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    Clinical Trial Results:
    A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Efficacy and Safety of VX-765 in Subjects With Treatment-Resistant Partial Epilepsy With a 24-Week Open-Label Extension

    Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
    Summary
    EudraCT number
    2011-004156-19
    Trial protocol
    DE   CZ   AT   HU   GB   FI  
    Global end of trial date
    24 Sep 2013

    Results information
    Results version number
    v1(current)
    This version publication date
    13 Jul 2016
    First version publication date
    13 Jul 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    VX11-765-402
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01501383
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Vertex Pharmaceuticals Incorporated
    Sponsor organisation address
    50 Northern Avenue, Boston, Massachusetts, United States, 02210-1862
    Public contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
    Scientific contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.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
    18 Oct 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Sep 2013
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Part A: To evaluate the efficacy of VX-765 to treat seizures in subjects with treatment-resistant partial epilepsy and to evaluate the safety and tolerability of VX-765 in subjects with treatment-resistant partial epilepsy; Part B: To evaluate the safety and tolerability of long term VX-765 treatment in subjects with treatment-resistant partial epilepsy.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    20 Dec 2011
    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
    United States: 48
    Country: Number of subjects enrolled
    Germany: 7
    Worldwide total number of subjects
    55
    EEA total number of subjects
    7
    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)
    55
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    An administrative decision was made by Vertex Pharmaceuticals Incorporated (Vertex) to stop the enrollment of subjects during the conduct of this study and to postpone further clinical development of VX-765 for the treatment of epilepsy. A total of 55 subjects were randomized in to study.

    Period 1
    Period 1 title
    Part A: Double Blind Treatment Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part A Placebo
    Arm description
    Placebo matched to VX-765 tablet three times daily (TID) up to Week 13.
    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 matched to VX-765 tablet TID.

    Arm title
    Part A VX-765 300 mg
    Arm description
    VX-765 300 milligram(mg) tablet TID up to Week 13.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-765
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-765 tablet TID.

    Arm title
    Part A VX-765 600 mg
    Arm description
    VX-765 600 mg tablet TID up to Week 13.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-765
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-765 tablet TID.

    Arm title
    Part A VX-765 900 mg
    Arm description
    VX-765 900 mg tablet TID up to Week 13.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-765
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-765 tablet TID.

    Arm title
    Part A VX-765 1200 mg
    Arm description
    VX-765 1200 mg tablet TID up to Week 13.
    Arm type
    Experimental

    Investigational medicinal product name
    VX-765
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-765 1200 mg tablet TID.

    Number of subjects in period 1
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Started
    12
    10
    11
    11
    11
    Completed
    10
    8
    11
    9
    11
    Not completed
    2
    2
    0
    2
    0
         Subject Refused Further Dosing (Not Due to AE)
    -
    -
    -
    1
    -
         Consent withdrawn by subject
    -
    -
    -
    1
    -
         Adverse Events
    2
    2
    -
    -
    -
    Period 2
    Period 2 title
    Part B: Open-label Extension Period
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part A Placebo to Part B VX-765 600/900/1200 mg
    Arm description
    Subjects who received placebo matched to VX-765 tablet (TID) up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).
    Arm type
    Experimental

    Investigational medicinal product name
    VX-765
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-765 tablet TID.

    Arm title
    Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg
    Arm description
    Subjects who received VX-765 300 mg tablet TID up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).
    Arm type
    Experimental

    Investigational medicinal product name
    VX-765
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-765 tablet TID.

    Arm title
    Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg
    Arm description
    Subjects who received VX-765 600 mg tablet TID up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).
    Arm type
    Experimental

    Investigational medicinal product name
    VX-765
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-765 tablet TID.

    Arm title
    Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg
    Arm description
    Subjects who received VX-765 900 mg tablet TID up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).
    Arm type
    Experimental

    Investigational medicinal product name
    VX-765
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-765 tablet TID.

    Arm title
    Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Arm description
    Subjects who received VX-765 1200 mg tablet TID up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).
    Arm type
    Experimental

    Investigational medicinal product name
    VX-765
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    VX-765 tablet TID.

