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    Clinical Trial Results:
    A Phase 2 Placebo-Controlled, Double-Blind, Enriched Enrollment Randomized Withdrawal Study to Evaluate the Efficacy and Safety of BIIB074 (Vixotrigine) in Treating Pain Experienced by Subjects With Confirmed Small Fibre Neuropathy That Is Idiopathic or Associated With Diabetes Mellitus

    Summary
    EudraCT number
    		 2017-000991-27
    Trial protocol
    		 GB   CZ   GR   HU   ES   DK   BG   NL   IT  
    Global end of trial date
    12 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Apr 2022
    First version publication date
    25 Apr 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    802NP206
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03339336
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Biogen
    Sponsor organisation address
    225 Binney Street, Cambridge, United States, 02142
    Public contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
    Scientific contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Apr 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Apr 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the efficacy of BIIB074 in treating pain experienced by subjects with confirmed small fibre neuropathy (SFN) that was idiopathic or associated with diabetes mellitus. The secondary objectives were: (i) to evaluate the effect on worst pain, neuropathic pain quality, sleep interference due to pain, patient global impression, use of rescue medication, and SFN symptoms in subjects treated with BIIB074; (ii) to investigate the safety and tolerability of BIIB074 in subjects with SFN; and (iii) to characterise the pharmacokinetics (PK) of BIIB074 in subjects with SFN.
    Protection of trial subjects
    Written informed consent was obtained from each subject or subject’s legally authorised representative (e.g., legal guardian), as applicable, prior to evaluations performed for eligibility. Subjects or the subject’s legally authorised representative were given adequate time to review the information in the informed consent/assent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 May 2018
    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
    Poland: 46
    Country: Number of subjects enrolled
    France: 41
    Country: Number of subjects enrolled
    Czechia: 29
    Country: Number of subjects enrolled
    United Kingdom: 26
    Country: Number of subjects enrolled
    Netherlands: 24
    Country: Number of subjects enrolled
    Bulgaria: 23
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Hungary: 17
    Country: Number of subjects enrolled
    Italy: 17
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Switzerland: 3
    Country: Number of subjects enrolled
    Denmark: 3
    Worldwide total number of subjects
    265
    EEA total number of subjects
    231
    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)
    184
    From 65 to 84 years
    81
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects were enrolled at 68 investigative sites in Poland, France, Czech Republic, United Kingdom, Netherlands, Bulgaria, Germany, Hungary, Italy, Spain, Canada, Switzerland, and Denmark from 31 May 2018 to 08 March 2021.

    Pre-assignment
    Screening details
    		 The study consisted of screening period of up to 21 days, taper period of up to 14 days, 5-day washout period, and 4-week open-label (OL) run-in period. Number of subjects who completed OL run-in period is number of subjects who completed OL run-in period and were randomised to DB period.

    Period 1
    Period 1 title
    Open-Label (OL) Run-in Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 OL Period: BIIB074 350 milligrams (mg)
    Arm description
    		 Subjects received BIIB074 350 mg, tablets, orally, twice daily (BID), for 4 weeks of the open-label run-in period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BIIB074
    Investigational medicinal product code
    Other name
    Vixotrigine
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BIIB074 350 mg administered orally, BID for 4 weeks of the open-label run-in period.

    Number of subjects in period 1
    		OL Period: BIIB074 350 milligrams (mg)
    Started
    265
    Completed
    123
    Not completed
    142
         Consent withdrawn by subject
    7
         Adverse event
    14
         Lost to follow-up
    1
         Reason not specified
    18
         Lack of efficacy
    11
         Failed to meet randomisation criteria
    91
    Period 2
    Period 2 title
    Double-Blind (DB) Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 DB Period: Placebo
    Arm description
    		 Subjects received BIIB074-matching placebo, tablets, orally, BID, for 12 weeks of the double-blind period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BIIB074-matching placebo administered orally, BID, for 12 weeks of the double-blind period.

