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    Clinical Trial Results:
    A Randomized, Comparative, Double-Blind, Parallel-Group, Multicenter, Monotherapy, Study Of Pregabalin (Lyrica) And Lamotrigine(Lamicital) In Patients With Newly Diagnosed Partial Seizures

    Summary
    EudraCT number
    		 2005-004023-19
    Trial protocol
    		 GB   SE   PT   ES   BE   IE   CZ   LT   DE   SK   IT   HU   FI   EE   BG   LV  
    Global end of trial date
    01 Apr 2010

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 May 2016
    First version publication date
    25 Jul 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    A0081046
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00280059
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Sep 2010
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Apr 2010
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    1. To evaluate the efficacy of pregabalin as a monotherapy treatment compared with lamotrigine, both administered twice a day (BID), in subjects with newly diagnosed partial seizures. 2. To assess the safety and tolerability of pregabalin monotherapy compared with lamotrigine.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Aug 2006
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Norway: 3
    Country: Number of subjects enrolled
    Portugal: 27
    Country: Number of subjects enrolled
    Slovakia: 21
    Country: Number of subjects enrolled
    Spain: 21
    Country: Number of subjects enrolled
    Sweden: 15
    Country: Number of subjects enrolled
    United Kingdom: 12
    Country: Number of subjects enrolled
    Belgium: 23
    Country: Number of subjects enrolled
    Bulgaria: 29
    Country: Number of subjects enrolled
    Czech Republic: 41
    Country: Number of subjects enrolled
    Estonia: 7
    Country: Number of subjects enrolled
    Finland: 8
    Country: Number of subjects enrolled
    France: 10
    Country: Number of subjects enrolled
    Germany: 17
    Country: Number of subjects enrolled
    Hungary: 8
    Country: Number of subjects enrolled
    Ireland: 1
    Country: Number of subjects enrolled
    Italy: 16
    Country: Number of subjects enrolled
    Lithuania: 81
    Country: Number of subjects enrolled
    Thailand: 15
    Country: Number of subjects enrolled
    China: 50
    Country: Number of subjects enrolled
    Colombia: 20
    Country: Number of subjects enrolled
    Hong Kong: 33
    Country: Number of subjects enrolled
    India: 51
    Country: Number of subjects enrolled
    Korea, Republic of: 82
    Country: Number of subjects enrolled
    Mexico: 26
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Romania: 4
    Country: Number of subjects enrolled
    Singapore: 2
    Country: Number of subjects enrolled
    Taiwan: 34
    Worldwide total number of subjects
    660
    EEA total number of subjects
    347
    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)
    18
    Adults (18-64 years)
    609
    From 65 to 84 years
    32
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Study was initiated on 07 August 2006 and completed on 01 April 2010. Subjects were enrolled from 28 countries.

    Period 1
    Period 1 title
    Efficacy Assessment Phase
    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
    		 Pregabalin- Efficacy Phase
    Arm description
    		 Pregabalin administered orally.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pregabalin
    Investigational medicinal product code
    Other name
    Lyrica
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Pregabalin 150, 300, 450 or 600 milligrams per day (mg/day) twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.

    Arm title
    		 Lamotrigine- Efficacy Phase
    Arm description
    		 Lamotrigine administered orally.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Lamotrigine
    Investigational medicinal product code
    Other name
    Lamictal
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Lamotrigine 100, 200, 400, or 500 mg/day BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.

    Number of subjects in period 1
    		Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Started
    330
    330
    Completed
    236
    250
    Not completed
    94
    80
         Consent withdrawn by subject
    26
    25
         Adverse Event
    33
    31
         Death
    2
    -
         Laboratory abnormaility
    1
    -
         Unspecified
    7
    8
         Lost to follow-up
    6
    13
         Lack of efficacy
    19
    3
    Period 2
    Period 2 title
    Extension Phase
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Pregabalin- Extension Phase
    Arm description
    		 Pregabalin administered orally.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pregabalin
    Investigational medicinal product code
    Other name
    Lyrica
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.