    Number of subjects in period 2 [1]
    Part A Placebo to Part B VX-765 600/900/1200 mg Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Started
    10
    8
    9
    9
    10
    Completed
    6
    7
    7
    8
    6
    Not completed
    4
    1
    2
    1
    4
         Subject Refused Further Dosing (Not Due to AE)
    1
    -
    -
    -
    2
         Subject Withdrew Consent
    -
    1
    1
    -
    -
         Physician Decision
    1
    -
    -
    1
    1
         Adverse Events
    2
    -
    1
    -
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Only subjects who completed the Part A Treatment Period and elected to enter Part B and met Part B eligibility criteria were included in Part B.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part A Placebo
    Reporting group description
    Placebo matched to VX-765 tablet three times daily (TID) up to Week 13.

    Reporting group title
    Part A VX-765 300 mg
    Reporting group description
    VX-765 300 milligram(mg) tablet TID up to Week 13.

    Reporting group title
    Part A VX-765 600 mg
    Reporting group description
    VX-765 600 mg tablet TID up to Week 13.

    Reporting group title
    Part A VX-765 900 mg
    Reporting group description
    VX-765 900 mg tablet TID up to Week 13.

    Reporting group title
    Part A VX-765 1200 mg
    Reporting group description
    VX-765 1200 mg tablet TID up to Week 13.

    Reporting group values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg Total
    Number of subjects
    12 10 11 11 11 55
    Age categorical
    Units: Subjects
    Age continuous
    Due to EudraCT limitations, it is not possible to report Mean (SD) for total column.
    Units: years
        arithmetic mean (standard deviation)
    43.3 ± 12.26 35.2 ± 14.27 37.6 ± 10.03 35.4 ± 10.58 40.7 ± 13.75 -
    Gender categorical
    Units: Subjects
        Female
    6 6 5 4 6 27
        Male
    6 4 6 7 5 28

    End points

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    End points reporting groups
    Reporting group title
    Part A Placebo
    Reporting group description
    Placebo matched to VX-765 tablet three times daily (TID) up to Week 13.

    Reporting group title
    Part A VX-765 300 mg
    Reporting group description
    VX-765 300 milligram(mg) tablet TID up to Week 13.

    Reporting group title
    Part A VX-765 600 mg
    Reporting group description
    VX-765 600 mg tablet TID up to Week 13.

    Reporting group title
    Part A VX-765 900 mg
    Reporting group description
    VX-765 900 mg tablet TID up to Week 13.

    Reporting group title
    Part A VX-765 1200 mg
    Reporting group description
    VX-765 1200 mg tablet TID up to Week 13.
    Reporting group title
    Part A Placebo to Part B VX-765 600/900/1200 mg
    Reporting group description
    Subjects who received placebo matched to VX-765 tablet (TID) up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).

    Reporting group title
    Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg
    Reporting group description
    Subjects who received VX-765 300 mg tablet TID up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).

    Reporting group title
    Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg
    Reporting group description
    Subjects who received VX-765 600 mg tablet TID up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).

    Reporting group title
    Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg
    Reporting group description
    Subjects who received VX-765 900 mg tablet TID up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).

    Reporting group title
    Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Reporting group description
    Subjects who received VX-765 1200 mg tablet TID up to Week 13 in Part A and met Part B eligibility criteria, received VX-765 900 mg TID for 12 weeks (from end of Week 13 through Week 25) followed by VX-765 600 mg or 900 mg or 1200 mg as per Investigator discretion for 12 weeks (Week 26 through Week 37).

    Primary: Part A: Percent Reduction in Weekly Seizure Frequency During Part A Late Treatment Period Compared to Part A Baseline

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    End point title
    Part A: Percent Reduction in Weekly Seizure Frequency During Part A Late Treatment Period Compared to Part A Baseline
    End point description
    Percent reduction in weekly seizure frequency refers to the percent reduction in the (average) weekly seizure frequency occurring during a target time period relative to the Baseline Period in Part A. Seizure frequency was derived from observed seizure frequency data by normalizing the observed data to a 7-day period, with no imputation for gaps in reporting or early discontinuations. Analysis was performed on Part A Full Analysis Set (FAS) (defined as all randomized subjects who received at least 1 dose of study drug [VX-765 or placebo] and had at least 1 treatment-period efficacy measurement) subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 5 to Week 9), in each treatment group.
    End point type
    Primary
    End point timeframe
    Part A baseline, Part A late treatment period (Week 5 through Week 13)
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    10
    9
    11
    10
    11
    Units: percent change
        median (confidence interval 95%)
    -3.63 (-37.77 to 20.8)
    -13.64 (-45.91 to 18.18)
    -14.06 (-42.07 to -2.41)
    16.16 (-27.96 to 102.41)
    -25.3 (-58.88 to 1.71)
    Statistical analysis title
    Jonckheere-Terpstra Trend Comparison
    Comparison groups
    Part A Placebo v Part A VX-765 300 mg v Part A VX-765 600 mg v Part A VX-765 900 mg v Part A VX-765 1200 mg
    Number of subjects included in analysis
    51
    Analysis specification
    Post-hoc
    Analysis type
    other
    P-value
    = 0.5223
    Method
    Jonckheere-Terpstra Trend Test
    Confidence interval

