 mg Cohort) Orvepitant 30mg
    Number of subjects analysed
    39
    39
    39
    39
    Units: Units on a scale
        least squares mean (standard error)
    -0.26 ( 0.172 )
    -0.21 ( 0.172 )
    0.01 ( 0.148 )
    -0.44 ( 0.148 )
    Statistical analysis title
    		 Difference versus placebo at Week 4 (10mg)
    Comparison groups
    Placebo (10 mg Cohort) v Orvepitant 10mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.856
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.44
         upper limit
    		 0.53
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.24
    Statistical analysis title
    		 Difference versus placebo at Week 4 (30mg)
    Comparison groups
    Placebo (30 mg Cohort) v Orvepitant 30mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.036
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.87
         upper limit
    		 -0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.21

    Secondary: Mean Change from Baseline to Week 4 in LCQ Total Scores

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    End point title
    		 Mean Change from Baseline to Week 4 in LCQ Total Scores
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Week 4
    End point values
    		 Placebo (10 mg Cohort) Orvepitant 10mg Placebo (30 mg Cohort) Orvepitant 30mg
    Number of subjects analysed
    39
    39
    39
    39
    Units: Units on a scale
        least squares mean (standard error)
    1.06 ( 0.326 )
    1.25 ( 0.326 )
    0.24 ( 0.387 )
    1.48 ( 0.388 )
    Statistical analysis title
    		 Difference versus placebo at Week 4 (10mg)
    Comparison groups
    Placebo (10 mg Cohort) v Orvepitant 10mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.678
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.73
         upper limit
    		 1.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.462
    Statistical analysis title
    		 Difference versus placebo at Week 4 (30mg)
    Comparison groups
    Placebo (30 mg Cohort) v Orvepitant 30mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.025
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.16
         upper limit
    		 2.31
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.525

    Secondary: Mean Change from Baseline to Week 4 in 24-hour Cough Frequency (Number of Coughs per Hour)

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    End point title
    		 Mean Change from Baseline to Week 4 in 24-hour Cough Frequency (Number of Coughs per Hour)
    End point description
    Mean change from Baseline to Week 4 in 24-hour cough frequency
    End point type
    Secondary
    End point timeframe
    Baseline to Week 4 in 24-hour cough frequency
    End point values
    		 Placebo (10 mg Cohort) Orvepitant 10mg Placebo (30 mg Cohort) Orvepitant 30mg
    Number of subjects analysed
    32
    31
    32
    32
    Units: Coughs per hour (ratio vs baseline)
        least squares mean (standard error)
    0.93 ( 1.114 )
    1.00 ( 1.115 )
    0.84 ( 1.113 )
    0.87 ( 1.112 )
    Statistical analysis title
    		 Difference versus placebo at Week 4 (10mg)
    Comparison groups
    Placebo (10 mg Cohort) v Orvepitant 10mg
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.438
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.33
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.105
    Statistical analysis title
    		 Difference versus placebo at Week 4 (30mg)
    Comparison groups
    Placebo (30 mg Cohort) v Orvepitant 30mg
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.761
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.31
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.222

    Secondary: Mean Change from Baseline to Week 4 in 24-hour Cough Frequency (Number of Bouts per Hour)

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    End point title
    		 Mean Change from Baseline to Week 4 in 24-hour Cough Frequency (Number of Bouts per Hour)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Week 4
    End point values
    		 Placebo (10 mg Cohort) Orvepitant 10mg Placebo (30 mg Cohort) Orvepitant 30mg
    Number of subjects analysed
    32
    31
    32
    32
    Units: Bouts per hour (ratio vs baseline)
        least squares mean (standard error)
    0.91 ( 1.089 )
    1.00 ( 1.090 )
    0.82 ( 1.087 )
    0.88 ( 1.087 )
    Statistical analysis title
    		 Difference versus placebo at Week 4 (10mg)
    Comparison groups
    Placebo (10 mg Cohort) v Orvepitant 10mg
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.287
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 1.29
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.084
    Statistical analysis title
    		 Difference versus placebo at Week 4 (30mg)
    Comparison groups
    Placebo (30 mg Cohort) v Orvepitant 30mg
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.42
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.29
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.092

    Secondary: Mean Change from Baseline to Week 4 in 24-hour Cough Frequency (Number of Coughs per Bout)

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    End point title
    		 Mean Change from Baseline to Week 4 in 24-hour Cough Frequency (Number of Coughs per Bout)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Week 4
    End point values
    		 Placebo (10 mg Cohort) Orvepitant 10mg Placebo (30 mg Cohort) Orvepitant 30mg
    Number of subjects analysed
    30
    30
    32
    32
    Units: Coughs per bout (ratio vs baseline)
        least squares mean (standard error)
    0.91 ( 1.027 )
    0.92 ( 1.027 )
    0.98 ( 1.028 )
    0.89 ( 1.028 )
    Statistical analysis title
    		 Difference versus placebo at Week 4 (10mg)
    Comparison groups
    Placebo (10 mg Cohort) v Orvepitant 10mg
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.765
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.022
    Statistical analysis title
    		 Difference versus placebo at Week 4 (30mg)
    Comparison groups
    Placebo (30 mg Cohort) v Orvepitant 30mg
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 0.97
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.033

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Throughout the study
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Placebo (10 mg Cohort)
    Reporting group description
    		 AEs started during placebo treatment in a subject in the Orvepitant 10 mg cohort.