    Arm title
    		 Lamotrigine- Extension Phase
    Arm description
    		 Lamotrigine administered orally.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Lamotrigine
    Investigational medicinal product code
    Other name
    Lamictal
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Lamotrigine 100, 200, 400, or 500 mg/day BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.

    Number of subjects in period 2 [1]
    		Pregabalin- Extension Phase Lamotrigine- Extension Phase
    Started
    194
    215
    Completed
    145
    177
    Not completed
    49
    38
         Unspecified
    49
    38
    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: Since "Extension Phase" (Period 2) was an optional phase, the number of subjects who entered it was less than the number who completed the "Efficacy Assessment Phase" (Period 1).

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pregabalin- Efficacy Phase
    Reporting group description
    		 Pregabalin administered orally.

    Reporting group title
    Lamotrigine- Efficacy Phase
    Reporting group description
    		 Lamotrigine administered orally.

    Reporting group values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase Total
    Number of subjects
    		 330 330 660
    Age categorical
    Units: Subjects
        < 18 years
    		 9 9 18
        Between 18 and 44 years
    		 228 228 456
        Between 45 and 64 years
    		 79 74 153
        >= 65 years
    		 14 19 33
    Gender categorical
    Units: Subjects
        Female
    		 165 146 311
        Male
    		 165 184 349

    End points

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    End points reporting groups
    Reporting group title
    Pregabalin- Efficacy Phase
    Reporting group description
    		 Pregabalin administered orally.

    Reporting group title
    Lamotrigine- Efficacy Phase
    Reporting group description
    		 Lamotrigine administered orally.
    Reporting group title
    Pregabalin- Extension Phase
    Reporting group description
    		 Pregabalin administered orally.

    Reporting group title
    Lamotrigine- Extension Phase
    Reporting group description
    		 Lamotrigine administered orally.

    Subject analysis set title
    Pregabalin 150 mg/Day
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pregabalin 150 mg/day administered twice daily (BID).

    Subject analysis set title
    Pregabalin 300 mg/Day
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pregabalin 300 mg/day administered BID.

    Subject analysis set title
    Pregabalin 450 mg/Day
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pregabalin 450 mg/day administered BID.

    Subject analysis set title
    Pregabalin 600 mg/Day
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pregabalin 600 mg/day administered BID.

    Subject analysis set title
    Lamotrigine 100 mg/Day
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Lamotrigine 100 mg/day administered BID.

    Subject analysis set title
    Lamotrigine 200 mg/Day
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Lamotrigine 200 mg/day administered BID.

    Subject analysis set title
    Lamotrigine 400 mg/Day
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Lamotrigine 400 mg/day administered BID.

    Subject analysis set title
    Lamotrigine 500 mg/Day
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Lamotrigine 500 mg/day administered BID.

    Primary: Percentage of Seizure-free Subjects (Responders) During Efficacy Assessment Phase