    Arm title
    		 DB Period: BIIB074 200 mg
    Arm description
    		 Subjects received BIIB074, 200 mg, tablets, orally, BID, for 12 weeks of the double-blind period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BIIB074
    Investigational medicinal product code
    Other name
    Vixotrigine
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BIIB074 200 mg administered orally, BID for 12 weeks of the double-blind period.

    Arm title
    		 DB Period: BIIB074 350 mg
    Arm description
    		 Subjects received BIIB074, 350 mg, tablets, orally, BID, for 12 weeks of the double-blind period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BIIB074
    Investigational medicinal product code
    Other name
    Vixotrigine
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    BIIB074 350 mg administered orally, BID for 12 weeks of the double-blind period.

    Number of subjects in period 2
    		DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Started
    41
    40
    42
    Completed
    34
    35
    38
    Not completed
    7
    5
    4
         Consent withdrawn by subject
    -
    1
    -
         Death
    1
    -
    -
         Adverse event
    2
    2
    -
         Reason not specified
    3
    2
    3
         Failed to meet randomisation criteria
    1
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    OL Period: BIIB074 350 milligrams (mg)
    Reporting group description
    		 Subjects received BIIB074 350 mg, tablets, orally, twice daily (BID), for 4 weeks of the open-label run-in period.

    Reporting group values
    		 OL Period: BIIB074 350 milligrams (mg) Total
    Number of subjects
    		 265 265
    Age Categorical
    Units: subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.8 ± 11.33 -
    Gender Categorical
    Units: subjects
        Female
    		 120 120
        Male
    		 145 145
    Race
    Units: Subjects
        Asian
    		 2 2
        Black or African American
    		 2 2
        White
    		 244 244
        Not reported due to confidentiality regulations
    		 16 16
        Other
    		 1 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 7 7
        Not Hispanic or Latino
    		 242 242
        Not reported due to confidentiality regulations
    		 16 16

    End points

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    End points reporting groups
    Reporting group title
    OL Period: BIIB074 350 milligrams (mg)
    Reporting group description
    		 Subjects received BIIB074 350 mg, tablets, orally, twice daily (BID), for 4 weeks of the open-label run-in period.
    Reporting group title
    DB Period: Placebo
    Reporting group description
    		 Subjects received BIIB074-matching placebo, tablets, orally, BID, for 12 weeks of the double-blind period.

    Reporting group title
    DB Period: BIIB074 200 mg
    Reporting group description
    		 Subjects received BIIB074, 200 mg, tablets, orally, BID, for 12 weeks of the double-blind period.

    Reporting group title
    DB Period: BIIB074 350 mg
    Reporting group description
    		 Subjects received BIIB074, 350 mg, tablets, orally, BID, for 12 weeks of the double-blind period.

    Subject analysis set title
    DB Period: Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received BIIB074-matching placebo, tablets, orally, BID, for 12 weeks of the double-blind period.

    Subject analysis set title
    DB Period: BIIB074 200 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received BIIB074, 200 mg, tablets, orally, BID, for 12 weeks of the double-blind period.

    Subject analysis set title
    DB Period: BIIB074 350 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received BIIB074, 350 mg, tablets, orally, BID, for 12 weeks of the double-blind period.

    Subject analysis set title
    DB Period: Placebo
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects received BIIB074-matching placebo, tablets, orally, BID, for 12 weeks of the double-blind period.

    Subject analysis set title
    DB Period: BIIB074 200 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects received BIIB074, 200 mg, tablets, orally, BID, for 12 weeks of the double-blind period.

    Subject analysis set title
    DB Period: BIIB074 350 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects received BIIB074, 350 mg, tablets, orally, BID, for 12 weeks of the double-blind period.

    Subject analysis set title
    OL Period: BIIB074 350 mg (PK Analysis)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received BIIB074 350 mg, tablets, orally, BID, for 4 weeks of the open-label run-in period.