    Reporting group title
    Orvepitant 10 mg
    Reporting group description
    		 AEs started during treatment with orvepitant 10 mg.

    Reporting group title
    Placebo (30 mg Cohort)
    Reporting group description
    		 AEs started during placebo treatment in a subject in the Orvepitant 30 mg cohort.

    Reporting group title
    Orvepitant 30 mg
    Reporting group description
    		 AEs started during treatment with orvepitant 30 mg

    Serious adverse events
    		 Placebo (10 mg Cohort) Orvepitant 10 mg Placebo (30 mg Cohort) Orvepitant 30 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 40 (2.50%)
    3 / 38 (7.89%)
    1 / 39 (2.56%)
         number of deaths (all causes)
    0
    1
    0
    0
         number of deaths resulting from adverse events
    0
    1
    0
    0
    Investigations
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Obstructive pancreatitis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 40 (2.50%)
    0 / 38 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo (10 mg Cohort) Orvepitant 10 mg Placebo (30 mg Cohort) Orvepitant 30 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 40 (45.00%)
    30 / 40 (75.00%)
    17 / 38 (44.74%)
    20 / 39 (51.28%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    2 / 38 (5.26%)
    2 / 39 (5.13%)
         occurrences all number
    1
    2
    2
    2
    Headache
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    1 / 39 (2.56%)
         occurrences all number
    3
    1
    1
    1
    Lethargy
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 40 (7.50%)
    3 / 40 (7.50%)
    1 / 38 (2.63%)
    2 / 39 (5.13%)
         occurrences all number
    3
    3
    1
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 40 (5.00%)
    4 / 40 (10.00%)
    1 / 38 (2.63%)
    2 / 39 (5.13%)
         occurrences all number
    2
    4
    1
    2
    Abdominal pain upper
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    1 / 38 (2.63%)
    3 / 39 (7.69%)
         occurrences all number
    1
    2
    1
    3
    Dyspnoea
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    3 / 39 (7.69%)
         occurrences all number
    2
    0
    2
    3
    Sputum increased
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    1 / 38 (2.63%)
    2 / 39 (5.13%)
         occurrences all number
    0
    0
    1
    2
    Haemoptysis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 40 (0.00%)
    2 / 38 (5.26%)
    0 / 39 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 40 (0.00%)
    0 / 38 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 40 (5.00%)
    0 / 38 (0.00%)
    1 / 39 (2.56%)
         occurrences all number
    1
    2
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 40 (7.50%)
    0 / 38 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 40 (7.50%)
    4 / 38 (10.53%)
    0 / 39 (0.00%)
         occurrences all number
    1
    3
    4
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 40 (0.00%)
    3 / 40 (7.50%)
    2 / 38 (5.26%)
    2 / 39 (5.13%)
         occurrences all number
    0
    3
    3
    2
    COVID-19
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 40 (2.50%)
    1 / 38 (2.63%)
    2 / 39 (5.13%)
         occurrences all number
    1
    1
    1
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 40 (0.00%)
    3 / 40 (7.50%)
    0 / 38 (0.00%)
    0 / 39 (0.00%)
         occurrences all number
    0
    3
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Feb 2022
    Protocol version 2.0 (Amendment 1) •Revisions to patient reported outcomes made in response to FDA feedback on protocol. •This was the first version of the protocol implemented in the study (version 1.0 never implemented). •A country specific version was implemented in the Netherlands (Version 2.1 NL 05 Jul 2022) to incorporate additional NL-specific changes, requested by the ethics committee, namely to reflect the 2013 version of the Declaration of Helsinki, add a section addressing post-trial access to IMP, and clarify that subjects would be randomised to cohort and treatment order using a single, blocked randomisation list.
    05 Apr 2023
    Protocol version 3.0 (Amendment 2) was a non-substantial amendment: • Small changes were made to several of the selection criteria but without meaningfully changing the overall nature of the recruited study population. •Clarified the use of concomitant respiratory medications. •Clarified the requirements with respect to PFTs. •Removed the limitation on reducing the sample size if the sample size re-estimate showed the study was likely to be over-powered. •Clarified the concomitant use of CYP3A4 inhibitors and inducers and P-glycoprotein inhibitors. Country-specific versions were implemented in the UK & NL: •The UK version (Version 3.1 UK 05April2023) incorporated allowance for the collection of additional blood samples for analysis of more biomarkers. •The NL version (Version 3.1 NL 05April2023) included the previous NL-specific changes.
    16 May 2024
    Protocol version 4.0 (Amendment 3) was a non-substantial amendment implemented in US only to correct some typographical errors in the sample size section and fully align statistical text in the protocol with the equivalent text in the SAP, at the request of the FDA.

    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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