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    End point title
    		 Percentage of Seizure-free Subjects (Responders) During Efficacy Assessment Phase
    End point description
    Responders equal to (=) subjects who achieved any 6 consecutive months (greater than [>] 182 days) of seizure-freedom (absence of partial seizures, generalized seizures and unclassified epileptic seizures) during the 52 week efficacy assessment phase. Full analysis set (FAS) (intent to treat population): randomized subjects who took at least 1 dose of study medication. Analysis excludes subjects who did not enter maintenance phase of study.
    End point type
    Primary
    End point timeframe
    Week 5 up to Week 56
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    314 [1]
    308 [2]
    Units: percentage of subjects
        number (not applicable)
    51.6
    67.9
    Notes
    [1] - N = number of subjects who had at least 1 dose of study treatment and seizure efficacy data.
    [2] - N = number of subjects who had at least 1 dose of study treatment and seizure efficacy data.
    Statistical analysis title
    		 Analysis of Percentage (%) of Responders
    Statistical analysis description
    Analysis of binary response variable for 6 consecutive months seizure freedom analyzed by comparing proportions of favorable responders between the 2 treatment groups after stratifying by clusters and correcting for skewness(Gart and Nam,1990). Percentage obtained by multiplying proportion by 100. 95% confidence interval(CI) for true difference in proportions, as well as 1-sided test at α=0.025;CI adjusted for centers clustered within a geographical region with upper and lower confidence limits.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    622
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    		 Gart and Nam: correction of skewness
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.24
         upper limit
    		 -0.09
    Notes
    [3] - Non-inferiority margin for the proportion of seizure free subjects set at 10%; non-inferiority declared if the lower bound of the 95% confidence interval (CI) of the difference in seizure-free proportion between pregabalin and lamotrigine was no more than 10% in favor of lamotrigine, but 0 was contained within the lower bound of the CI. Interpretation of superiority required lower bound of CI did not contain 0 in favor of pregabalin.

    Secondary: Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures

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    End point title
    		 Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures
    End point description
    Time in days, from first day of study medication to the first 6 months of seizure freedom after Day 28. Subjects who did not achieve 6 months seizure freedom after Day 28 were censored from analysis. FAS. N = number of subjects who entered maintenance phase of study and had seizure efficacy data.
    End point type
    Secondary
    End point timeframe
    Week 4 up to Week 56
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    314
    308
    Units: days
        median (confidence interval 95%)
    254 (199 to 295)
    183 (183 to 209)
    Statistical analysis title
    		 Analysis of Time to 6 Months of Seizure-freedom
    Statistical analysis description
    Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio > 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    622
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0034 [4]
    Method
    		 Regression, Cox
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 0.9
    Notes
    [4] - Nominal value for 2-sided test calculated using Cox proportional hazards model, adjusted for geographic regions.

    Secondary: Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase)

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    End point title
    		 Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase)
    End point description
    Number of subjects who exited the study due to adverse events during the double-blind treatment period. Time in days, from first day of study treatment to day of exit from the study due to an adverse event (that is [ie], last day on study medication) during the double blind treatment period (including dose escalation phase) was inestimable. Observations with other reasons for exiting or subjects who did not exit the study were right censored as of the last day on study medication. FAS. Time to exit due to adverse events was inestimable as survival estimate at end of maintenance phase was below 0.500.
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 56
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    330 [5]
    330 [6]
    Units: subjects
    33
    31
    Notes
    [5] - N = number of subjects who entered maintenance phase of study and had seizure efficacy data.
    [6] - N = number of subjects who entered maintenance phase of study and had seizure efficacy data.
    Statistical analysis title
    		 Analysis of Exit due to Adverse Events
    Statistical analysis description
    Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio less than (<) 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    660
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8047 [7]
    Method
    		 Cox proportional hazards model
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 1.74
    Notes
    [7] - Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.

    Secondary: Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase)

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    End point title
    		 Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase)
    End point description
    Number of subjects who exited the study for any reason during the double blind treatment phase. Time in days, from first day of study treatment to day of exit from the study due to any reason (ie, last day on study medication) was inestimable. Subjects who did not exit the study were right censored as of the last day on study medication. FAS. Time to exit for any reason during the double-blind treatment phase was inestimable as the survival estimate at the end of the maintenance phase was below 0.500.
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 56
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    330 [8]
    330 [9]
    Units: subjects
    94
    80
    Notes
    [8] - N = number of subjects who had at least 1 dose of study treatment and seizure efficacy data.
    [9] - N = number of subjects who had at least 1 dose of study treatment and seizure efficacy data.
    Statistical analysis title
    		 Analysis of Exit for any Reason
    Statistical analysis description
    Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
    Comparison groups
    Lamotrigine- Efficacy Phase v Pregabalin- Efficacy Phase
    Number of subjects included in analysis
    660
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2537 [10]
    Method
    		 Cox proportional hazards model
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.6
    Notes
    [10] - Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.