    Primary: Change From Baseline to Double-Blind Week 12 in Mean Average Daily Pain (ADP) Score on the 11-point Numerical Rating Scale (NRS)

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    End point title
    		 Change From Baseline to Double-Blind Week 12 in Mean Average Daily Pain (ADP) Score on the 11-point Numerical Rating Scale (NRS)
    End point description
    The ADP score was based on an 11-point NRS, where, 0 = no pain and 10 = worst pain imaginable. Lower scores indicated less pain. Baseline was defined as the 5 days prior to the first dose of study treatment in the open-label run-in period (Day 1). The values reported are mean values. Full analysis set (FAS) included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment. Number of subjects analysed is the number of subjects evaluable in this end point.
    End point type
    Primary
    End point timeframe
    Baseline, DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    37
    38
    41
    Units: score on a scale
        least squares mean (standard error)
    -3.13 ± 0.311
    -3.99 ± 0.298
    -3.30 ± 0.292
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Analysis was performed using the mixed model for repeated measures (MMRM) model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0501
    Method
    		 MMRM
    Parameter type
    		 Least Squares (LS) mean difference
    Point estimate
    -0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.71
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6951
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.01
         upper limit
    		 0.68
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.426

    Secondary: Change from Randomisation to Double-Blind Week 12 in Mean ADP Score on the 11-point Numerical Rating Scale (NRS)

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    End point title
    		 Change from Randomisation to Double-Blind Week 12 in Mean ADP Score on the 11-point Numerical Rating Scale (NRS)
    End point description
    The ADP score was based on an 11-point NRS, where, 0 = no pain and 10 = worst pain imaginable. Lower scores indicated less pain. Baseline was defined as the 5 days prior to the first dose of study treatment in the open-label run-in period (Day 1). The values reported are mean values. FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment. Number of subjects analysed is the number of subjects evaluable in this end point.
    End point type
    Secondary
    End point timeframe
    Randomisation (Week 5), DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    37
    38
    41
    Units: score on a scale
        least squares mean (standard error)
    0.92 ± 0.321
    0.07 ± 0.305
    0.60 ± 0.298
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0575
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.74
         upper limit
    		 0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.444
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4708
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.19
         upper limit
    		 0.55
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.437

    Secondary: Change From Baseline to Double-Blind Week 12 in Mean Worst Daily Pain (WDP) Score on the 11-point Numerical Rating Scale (NRS)

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    End point title
    		 Change From Baseline to Double-Blind Week 12 in Mean Worst Daily Pain (WDP) Score on the 11-point Numerical Rating Scale (NRS)
    End point description
    The WDP score is based on an 11-point NRS, where, 0 = no pain and 10 = worst pain imaginable. Lower scores indicated less pain. Baseline was defined as the 5 days prior to the first dose of study treatment in the open-label run-in period (Day 1). The values reported are mean values. FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment. Number of subjects analysed is the number of subjects evaluable in this end point.
    End point type
    Secondary
    End point timeframe
    Baseline, DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    37
    38
    41
    Units: score on a scale
        least squares mean (standard error)
    -3.02 ± 0.334
    -3.95 ± 0.318
    -3.27 ± 0.311
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0455
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.85
         upper limit
    		 -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.461
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5835
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.15
         upper limit
    		 0.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.455

    Secondary: Change From Baseline to Double-Blind Week 12 in Mean Sleep Interference Numerical Rating Scale (S-NRS) Score

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    End point title
    		 Change From Baseline to Double-Blind Week 12 in Mean Sleep Interference Numerical Rating Scale (S-NRS) Score
    End point description
    The sleep interference score (due to SFN pain) is based on an 11-point NRS, where 0 = uninterrupted night’s sleep and 10 = worst sleep imaginable. Lower scores indicated less pain. Baseline was defined as the 5 days prior to the first dose of study treatment in the open-label run-in period (Day 1). The values reported are mean values. FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment. Number of subjects analysed is the number of subjects evaluable in this end point.
    End point type
    Secondary
    End point timeframe
    Baseline, DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    37
    38
    41
    Units: score on a scale
        least squares mean (standard error)
    -3.11 ± 0.303
    -3.58 ± 0.289
    -3.18 ± 0.282
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8545
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.89
         upper limit
    		 0.74
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.413
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2655
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.36
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42