    Primary: Part A: Percentage of Subjects with 50% or Greater Reduction in Weekly Seizure Frequency During Part A Late Treatment Period Compared to Part A Baseline

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    End point title
    Part A: Percentage of Subjects with 50% or Greater Reduction in Weekly Seizure Frequency During Part A Late Treatment Period Compared to Part A Baseline
    End point description
    The 95% confidence interval (CI) examine the >=50% response rate proportion CI for each treatment group, separately. This test served as an additional method (unadjusted by baseline seizure frequency) to examine the proportions of subjects with >=50% reduction in seizure frequency during the Late Treatment Period. Analysis was performed on Part A FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 5 to Week 9), in each treatment group.
    End point type
    Primary
    End point timeframe
    Part A baseline, Part A late treatment period (Week 5 through Week 13)
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    10
    9
    11
    10
    11
    Units: percentage of subjects
        number (confidence interval 95%)
    20 (2.5 to 55.6)
    22.2 (2.8 to 60)
    27.3 (6 to 61)
    0 (0 to 30.9)
    36.4 (10.9 to 69.2)
    Statistical analysis title
    Cochran Armitage Trend Test
    Statistical analysis description
    P value for linear trend test between the placebo group and the 4 sequentially dose-escalated VX-765 treatment groups.
    Comparison groups
    Part A Placebo v Part A VX-765 300 mg v Part A VX-765 600 mg v Part A VX-765 900 mg v Part A VX-765 1200 mg
    Number of subjects included in analysis
    51
    Analysis specification
    Post-hoc
    Analysis type
    other
    P-value
    = 0.8147
    Method
    Cochran Armitage Trend Test
    Confidence interval

    Primary: Part A: Safety and Tolerability – Percentage of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    Part A: Safety and Tolerability – Percentage of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) [1]
    End point description
    Treatment-emergent AEs (TEAEs), referred to as AEs, for Part A were defined as any AEs that were reported or worsened on or after the start of study drug (1) through the Part A Safety Follow-up Visit for subjects who were not eligible or did not elect to enter the OLE, and (2) through the last day of the Part A Treatment Period for subjects who entered the OLE. Results are reported separately for treatment period (TP) and safety follow-up period (SFUP). The Safety Set for Part A included all subjects who received at least 1 dose of study drug. The number of subjects for each time-point are specified as “n”.
    End point type
    Primary
    End point timeframe
    Part A: Start of study drug through safety follow-up (up to Week 17)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for safety endpoint.
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    12
    10
    11
    11
    11
    Units: percentage of subjects
    number (not applicable)
        TP: Subjects with AEs (n = 12, 10, 11, 11, 11)
    83.3
    50
    72.7
    54.5
    72.2
        TP: Subjects with SAEs (n = 12, 10, 11, 11, 11)
    0
    0
    9.1
    0
    0
        SFUP: Subjects with AEs (n = 2, 2, 2, 2, 1)
    50
    100
    50
    0
    0
        SFUP: Subjects with SAEs (n = 2, 2, 2, 2, 1)
    50
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Part B: Safety and Tolerability – Percentage of Subjects with AEs and SAEs

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    End point title
    Part B: Safety and Tolerability – Percentage of Subjects with AEs and SAEs [2]
    End point description
    TEAEs for Part B were defined as AEs that were reported or worsened on or after the start of Part B study drug dosing through the Part B Safety Follow-up Visit. Results are reported separately for treatment period (TP) and safety follow-up period (SFUP). The Safety Set for Part B included all subjects who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Part B: Start of study drug through safety follow-up (up to Week 41)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for safety endpoint.
    End point values
    Part A Placebo to Part B VX-765 600/900/1200 mg Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Number of subjects analysed
    10
    7
    8
    9
    9
    Units: percentage of subjects
    number (not applicable)
        TP: Subjects with AEs
    80
    71.4
    87.5
    77.8
    66.7
        TP: Subjects with SAEs
    10
    0
    0
    0
    0
        SFUP: Subjects with AEs
    10
    57.1
    37.5
    11.1
    11.1
        SFUP: Subjects with SAEs
    0
    14.3
    12.5
    0
    0
    No statistical analyses for this end point

