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    Clinical Trial Results:
    A prospective, double-blind, randomised, placebo-controlled trial on the efficacy and safety of Neiromidin 20 mg tablets in the treatment of patients with lumbosacral radiculopathy

    Summary
    EudraCT number
    		 2019-002632-90
    Trial protocol
    		 PL   CZ   LV   BG  
    Global end of trial date
    10 Mar 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Jun 2026
    First version publication date
    07 Jun 2026
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    OF_NEIR_CT1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    „Olainfarm“ AS
    Sponsor organisation address
    5 Rupnicu Street, Olaine, Latvia, LV-2114
    Public contact
    Olpha, Olpha, +371 67013708, olpha@olpha.eu
    Scientific contact
    Olpha, Olpha, +371 67013708, olpha@olpha.eu
    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
    29 May 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 Mar 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Mar 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the superiority of Neiromidin 20 mg tablets relative to placebo for the change in disability score (as assessed using Oswestry Disability Index [ODI]) from baseline to the end of 6-week treatment in patients with lumbosacral radiculopathy
    Protection of trial subjects
    Specific measures - not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Jun 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 204
    Country: Number of subjects enrolled
    Bulgaria: 50
    Country: Number of subjects enrolled
    Czechia: 147
    Country: Number of subjects enrolled
    Latvia: 23
    Worldwide total number of subjects
    424
    EEA total number of subjects
    424
    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)
    418
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 All study subjects were recruited at the outpatient neurology clinics between July 2021 and December 2023.

    Pre-assignment
    Screening details
    		 The screening procedures were performed within a 1-7 day period before recruitment (randomization). All the results of screening procedures were required to be available before recruitment.

    Pre-assignment period milestones
    Number of subjects started
    		 470 [1]
    Intermediate milestone: Number of subjects
    Enrolled: 424
    Intermediate milestone: Number of subjects
    Included in Full analysis set: 403
    Number of subjects completed
    		 403

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Consent withdrawn by subject: 26
    Reason: Number of subjects
    		 Lost of follow-up: 6
    Reason: Number of subjects
    		 Adverse event, non-fatal: 6
    Reason: Number of subjects
    		 Adverse event, serious fatal: 1
    Reason: Number of subjects
    		 Screening failure: 26
    Reason: Number of subjects
    		 Unspecified: 2
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number of subjects screened for inclusion is provided for a pre-assignment period; the number of enrolled subjects is different.
    Period 1
    Period 1 title
    Treatment (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    The study was double-blind. Patients were randomised to receive Neiromidin 20 mg tablets or matching placebo in a 1:1 allocation ratio using an adaptive randomisation algorithm with balancing for study/country/location factors. Subjects were centrally randomized using an Interactive Web Response Service. The specifications for generation of the randomization were prepared by an independent statistician.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Active
    Arm description
    		 Full analysis set
    Arm type
    		 Experimental

    Investigational medicinal product name
    Neiromidin 20 mg tablets
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 (one) Neiromidin 20 mg tablet three times a day for 6 weeks (42 days).

    Arm title
    		 Placebo
    Arm description
    		 Full analysis set
    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
    Placebo (three times a day) tablets for 6 weeks (42 days).

    Number of subjects in period 1 [2]
    		Active Placebo
    Started
    206
    197
    Completed
    206
    197
    Notes
    [2] - 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: The worldwide number of enrolled subjects refers to the ITT population. The primary analysis of all efficacy variables was performed and reported on the Full analysis set, thus the FUL is used as a baseline.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Active
    Reporting group description
    		 Full analysis set

    Reporting group title
    Placebo
    Reporting group description
    		 Full analysis set

    Reporting group values
    		 Active Placebo Total
    Number of subjects
    		 206 197 403
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 203 194 397
        From 65-84 years
    		 3 3 6
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 49.8 ( 9.3 ) 50.7 ( 9.5 ) -
    Gender categorical
    Units: Subjects
        Female
    		 116 122 238
        Male
    		 90 75 165
    Race
    Units: Subjects
        White
    		 206 197 403
    Body mass index
    Units: kg/m2
        arithmetic mean (standard deviation)
    		 28.55 ( 4.69 ) 28.12 ( 4.87 ) -
    Subject analysis sets