    Secondary: Change from Baseline to Double-Blind Week 12 in Neuropathic Pain Symptom Inventory (NPSI) Total Score

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    End point title
    		 Change from Baseline to Double-Blind Week 12 in Neuropathic Pain Symptom Inventory (NPSI) Total Score
    End point description
    The NPSI is a self-rated questionnaire that includes 10 items corresponding to sensory descriptors (each rated on a numeric scale from 0 [no pain] to 10 [worst pain]) and 2 temporal items assessing pain duration and the number of pain paroxysms. The 10 sensory descriptor items are grouped into 5 dimensions (burning pain, pressing pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia). The total score for 10 sensory descriptor items ranges from 0 to 100. Baseline was defined as the last value prior to the first dose of study treatment in the open-label run-in period. FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment. Number of subjects analysed is the number of subjects evaluable in this end point.
    End point type
    Secondary
    End point timeframe
    Baseline, DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    27
    25
    29
    Units: score on a scale
        least squares mean (standard error)
    -22.1 ± 3.72
    -24.9 ± 3.61
    -23.4 ± 3.27
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.586
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.3
         upper limit
    		 7.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.23
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7906
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.2
         upper limit
    		 8.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.94

    Secondary: Change from Baseline to Double-Blind Week 12 in Neuropathic Pain Symptom Inventory (NPSI) Sum Score of Symptoms of Neuropathic Pain: Burning and Pressing

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    End point title
    		 Change from Baseline to Double-Blind Week 12 in Neuropathic Pain Symptom Inventory (NPSI) Sum Score of Symptoms of Neuropathic Pain: Burning and Pressing
    End point description
    The NPSI is a self-rated questionnaire that includes 10 items corresponding to sensory descriptors (each rated on a numeric scale from 0 [no pain] to 10 [worst pain]) and 2 temporal items assessing pain duration and the number of pain paroxysms. The 10 sensory descriptor items are grouped into 5 dimensions (burning pain, pressing pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia). The sum score for burning and pressing ranges from 0 to 20. Baseline was defined as the last value prior to the first dose of study treatment in the open-label run-in period. FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment. Number of subjects analysed is the number of subjects evaluable in this end point.
    End point type
    Secondary
    End point timeframe
    Baseline, DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    27
    25
    29
    Units: score on a scale
        least squares mean (standard error)
    -5.08 ± 0.829
    -5.56 ± 0.802
    -5.01 ± 0.723
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6852
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    -0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.79
         upper limit
    		 1.84
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.162
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9472
    Method
    		 MMRM
    Parameter type
    		 LS mean difference
    Point estimate
    0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.11
         upper limit
    		 2.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.095

    Secondary: Percentage of Subjects with at least a 2-Point Reduction from Baseline to Double-Blind Week 12 in Mean Average Daily Pain (ADP)

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    End point title
    		 Percentage of Subjects with at least a 2-Point Reduction from Baseline to Double-Blind Week 12 in Mean Average Daily Pain (ADP)
    End point description
    Baseline was defined as the 5 days prior to the first dose of study treatment in the open-label run-in period (Day 1). FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    40
    40
    41
    Units: percentage of subjects
        number (not applicable)
    55.0
    75.0
    70.7
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Logistic regression was adjusted for treatment, baseline ADP score and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.142
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 5.97
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Logistic regression was adjusted for treatment, baseline ADP score and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1019
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 6.43

    Secondary: Percentage of Subjects with at least a 30% Reduction from Baseline to Double-Blind Week 12 in Mean Average Daily Pain (ADP)