    Secondary: Part A: Percentage of Subjects Who Were Seizure-Free During the Part A Late Treatment Period

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    End point title
    Part A: Percentage of Subjects Who Were Seizure-Free During the Part A Late Treatment Period
    End point description
    Analysis was performed on Part A FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 5 to Week 9), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part A late treatment period (Week 5 through Week 13)
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    10
    9
    11
    10
    11
    Units: percentage of subjects
        number (confidence interval 95%)
    0 (0 to 30.9)
    11.1 (0.3 to 48.3)
    0 (0 to 28.5)
    0 (0 to 30.9)
    0 (0 to 28.5)
    No statistical analyses for this end point

    Secondary: Part A: Percent Reduction in Weekly Seizure Frequency During Entire Part A Treatment Period Compared to Part A Baseline

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    End point title
    Part A: Percent Reduction in Weekly Seizure Frequency During Entire Part A Treatment Period Compared to Part A Baseline
    End point description
    Percent reduction in weekly seizure frequency refers to the percent reduction in the (average) weekly seizure frequency occurring during a target time period relative to the Baseline Period in Part A. Seizure frequency was derived from observed seizure frequency data by normalizing the observed data to a 7-day period, with no imputation for gaps in reporting or early discontinuations. Analysis was performed on Part A FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 1 to Week 7), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part A baseline, Part A entire treatment period (through Week 13)
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    11
    9
    11
    11
    11
    Units: percent change
        median (confidence interval 95%)
    -1.48 (-25.61 to 21.9)
    -0.16 (-40.74 to 20.89)
    -10.33 (-35.84 to 2.54)
    17.06 (-13.97 to 67.59)
    -5.64 (-50.22 to 6.92)
    No statistical analyses for this end point

    Secondary: Part A: Percentage of Subjects with 50% or Greater Reduction in Weekly Seizure Frequency During Part A Entire Treatment Period Compared to Part A Baseline

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    End point title
    Part A: Percentage of Subjects with 50% or Greater Reduction in Weekly Seizure Frequency During Part A Entire Treatment Period Compared to Part A Baseline
    End point description
    Analysis was performed on Part A FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 1 to Week 7), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part A baseline, Part A entire treatment period (through Week 13)
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    11
    9
    11
    11
    11
    Units: percentage of subjects
        number (confidence interval 95%)
    18.2 (2.3 to 51.8)
    11.1 (0.3 to 48.3)
    9.1 (0.2 to 41.3)
    0 (0 to 28.5)
    36.4 (10.9 to 69.2)
    No statistical analyses for this end point

    Secondary: Part A: Percentage of Subjects Who Were Seizure-Free During the Part A Entire Treatment Period

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    End point title
    Part A: Percentage of Subjects Who Were Seizure-Free During the Part A Entire Treatment Period
    End point description
    Analysis was performed on Part A FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 1 to Week 7), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part A entire treatment period (through Week 13)
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    11
    9
    11
    11
    11
    Units: percentage of subjects
        number (confidence interval 95%)
    0 (0 to 28.5)
    0 (0 to 33.6)
    0 (0 to 28.5)
    0 (0 to 28.5)
    0 (0 to 28.5)
    No statistical analyses for this end point

    Secondary: Part A: Maximum Number of Consecutive Days that Subjects did not have Seizures at any time During the Part A Late Treatment Period

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    End point title
    Part A: Maximum Number of Consecutive Days that Subjects did not have Seizures at any time During the Part A Late Treatment Period
    End point description
    Analysis was performed on Part A FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 5 to Week 9), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part A late treatment period (Week 5 through Week 13)
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    10
    9
    11
    10
    11
    Units: days
        arithmetic mean (standard deviation)
    10.6 ± 11.26
    13.3 ± 19.59
    12.2 ± 7.57
    9.8 ± 5.73
    12.2 ± 9.69
    No statistical analyses for this end point

    Secondary: Part A: Maximum Number of Consecutive Days that Subjects did not have Seizures at any time During the Part A Entire Treatment Period