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety analysis set

    Subject analysis sets values
    		 Safety analysis set
    Number of subjects
    423
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    417
        From 65-84 years
    6
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    50.1 ( 9.5 )
    Gender categorical
    Units: Subjects
        Female
    245
        Male
    178
    Race
    Units: Subjects
        White
    423
    Body mass index
    Units: kg/m2
        arithmetic mean (standard deviation)
    28.33 ( 4.78 )

    End points

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    End points reporting groups
    Reporting group title
    Active
    Reporting group description
    		 Full analysis set

    Reporting group title
    Placebo
    Reporting group description
    		 Full analysis set

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety analysis set

    Primary: Oswestry Disability Index (ODI)

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    End point title
    		 Oswestry Disability Index (ODI)
    End point description
    Change in total ODI score from baseline (Day 0) to Week 6. Full analysis set.
    End point type
    Primary
    End point timeframe
    Baseline (Day 0) to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: Points
        least squares mean (confidence interval 95%)
    -12.20 (-13.96 to -10.45)
    -11.20 (-12.98 to -9.42)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 > 0.05
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.51
         upper limit
    		 1.5
    Notes
    [1] - Results display model-based mean difference between active and placebo with terms for treatment and ODI baseline value. Variable tested at a 5% significance level.

    Primary: Oswestry Disability Index (ODI) 2

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    End point title
    		 Oswestry Disability Index (ODI) 2
    End point description
    Change in total ODI score, excluding subjects with NSAID or rescue medication within 2 days prior to Day 42
    End point type
    Primary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: Points
        least squares mean (confidence interval 95%)
    -14.70 (-17.64 to -11.77)
    -11.04 (-13.85 to -8.23)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.0271
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.91
         upper limit
    		 -0.42
    Notes
    [2] - Results display model-based mean difference between active and placebo with terms for treatment, country and ODI baseline value. Variable tested at a 5% significance level.

    Secondary: Leg pain

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    End point title
    		 Leg pain
    End point description
    Change in leg pain intensity on the NRS
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: Points
        least squares mean (confidence interval 95%)
    -2.59 (-2.92 to -2.26)
    -2.72 (-3.05 to -2.38)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [3]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.35
         upper limit
    		 0.59
    Notes
    [3] - Variable tested at a 5% significance level

    Secondary: Low back pain

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    End point title
    		 Low back pain
    End point description
    Change in low back pain intensity on the NRS
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: Points
        least squares mean (confidence interval 95%)
    -1.47 (-1.73 to -1.21)
    -1.62 (-1.88 to -1.36)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.22
         upper limit
    		 0.52
    Notes
    [4] - Variable tested at a 5% significance level

    Secondary: Low back pain 2

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    End point title
    		 Low back pain 2
    End point description
    Change in low back pain intensity on the NRS
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: Points
        least squares mean (confidence interval 95%)
    -2.25 (-2.56 to -1.94)
    -2.40 (-2.72 to -2.09)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [5]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.29
         upper limit
    		 0.6
    Notes
    [5] - Variable tested at a 5% significance level

    Secondary: Sensory nerve conduction

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    End point title
    		 Sensory nerve conduction
    End point description
    Change in Sensory Conduction Velocity (SCV) in sensory nerve (sural), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: m/s
        least squares mean (confidence interval 95%)
    0.25 (-0.94 to 1.44)
    0.83 (-0.34 to 1.99)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [6]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.24
         upper limit
    		 1.09
    Notes
    [6] - Variable tested at a 5% significance level

    Secondary: Sensory nerve conduction 2

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    End point title
    		 Sensory nerve conduction 2
    End point description
    Change in Peak Latency in sensory nerve (sural), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: ms
        least squares mean (confidence interval 95%)
    -0.39 (-0.56 to -0.21)
    -0.35 (-0.52 to -0.18)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [7]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.28
         upper limit
    		 0.21
    Notes
    [7] - Variable tested at a 5% significance level

    Secondary: Sensory nerve conduction 3

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    End point title
    		 Sensory nerve conduction 3
    End point description
    Change in Distal Sensory Nerve Action Potential (SNAP) Amplitude in sensory nerve (sural), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: μV
        least squares mean (confidence interval 95%)
    0.41 (-1.70 to 2.53)
    1.05 (-1.02 to 3.13)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [8]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.61
         upper limit
    		 2.33
    Notes
    [8] - Variable tested at a 5% significance level