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    End point title
    		 Percentage of Subjects with at least a 30% Reduction from Baseline to Double-Blind Week 12 in Mean Average Daily Pain (ADP)
    End point description
    Baseline was defined as the 5 days prior to the first dose of study treatment in the open-label run-in period (Day 1). FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    40
    40
    41
    Units: percentage of subjects
        number (not applicable)
    52.5
    72.5
    68.3
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Logistic regression was adjusted for treatment, baseline ADP score and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1305
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 5.96
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Logistic regression was adjusted for treatment, baseline ADP score and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1212
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 5.99

    Secondary: Mean Daily Amount of Rescue Medication Used for SFN Pain During Double-Blind Period

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    End point title
    		 Mean Daily Amount of Rescue Medication Used for SFN Pain During Double-Blind Period
    End point description
    Use of rescue medication (paracetamol/acetaminophen) was monitored and dosage was recorded on a daily basis by the subject using an electronic Diary (eDiary). Baseline was defined as the 5 days prior to the first dose of study treatment in the open-label run-in period (Day 1). The values reported are mean values. FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Baseline, DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    40
    40
    41
    Units: milligrams per day
        arithmetic mean (standard deviation)
    83.08 ± 307.919
    99.10 ± 314.715
    24.87 ± 73.841
    No statistical analyses for this end point

    Secondary: Percentage of Patient Global Impression of Change (PGIC) Responders at Double-Blind Week 12

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    End point title
    		 Percentage of Patient Global Impression of Change (PGIC) Responders at Double-Blind Week 12
    End point description
    A PGIC responder is defined as someone who has answered 'very much improved' or 'much improved' on the PGIC questionnaire. PGIC is a 7-point scale that assesses a subject’s perceived change in overall status. Subjects rated their change as 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, or 7=very much worse relative to the start of the study (since taking study drug). FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Week 12 of the DB Period
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    40
    40
    41
    Units: percentage of responders
        number (not applicable)
    30.0
    37.5
    48.8
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Based on logistic regression adjusted for treatment and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7376
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 3.14
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Based on logistic regression adjusted for treatment and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.058
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 6.99

    Secondary: Change from Baseline to Double-Blind Week 12 in Brief Pain Inventory-Short Form (BPI-SF) Interference Score

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    End point title
    		 Change from Baseline to Double-Blind Week 12 in Brief Pain Inventory-Short Form (BPI-SF) Interference Score
    End point description
    The BPI-SF is a self-administered questionnaire for subjects to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function. Item 9 of the BPI-SF measures how much pain has interfered with 7 daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. Each activity is rated on a scale of 0 (does not interfere) to 10 (completely interferes). The BPI-SF interference score is calculated as the mean of the 7 interference item scores. Baseline was defined as the last value prior to the first dose of study treatment in the open-label run-in period. FAS included all randomised subjects who received at least one dose of double-blind study treatment and have at least 1 post-randomisation efficacy assessment. Number of subjects analysed is the number of subjects evaluable in this end point.
    End point type
    Secondary
    End point timeframe
    Baseline, DB Week 12
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    16
    7
    16
    Units: score on a scale
        least squares mean (standard error)
    -2.60 ± 0.668
    -2.01 ± 0.835
    -3.25 ± 0.606
    Statistical analysis title
    		 Placebo vs BIIB074 200 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 200 mg
    Number of subjects included in analysis
    23
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5863
    Method
    		 MMRM
    Parameter type
    		 LS Mean difference
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.65
         upper limit
    		 2.84
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.081
    Statistical analysis title
    		 Placebo vs BIIB074 350 mg
    Statistical analysis description
    Analysis was performed using the MMRM model, fitting treatment timepoint, treatment*timepoint interaction, baseline score, baseline score*timepoint interaction and SFN etiology.
    Comparison groups
    DB Period: Placebo v DB Period: BIIB074 350 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4791
    Method
    		 MMRM
    Parameter type
    		 LS Mean difference
    Point estimate
    -0.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.52
         upper limit
    		 1.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.903