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    End point title
    Part A: Maximum Number of Consecutive Days that Subjects did not have Seizures at any time During the Part A Entire Treatment Period
    End point description
    Analysis was performed on Part A FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 1 to Week 7), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part A entire treatment period (through Week 13)
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    11
    9
    11
    11
    11
    Units: days
        arithmetic mean (standard deviation)
    10.7 ± 12.38
    15.7 ± 25.98
    12.9 ± 7.49
    12 ± 7.4
    12.5 ± 9.66
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK) of VX-765, VRT-043198, and Concomitant Antiepileptic Drug (AED) Levels in blood

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    End point title
    Pharmacokinetics (PK) of VX-765, VRT-043198, and Concomitant Antiepileptic Drug (AED) Levels in blood
    End point description
    The PK analyses are omitted per the FDA Guidance Document “Submission of Abbreviated Reports and Synopses in Support of Marketing Applications".
    End point type
    Secondary
    End point timeframe
    NA
    End point values
    Part A Placebo Part A VX-765 300 mg Part A VX-765 600 mg Part A VX-765 900 mg Part A VX-765 1200 mg
    Number of subjects analysed
    0 [3]
    0 [4]
    0 [5]
    0 [6]
    0 [7]
    Units: NA
    Notes
    [3] - The PK analyses are omitted as specified in endpoint description.
    [4] - The PK analyses are omitted as specified in endpoint description.
    [5] - The PK analyses are omitted as specified in endpoint description.
    [6] - The PK analyses are omitted as specified in endpoint description.
    [7] - The PK analyses are omitted as specified in endpoint description.
    No statistical analyses for this end point

    Secondary: Part B: Percent Reduction in Weekly Seizure Frequency During Part B Entire Treatment Period Compared to Part A Baseline

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    End point title
    Part B: Percent Reduction in Weekly Seizure Frequency During Part B Entire Treatment Period Compared to Part A Baseline
    End point description
    Percent reduction in weekly seizure frequency refers to the percent reduction in the (average) weekly seizure frequency occurring during a target time period relative to the Baseline Period in Part A. Seizure frequency was derived from observed seizure frequency data by normalizing the observed data to a 7-day period, with no imputation for gaps in reporting or early discontinuations. Analysis was performed on Part B FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 14 to Week 25), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part A Baseline, Part B entire treatment period (end of Week 13 through Week 37)
    End point values
    Part A Placebo to Part B VX-765 600/900/1200 mg Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Number of subjects analysed
    9
    7
    8
    9
    8
    Units: percent change
        arithmetic mean (standard deviation)
    -15.04 ± 30.386
    -33.27 ± 46.353
    -11.21 ± 31.476
    14.28 ± 47.684
    -21.26 ± 38.954
    No statistical analyses for this end point

    Secondary: Part B: Percentage of Subjects with 50% or Greater Reduction in Weekly Seizure Frequency During Part B Entire Treatment Period Compared to Part A Baseline

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    End point title
    Part B: Percentage of Subjects with 50% or Greater Reduction in Weekly Seizure Frequency During Part B Entire Treatment Period Compared to Part A Baseline
    End point description
    Analysis was performed on Part B FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 14 to Week 25), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part A Baseline, Part B entire treatment period (end of Week 13 through Week 37)
    End point values
    Part A Placebo to Part B VX-765 600/900/1200 mg Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Number of subjects analysed
    9
    7
    8
    9
    8
    Units: percentage of subjects
        number (confidence interval 95%)
    22.2 (0 to 49.4)
    42.9 (6.2 to 79.5)
    25 (0 to 55)
    0 (0 to 0)
    25 (0 to 55)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with 75% or Greater Reduction in Weekly Seizure Frequency During Part B Entire Treatment Period Compared to Part A Baseline

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    End point title
    Percentage of Subjects with 75% or Greater Reduction in Weekly Seizure Frequency During Part B Entire Treatment Period Compared to Part A Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Part A Baseline, Part B entire treatment period (end of Week 13 through Week 37)
    End point values
    Part A Placebo to Part B VX-765 600/900/1200 mg Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Number of subjects analysed
    0 [8]
    0 [9]
    0 [10]
    0 [11]
    0 [12]
    Units: percentage of subjects
        number (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [8] - Analysis was not performed due to early study termination.
    [9] - Analysis was not performed due to early study termination.
    [10] - Analysis was not performed due to early study termination.
    [11] - Analysis was not performed due to early study termination.
    [12] - Analysis was not performed due to early study termination.
    No statistical analyses for this end point