    Secondary: Motor nerve conduction

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    End point title
    		 Motor nerve conduction
    End point description
    Change in Motor Conduction Velocity (MCV) in motor nerve (peroneal), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: m/s
        least squares mean (confidence interval 95%)
    -0.30 (-1.19 to 0.59)
    0.01 (-0.87 to 0.89)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [9]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.56
         upper limit
    		 0.94
    Notes
    [9] - Variable tested at a 5% significance level

    Secondary: Motor nerve conduction 2

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    End point title
    		 Motor nerve conduction 2
    End point description
    Change in Motor Conduction Velocity (MCV) in motor nerve (tibial), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: ms
        least squares mean (confidence interval 95%)
    -0.64 (-1.45 to 0.17)
    -0.53 (-1.34 to 0.27)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [10]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.25
         upper limit
    		 1.04
    Notes
    [10] - Variable tested at a 5% significance level

    Secondary: Motor nerve conduction 3

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    End point title
    		 Motor nerve conduction 3
    End point description
    Change in Distal Motor Latency (DML) in motor nerve (peroneal), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: μV
        least squares mean (confidence interval 95%)
    0.06 (-0.26 to 0.38)
    -0.45 (-0.76 to -0.13)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [11]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.06
         upper limit
    		 0.96
    Notes
    [11] - Variable tested at a 5% significance level

    Secondary: Motor nerve conduction 4

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    End point title
    		 Motor nerve conduction 4
    End point description
    Change in Distal Motor Latency (DML) in motor nerve (tibial), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: ms
        least squares mean (confidence interval 95%)
    -0.12 (-0.60 to 0.36)
    -0.22 (-0.69 to 0.25)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [12]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.58
         upper limit
    		 0.77
    Notes
    [12] - Variable tested at a 5% significance level

    Secondary: Motor nerve conduction 5

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    End point title
    		 Motor nerve conduction 5
    End point description
    Change in Distal Compound Muscle Action Potential (CMAP) Amplitude in motor nerve (peroneal), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: mV
        least squares mean (confidence interval 95%)
    -0.04 (-0.61 to 0.53)
    -0.11 (-0.67 to 0.45)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [13]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.27
         upper limit
    		 0.87
    Notes
    [13] - Variable tested at a 5% significance level

    Secondary: Motor nerve conduction 6

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    End point title
    		 Motor nerve conduction 6
    End point description
    Change in Distal Compound Muscle Action Potential (CMAP) Amplitude in motor nerve (tibial), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: mV
        least squares mean (confidence interval 95%)
    0.11 (-0.77 to 0.99)
    -0.31 (-1.18 to 0.56)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [14]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.82
         upper limit
    		 1.66
    Notes
    [14] - Variable tested at a 5% significance level

    Secondary: Motor nerve conduction 7

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    End point title
    		 Motor nerve conduction 7
    End point description
    Change in late responses (minimal F-wave latency), in motor nerve (peroneal), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: m/s
        least squares mean (confidence interval 95%)
    0.44 (-0.34 to 1.21)
    -0.33 (-1.11 to 0.46)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [15]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.34
         upper limit
    		 1.87
    Notes
    [15] - Variable tested at a 5% significance level

    Secondary: Motor nerve conduction 8

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    End point title
    		 Motor nerve conduction 8
    End point description
    Change in late responses (minimal F-wave latency), in motor nerve (tibial), affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: m/s
        least squares mean (confidence interval 95%)
    0.31 (-0.26 to 0.87)
    -0.17 (-0.72 to 0.39)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [16]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.32
         upper limit
    		 1.26
    Notes
    [16] - Variable tested at a 5% significance level

    Secondary: Muscle strength (MRC scale)

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    End point title
    		 Muscle strength (MRC scale)
    End point description
    Change in muscle strength, plantar flexors - soleus, affected side
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 1.99

    Secondary: Muscle strength (MRC scale) 2

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    End point title
    		 Muscle strength (MRC scale) 2
    End point description
    Change in muscle strength, plantar flexors - soleus, affected side
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 1.88

    Secondary: Muscle strength (MRC scale) 3

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    End point title
    		 Muscle strength (MRC scale) 3
    End point description
    Change in muscle strength, plantar flexors - gastrocnemius, affected side
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Placebo v Active
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 1.62