    Secondary: Percentage of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) During Double-Blind Period

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    End point title
    		 Percentage of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) During Double-Blind Period
    End point description
    An AE was any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE was any untoward medical occurrence that at any dose resulted in death; in the view of the investigator, placed the subject at immediate risk of death (a life-threatening event); required inpatient hospitalisation or prolongation of existing hospitalisation; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect. Double-blind (DB) safety population included all randomised subjects who received at least 1 dose of DB treatment.
    End point type
    Secondary
    End point timeframe
    From randomisation of subjects who received at least 1 dose of double-blind treatment to end of study (up to approximately 140 weeks)
    End point values
    		 DB Period: Placebo DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    41
    40
    41
    Units: percentage of subjects
    number (not applicable)
        AEs
    61.0
    47.5
    43.9
        SAEs
    9.8
    2.5
    2.4
    No statistical analyses for this end point

    Secondary: Mean Plasma Concentration During Open-Label Period

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    End point title
    		 Mean Plasma Concentration During Open-Label Period
    End point description
    OL pharmacokinetic (PK) population included OL safety subjects who have at least one post-baseline PK concentration measurement. Here, ”n” signifies number of subjects evaluated at specific timepoint in this end point.
    End point type
    Secondary
    End point timeframe
    Pre-dose and 2 hours post-dose on open-label (OL) Day 1, OL Week 2; pre-dose on OL Week 4 and OL follow-up visit
    End point values
    		 OL Period: BIIB074 350 mg (PK Analysis)
    Number of subjects analysed
    264
    Units: nanograms per millilitre (ng/mL)
    arithmetic mean (standard deviation)
        OL Day 1: Predose (n=258)
    36.39 ± 419.388
        OL Day 1: 2 Hours Post-dose (n=255)
    2974.93 ± 1194.403
        OL Week 2: Predose (n=234)
    2337.68 ± 1299.573
        OL Week 2: 2 Hours Post-dose (n=234)
    5286.11 ± 1869.361
        OL Week 4: Predose (n=207)
    2159.29 ± 1043.990
        OL Follow-up visit: Predose (n=2)
    2165.75 ± 3046.570
    No statistical analyses for this end point

    Secondary: Mean Plasma Concentration During Double-Blind Period

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    End point title
    		 Mean Plasma Concentration During Double-Blind Period
    End point description
    DB PK population included DB safety subjects who have at least one post-randomisation PK concentration measurement. Here, ”n” signifies number of subjects evaluated at specific timepoint in this end point.
    End point type
    Secondary
    End point timeframe
    Pre-dose and 2 hours post-dose on double-blind (DB) Day 1, DB Week 4, DB Week 8, DB Week 12; pre-dose on DB follow-up visit
    End point values
    		 DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg
    Number of subjects analysed
    40
    41
    Units: ng/mL
    arithmetic mean (standard deviation)
        DB Day 1: Predose (n=37,41)
    2332.38 ± 1058.584
    2105.78 ± 938.915
        DB Day 1: 2 Hours Post-dose (n=39,40)
    4031.64 ± 1728.923
    4817.95 ± 1951.975
        DB Week 4: Predose (n=37,38)
    1476.57 ± 811.089
    2007.55 ± 1076.381
        DB Week 4: 2 Hours Post-dose (n=39,38)
    3057.69 ± 872.572
    4771.23 ± 1800.318
        DB Week 8: Predose (n=35,37)
    1272.58 ± 608.584
    2158.51 ± 831.852
        DB Week 8: 2 Hours Post-dose (n=34,38)
    2976.65 ± 1022.002
    4992.63 ± 1750.338
        DB Week 12: Predose (n=32,31)
    1342.66 ± 634.202
    2250.81 ± 1027.830
        DB Week 12: 2 Hours Post-dose (n=31,37)
    3076.13 ± 893.203
    4789.19 ± 1637.541
        DB Follow-up visit: Predose (n=7,9)
    300.81 ± 673.591
    108.87 ± 221.032
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From screening to the end of study (up to approximately 159 weeks)
    Adverse event reporting additional description
    OL safety population included all enrolled subjects who received at least 1 dose of treatment with BIIB074 during the OL run-in period. DB safety population included all randomised subjects who received at least 1 dose of DB treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    DB Period: BIIB074 200 mg
    Reporting group description
    		 Subjects received BIIB074, 200 mg, tablets, orally, BID, for 12 weeks of the double-blind period.