    Secondary: Part B: Percentage of Subjects Who Were Seizure-Free During the Part B Entire Treatment Period

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    End point title
    Part B: Percentage of Subjects Who Were Seizure-Free During the Part B Entire Treatment Period
    End point description
    Analysis was performed on Part B FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 14 to Week 25), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part B entire treatment period (end of Week 13 through Week 37)
    End point values
    Part A Placebo to Part B VX-765 600/900/1200 mg Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Number of subjects analysed
    9
    7
    8
    9
    8
    Units: percentage of subjects
        number (not applicable)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Part B: Number of Subjects in Categories of Total Number of Days Seizure-free During the Part B Entire Treatment Period

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    End point title
    Part B: Number of Subjects in Categories of Total Number of Days Seizure-free During the Part B Entire Treatment Period
    End point description
    Number of subjects are reported in categories of total number of days seizure-free. Analysis was performed on Part B FAS subjects who met the minimum seizure-log data criteria of at least half of the time period (Week 14 to Week 25), in each treatment group.
    End point type
    Secondary
    End point timeframe
    Part B entire treatment period (end of Week 13 through Week 37)
    End point values
    Part A Placebo to Part B VX-765 600/900/1200 mg Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Number of subjects analysed
    9
    7
    8
    9
    8
    Units: number of subjects
        >=150 Days
    0
    3
    0
    1
    2
        >=120 Days
    4
    5
    3
    4
    4
        >=100 Days
    4
    5
    6
    5
    5
        >=90 Days
    4
    6
    6
    7
    5
        >=80 Days
    5
    6
    6
    7
    5
        >=70 Days
    5
    6
    7
    7
    6
        >=60 Days
    7
    6
    7
    8
    7
        >=50 Days
    7
    6
    7
    8
    7
        >=40 Days
    7
    6
    8
    8
    7
        >=30 Days
    8
    6
    8
    8
    7
        >=20 Days
    8
    6
    8
    8
    7
        >=10 Days
    9
    6
    8
    8
    7
        >0 Days
    9
    7
    8
    9
    8
        0 Days
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Part B: Percent Increase in Weekly Seizure-Free Days During the Part B Entire Treatment Period Compared to the Part A Baseline Period

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    End point title
    Part B: Percent Increase in Weekly Seizure-Free Days During the Part B Entire Treatment Period Compared to the Part A Baseline Period
    End point description
    End point type
    Secondary
    End point timeframe
    NA
    End point values
    Part A Placebo to Part B VX-765 600/900/1200 mg Part A VX-765 300 mg to Part B VX-765 600/900/1200 mg Part A VX-765 600 mg to Part B VX-765 600/900/1200 mg Part A VX-765 900 mg to Part B VX-765 600/900/1200 mg Part A VX-765 1200 mg to Part B VX-765 600/900/1200 mg
    Number of subjects analysed
    0 [13]
    0 [14]
    0 [15]
    0 [16]
    0 [17]
    Units: NA
        number (not applicable)
    Notes
    [13] - Analysis was not performed due to early study termination.
    [14] - Analysis was not performed due to early study termination.
    [15] - Analysis was not performed due to early study termination.
    [16] - Analysis was not performed due to early study termination.
    [17] - Analysis was not performed due to early study termination.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Part A: Start of study drug through safety follow-up (up to Week 17); Part B: Start of study drug through safety follow-up (up to Week 41)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    14.1
    Reporting groups
    Reporting group title
    Placebo - Part A
    Reporting group description
    Placebo matched to VX-765 tablets TID up to Week 13.

    Reporting group title
    VX-765 300 mg - Part A
    Reporting group description
    VX-765 300 mg tablet TID up to Week 13.

    Reporting group title
    VX-765 600 mg - Part A
    Reporting group description
    VX-765 600 mg tablet TID up to Week 13.

    Reporting group title
    VX-765 900 mg - Part A
    Reporting group description
    VX-765 900 mg tablet TID up to Week 13.

    Reporting group title
    VX-765 1200 mg - Part A
    Reporting group description
    VX-765 1200 mg tablet TID up to Week 13.

    Reporting group title
    VX-765 - Overall Part B
    Reporting group description
    Subjects who received any dose of VX-765 TID during Part B.