    Secondary: Muscle strength (MRC scale) 4

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    End point title
    		 Muscle strength (MRC scale) 4
    End point description
    Change in muscle strength, plantar flexors - gastrocnemius, affected side
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 1.72

    Secondary: Muscle strength (MRC scale) 5

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    End point title
    		 Muscle strength (MRC scale) 5
    End point description
    Change in muscle strength, ankle dorsiflexor - tibialis anterior, affected side
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.74

    Secondary: Muscle strength (MRC scale) 6

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    End point title
    		 Muscle strength (MRC scale) 6
    End point description
    Change in muscle strength, ankle dorsiflexor - tibialis anterior, affected side
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 1.7

    Secondary: Muscle strength (MRC scale) 7

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    End point title
    		 Muscle strength (MRC scale) 7
    End point description
    Change in muscle strength, great toe extensor - hallucis longus, affected side
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Placebo v Active
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 1.34

    Secondary: Muscle strength (MRC scale) 8

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    End point title
    		 Muscle strength (MRC scale) 8
    End point description
    Change in muscle strength, great toe extensor - hallucis longus, affected side
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 1.22

    Secondary: Sensitivity

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    End point title
    		 Sensitivity
    End point description
    Change in sensitivity (Pinprick and light touch sensation) for S1 (lateral heel) dermatome
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.16
         upper limit
    		 1.31

    Secondary: Sensitivity 2

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    End point title
    		 Sensitivity 2
    End point description
    Change in sensitivity (Pinprick and light touch sensation) for S1 (lateral heel) dermatome
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 4.81

    Secondary: Sensitivity 3

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    End point title
    		 Sensitivity 3
    End point description
    Change in sensitivity (Pinprick and light touch sensation) for L5 (dorsum of the foot at the third metatarsal phalangeal joint) dermatome
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 1.79

    Secondary: Sensitivity 4

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    End point title
    		 Sensitivity 4
    End point description
    Change in sensitivity (Pinprick and light touch sensation) for L5 (dorsum of the foot at the third metatarsal phalangeal joint) dermatome
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.77

    Secondary: Reflexes

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    End point title
    		 Reflexes
    End point description
    Change in Achilles reflexes, affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.65

    Secondary: Reflexes 2

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    End point title
    		 Reflexes 2
    End point description
    Change in Achilles reflexes, affected leg
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GEE
    Statistical analysis description
    Results display comparison between active and placebo and are based on a generalised estimating equation (GEE) for a repeated proportional odds model including treatment, time and treatment*time interaction and muscle strength at baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.73

    Secondary: Patient Global Impression of Change

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    End point title
    		 Patient Global Impression of Change
    End point description
    Statistical analysis of PGIC response
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GLMM
    Statistical analysis description
    Results display comparison between active and placebo and are based on the logistic generalised linear mixed model (GLMM) using PROC GENMOD. The model includes the fixed effects treatment, visit, treatment by visit interaction assuming an unstructured correlation matrix. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 3.73

    Secondary: Patient Global Impression of Change 2

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    End point title
    		 Patient Global Impression of Change 2
    End point description
    Statistical analysis of PGIC response
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 GLMM
    Statistical analysis description
    Results display comparison between active and placebo and are based on the logistic generalised linear mixed model (GLMM) using PROC GENMOD. The model includes the fixed effects treatment, visit, treatment by visit interaction assuming an unstructured correlation matrix. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 4.93

    Secondary: Quality of life (EQ-5D-5L)

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    End point title
    		 Quality of life (EQ-5D-5L)
    End point description
    Change in EQ-5D-5L Mobility dimension
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 Proportional odds model
    Statistical analysis description
    Results display comparison between active and placebo and are based on a proportional odds model including treatment and baseline value. Variable tested at a 5% significance level
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.3

    Secondary: Quality of life (EQ-5D-5L) 2

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    End point title
    		 Quality of life (EQ-5D-5L) 2
    End point description
    Change in EQ-5D-5L Self-care dimension
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 Proportional odds model
    Statistical analysis description
    Results display comparison between active and placebo and are based on a proportional odds model including treatment and baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.37