    Reporting group title
    DB Period: BIIB074 350 mg
    Reporting group description
    		 Subjects received BIIB074, 350 mg, tablets, orally, BID, for 12 weeks of the double-blind period.

    Reporting group title
    DB Period: Placebo
    Reporting group description
    		 Subjects received BIIB074-matching placebo, tablets, orally, BID, for 12 weeks of the double-blind period.

    Reporting group title
    OL Period: BIIB074 350 mg
    Reporting group description
    		 Subjects received BIIB074 350 mg, tablets, orally, BID, for 4 weeks of the open-label run-in period.

    Serious adverse events
    		 DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg DB Period: Placebo OL Period: BIIB074 350 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 41 (2.44%)
    4 / 41 (9.76%)
    5 / 265 (1.89%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 265 (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
    Atrial fibrillation
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 265 (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 arrest
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 265 (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
    Ventricular fibrillation
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 265 (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
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 265 (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
    Gastrointestinal disorders
    Pancreatitis acute
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 265 (0.38%)
         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
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 265 (0.38%)
         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
    Pulmonary embolism
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 265 (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
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 265 (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
    Focal peritonitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 265 (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 pneumonia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 265 (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 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Electrolyte imbalance
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 265 (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
    		 DB Period: BIIB074 200 mg DB Period: BIIB074 350 mg DB Period: Placebo OL Period: BIIB074 350 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 40 (15.00%)
    7 / 41 (17.07%)
    12 / 41 (29.27%)
    57 / 265 (21.51%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 40 (0.00%)
    3 / 41 (7.32%)
    0 / 41 (0.00%)
    4 / 265 (1.51%)
         occurrences all number
    0
    3
    0
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    25 / 265 (9.43%)
         occurrences all number
    0
    0
    0
    28
    Headache
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 41 (2.44%)
    5 / 41 (12.20%)
    25 / 265 (9.43%)
         occurrences all number
    1
    1
    11
    32
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 41 (4.88%)
    4 / 41 (9.76%)
    6 / 265 (2.26%)
         occurrences all number
    1
    2
    5
    8
    Nausea
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 41 (0.00%)
    3 / 41 (7.32%)
    11 / 265 (4.15%)
         occurrences all number
    0
    0
    4
    12
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 41 (2.44%)
    1 / 41 (2.44%)
    1 / 265 (0.38%)
         occurrences all number
    2
    1
    1
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 41 (4.88%)
    3 / 41 (7.32%)
    6 / 265 (2.26%)
         occurrences all number
    2
    2
    5
    6
    Urinary tract infection
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 41 (0.00%)
    3 / 41 (7.32%)
    3 / 265 (1.13%)
         occurrences all number
    2
    0
    3
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 May 2017
    To clarify that pregnancy of a female partner should not impact the study status of a male subject during his participation in the study.
    06 Sep 2017
    To change the study design to include a separate washout period prior to the open-label run-in period during which no pain medications are allowed. The taper and washout periods were added to the screening period for a total duration of up to 6 weeks.
    06 Jun 2018
    To update the diagnostic criteria for small fiber neuropathy (SFN) in the inclusion criteria.
    23 Jul 2019
    To update the details of the 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.
    Sponsor decision to close study early; not due to safety concerns.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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