    Serious adverse events
    Placebo - Part A VX-765 300 mg - Part A VX-765 600 mg - Part A VX-765 900 mg - Part A VX-765 1200 mg - Part A VX-765 - Overall Part B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    3 / 43 (6.98%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Carbon monoxide poisoning
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Transaminases increased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Complex partial seizures
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Placebo - Part A VX-765 300 mg - Part A VX-765 600 mg - Part A VX-765 900 mg - Part A VX-765 1200 mg - Part A VX-765 - Overall Part B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 12 (83.33%)
    5 / 10 (50.00%)
    8 / 11 (72.73%)
    6 / 11 (54.55%)
    8 / 11 (72.73%)
    35 / 43 (81.40%)
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Haematoma
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Angiomyolipoma
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Drug Hypersensitivity
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    1
    1
    0
    0
    2
    Influenza like illness
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    Asthenia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Irritability
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    0
    0
    0
    1
    Affect Lability
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Dysphemia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Stress
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Anxiety
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    4 / 43 (9.30%)
         occurrences all number
    0
    0
    0
    0
    0
    5
    Confusional state
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hallucination
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Sleep disorder
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    1 / 11 (9.09%)
    3 / 43 (6.98%)
         occurrences all number
    1
    0
    0
    2
    1
    9
    Procedural Pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    1 / 11 (9.09%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    Fall
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Hand fracture
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Cartilage injury
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Lip injury
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Laceration
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Muscle Strain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Thermal Burn
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Investigations
    Anticonvulsant Drug Level Increased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Blood urine present
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    3 / 43 (6.98%)
         occurrences all number
    1
    0
    0
    1
    0
    4
    Nasal congestion
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Pneumonia Aspiration
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Sinus Congestion
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Epistaxis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nasal dryness
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 12 (25.00%)
    3 / 10 (30.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    8 / 43 (18.60%)
         occurrences all number
    5
    3
    1
    0
    3
    13
    Burning Sensation
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Cerebellar Atrophy
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    Head Discomfort
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    Hyporeflexia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Sedation
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    Convulsion
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    3 / 43 (6.98%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    Paraesthesia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Migraine
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Postictal paralysis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Sensory disturbance
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Status epilepticus
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Tremor
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Disturbance in attention
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Eye disorders
    Blepharitis
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Diplopia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Eye Irritation
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vision Blurred
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blepharospasm
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypoacusis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    3 / 12 (25.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    5
    1
    0
    1
    0
    2
    Diarrhoea
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 10 (10.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    3 / 43 (6.98%)
         occurrences all number
    2
    1
    1
    0
    0
    3
    Dyspepsia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    Food poisoning
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Haemorrhoids
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 10 (0.00%)
    2 / 11 (18.18%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    Nausea
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 11 (9.09%)
    1 / 11 (9.09%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    1
    2
    1
    0
    Toothache
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    2 / 11 (18.18%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    0
    Abdominal Pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Cheilitis
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dry Mouth
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Frequent Bowel Movements
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hypoaesthesia Oral
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Tongue Disorder
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Hepatic Function Abnormal
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Dermatitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Increased Tendency to Bruise
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pruritus Generalised
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Pain in Extremity
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    1 / 11 (9.09%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    2
    1
    1
    0
    Musculoskeletal Pain
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Myalgia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Muscle spasms
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Arthralgia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Back pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Increased appetite
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    4 / 43 (9.30%)
         occurrences all number
    3
    0
    2
    0
    1
    5
    Sinusitis
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    Acute Tonsillitis
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Genital herpes
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Lower Respiratory Tract Infection
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Oral Herpes
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Orchitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pharyngitis Streptococcal
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Tooth Abscess
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vulvovaginal Mycotic Infection
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Ear lobe infection
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Oropharyngeal candidiasis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastroenteritis viral
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    0 / 11 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
    1 / 11 (9.09%)
    2 / 11 (18.18%)
    3 / 43 (6.98%)
         occurrences all number
    1
    0
    1
    1
    2
    3

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jan 2012
    Added an interim analysis for the evaluation of efficacy endpoints to assist with the planning of clinical development activities with VX-765.
    13 Apr 2012
    Added “Part A” and “Part B”. “Part A” included the randomized, double-blind, placebo-controlled, parallel-group, dose-ranging part of the study and “Part B” included the OLE.
    23 Apr 2012
    Clarified the Day 92 assessments in Part B.

    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.
    Decimal point consistency could not be maintained as EudraCT system does not recognize the trailing zero after decimal point.
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