    Secondary: Quality of life (EQ-5D-5L) 3

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    End point title
    		 Quality of life (EQ-5D-5L) 3
    End point description
    Change in EQ-5D-5L Usual activities dimension
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 Proportional odds model
    Statistical analysis description
    Results display comparison between active and placebo and are based on a proportional odds model including treatment and baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 1.54

    Secondary: Quality of life (EQ-5D-5L) 4

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    End point title
    		 Quality of life (EQ-5D-5L) 4
    End point description
    Change in EQ-5D-5L Pain/discomfort dimension
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 Proportional odds model
    Statistical analysis description
    Results display comparison between active and placebo and are based on a proportional odds model including treatment and baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 1.44

    Secondary: Quality of life (EQ-5D-5L) 5

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    End point title
    		 Quality of life (EQ-5D-5L) 5
    End point description
    Change in EQ-5D-5L Anxiety/depression dimension
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: n/a
    206
    197
    Statistical analysis title
    		 Proportional odds model
    Statistical analysis description
    Results display comparison between active and placebo and are based on a proportional odds model including treatment and baseline value. Variable tested at a 5% significance level.
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 Sign test
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.61

    Secondary: Quality of life (EQ-5D-5L) 6

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    End point title
    		 Quality of life (EQ-5D-5L) 6
    End point description
    Change in EQ VAS score
    End point type
    Secondary
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: score
        least squares mean (confidence interval 95%)
    8.88 (6.75 to 11.02)
    11.44 (9.28 to 13.60)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [17]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.6
         upper limit
    		 0.48
    Notes
    [17] - Variable tested at a 5% significance level

    Secondary: Leg pain W3

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    End point title
    		 Leg pain W3
    End point description
    Change in leg pain intensity on the NRS
    End point type
    Secondary
    End point timeframe
    From baseline to Week 3
    End point values
    		 Active Placebo
    Number of subjects analysed
    206
    197
    Units: Points
        least squares mean (confidence interval 95%)
    -1.66 (-1.92 to -1.40)
    -1.90 (-2.17 to -1.64)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    403
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [18]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 0.62
    Notes
    [18] - Variable tested at a 5% significance level

    Other pre-specified: Serum BDNF

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    End point title
    		 Serum BDNF
    End point description
    Change in serum BDNF level
    End point type
    Other pre-specified
    End point timeframe
    From baseline to Week 6
    End point values
    		 Active Placebo
    Number of subjects analysed
    180
    167
    Units: ng/ml
        least squares mean (confidence interval 95%)
    3.69 (-0.63 to 8.02)
    4.72 (0.23 to 9.21)
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    Active v Placebo
    Number of subjects included in analysis
    347
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [19]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.26
         upper limit
    		 5.22
    Notes
    [19] - Variable tested at a 5% significance level

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From informed consent date to the follow-up evaluation (30 days after the end of the treatment).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Active
    Reporting group description
    		 All subjects in active group who have taken at least one dose of the IMP.

    Reporting group title
    Placebo
    Reporting group description
    		 All subjects in placebo group who have taken at least one dose of the IMP.

    Serious adverse events
    		 Active Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 206 (0.49%)
    4 / 197 (2.03%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    1
    Injury, poisoning and procedural complications
    Lower limb fracture
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Respiratory tract infection
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Active Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    80 / 206 (38.83%)
    67 / 197 (34.01%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 206 (1.94%)
    1 / 197 (0.51%)
         occurrences all number
    6
    1
    Thrombosis
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Surgical and medical procedures
    Tooth extraction
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 206 (0.97%)
    3 / 197 (1.52%)
         occurrences all number
    2
    4
    Pain
         subjects affected / exposed
    2 / 206 (0.97%)
    1 / 197 (0.51%)
         occurrences all number
    2
    2
    Chest pain
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Malaise
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Swelling
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 206 (0.97%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Dyspnoea
         subjects affected / exposed
    0 / 206 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Dry throat
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    4 / 206 (1.94%)
    0 / 197 (0.00%)
         occurrences all number
    4
    0
    Agitation
         subjects affected / exposed
    2 / 206 (0.97%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Sleep disorder
         subjects affected / exposed
    0 / 206 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Anxiety
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Depressed mood
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Libido decreased
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    1 / 206 (0.49%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Blood glucose abnormal
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Prostatic specific antigen increased
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 206 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    3
    Contusion
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Forearm fracture
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Ligament sprain
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Stab wound
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Tendon rupture
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    3 / 206 (1.46%)
    0 / 197 (0.00%)
         occurrences all number
    3
    0
    Angina pectoris
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    7 / 206 (3.40%)
    3 / 197 (1.52%)
         occurrences all number
    7
    3
    Somnolence
         subjects affected / exposed
    6 / 206 (2.91%)
    1 / 197 (0.51%)
         occurrences all number
    7
    1
    Headache
         subjects affected / exposed
    4 / 206 (1.94%)
    2 / 197 (1.02%)
         occurrences all number
    5
    3
    Taste disorder
         subjects affected / exposed
    2 / 206 (0.97%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Lumbosacral radiculopathy
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    1
    2
    Balance disorder
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Migraine
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Paraesthesia
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Poor quality sleep
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Radicular pain
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Radiculopathy
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Tremor
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Leukopenia
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 206 (0.49%)
    2 / 197 (1.02%)
         occurrences all number
    1
    2
    Tinnitus
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    15 / 206 (7.28%)
    5 / 197 (2.54%)
         occurrences all number
    16
    5
    Nausea
         subjects affected / exposed
    8 / 206 (3.88%)
    4 / 197 (2.03%)
         occurrences all number
    8
    5
    Abdominal pain
         subjects affected / exposed
    4 / 206 (1.94%)
    0 / 197 (0.00%)
         occurrences all number
    4
    0
    Frequent bowel movements
         subjects affected / exposed
    4 / 206 (1.94%)
    0 / 197 (0.00%)
         occurrences all number
    4
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 206 (0.49%)
    2 / 197 (1.02%)
         occurrences all number
    1
    2
    Flatulence
         subjects affected / exposed
    0 / 206 (0.00%)
    3 / 197 (1.52%)
         occurrences all number
    0
    3
    Constipation
         subjects affected / exposed
    2 / 206 (0.97%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Dyspepsia
         subjects affected / exposed
    1 / 206 (0.49%)
    1 / 197 (0.51%)
         occurrences all number
    2
    1
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal hypermotility
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Teething
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Liver disorder
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 206 (0.00%)
    3 / 197 (1.52%)
         occurrences all number
    0
    3
    Hyperhidrosis
         subjects affected / exposed
    1 / 206 (0.49%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Pruritus
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    3 / 206 (1.46%)
    0 / 197 (0.00%)
         occurrences all number
    3
    0
    Dysuria
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    9 / 206 (4.37%)
    5 / 197 (2.54%)
         occurrences all number
    9
    7
    Arthralgia
         subjects affected / exposed
    1 / 206 (0.49%)
    4 / 197 (2.03%)
         occurrences all number
    1
    4
    Spinal pain
         subjects affected / exposed
    0 / 206 (0.00%)
    2 / 197 (1.02%)
         occurrences all number
    0
    2
    Muscle spasms
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Muscular weakness
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 206 (0.97%)
    3 / 197 (1.52%)
         occurrences all number
    3
    3
    COVID-19
         subjects affected / exposed
    1 / 206 (0.49%)
    3 / 197 (1.52%)
         occurrences all number
    1
    3
    Respiratory tract infection
         subjects affected / exposed
    1 / 206 (0.49%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 206 (0.49%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Viral infection
         subjects affected / exposed
    2 / 206 (0.97%)
    0 / 197 (0.00%)
         occurrences all number
    2
    0
    Coronavirus infection
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Cystitis
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Enterovirus infection
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Laryngitis
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Periodontitis
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Pneumonia
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Pulpitis dental
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Viral diarrhoea
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Increased appetite
         subjects affected / exposed
    1 / 206 (0.49%)
    1 / 197 (0.51%)
         occurrences all number
    1
    1
    Decreased appetite
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Glucose tolerance impaired
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 206 (0.49%)
    0 / 197 (0.00%)
         occurrences all number
    1
    0
    Hyperlipidaemia
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 206 (0.00%)
    1 / 197 (0.51%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Jun 2020
    Substantial amendment to address CA comments to original protocol.
    15 Apr 2021
    To add new countries. To revise statistical power.
    22 Sep 2022
    To incorporate interim analysis.

    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
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