    Secondary: Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase

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    End point title
    		 Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase
    End point description
    Number of subjects who exited the study due to lack of efficacy after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit due to lack of efficacy after Day 28 of the escalation phase (ie, last day on study medication) was inestimable. Subjects who did not exit or exited for a different reason were right censored as of the last day on study medication. FAS.Time to exit due to lack of efficacy after 4-week dose escalation phase was inestimable as survival estimate at end of maintenance phase was below 0.500.
    End point type
    Secondary
    End point timeframe
    Week 4 up to Week 56
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    329 [11]
    330
    Units: subjects
    78
    58
    Notes
    [11] - N = number of subjects who entered maintenance phase of study and had seizure efficacy data.
    Statistical analysis title
    		 Analysis of Exit due to Efficacy
    Statistical analysis description
    Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    659
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0025 [12]
    Method
    		 Cox proportional hazards model
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    6.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.93
         upper limit
    		 22.04
    Notes
    [12] - Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.

    Secondary: Exit Due to Any Reason After 4-week Dose Escalation Phase

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    End point title
    		 Exit Due to Any Reason After 4-week Dose Escalation Phase
    End point description
    Number of subjects who exited the study due to any reason after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit after Day 28 of the study due to any reason (ie, last day on study medication) was inestimable. Subjects who did not exit or did not reach this phase were right censored as of the last day on study medication. FAS. Time to exit for any reason after the 4-week dose escalation phase was inestimable as the survival estimate at the end of the maintenance phase was below 0.500.
    End point type
    Secondary
    End point timeframe
    Week 4 up to Week 56
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    329 [13]
    300 [14]
    Units: subjects
    78
    58
    Notes
    [13] - N = number of subjects who entered maintenance phase of study and had seizure efficacy data.
    [14] - N = number of subjects who entered maintenance phase of study and had seizure efficacy data.
    Statistical analysis title
    		 Exit After 4-week Dose Escalation Phase
    Statistical analysis description
    Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    629
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0744 [15]
    Method
    		 Cox proportional hazards model
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 1.91
    Notes
    [15] - Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.

    Secondary: Time to First Seizure After the 4-Week Dose Escalation Phase

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    End point title
    		 Time to First Seizure After the 4-Week Dose Escalation Phase
    End point description
    Time in days, from first day of study treatment to the day of first seizure after Day 28 of the escalation phase (ie, last day on study medication). Subjects who did not reach this phase or who did not have a seizure after Day 28 were right censored from the analysis as of the last day on study medication. FAS.
    End point type
    Secondary
    End point timeframe
    Week 4 up to Week 56
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    329 [16]
    300 [17]
    Units: days
        median (confidence interval 95%)
    85 (59 to 120)
    211 (145 to 342)
    Notes
    [16] - N = number of subjects who entered maintenance phase of study and had seizure efficacy data.
    [17] - N = number of subjects who entered maintenance phase of study and had seizure efficacy data.
    Statistical analysis title
    		 Analysis of Time to First Seizure
    Statistical analysis description
    Risk ratio=hazard ratio estimated from the Cox proportional hazards model for assessing a treatment difference, risk ratio < 1 is in favor of pregabalin. The 95% confidence interval is for the true risk ratio.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    629
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0003 [18]
    Method
    		 Cox proportional hazards model
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.19
         upper limit
    		 1.8
    Notes
    [18] - Nominal value for 2-sided test calculated using Cox proportional hazards model adjusted for geographical cluster.

    Secondary: Median Monthy Seizure Frequency: All Partial Seizures

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    End point title
    		 Median Monthy Seizure Frequency: All Partial Seizures
    End point description
    All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation). FAS.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 60
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    329 [19]
    330
    Units: seizures/28 days
    median (standard deviation)
        Dose-escalation phase (Weeks 1 - 4) (n=329, 330)
    0 ( 9.348 )
    0 ( 27.118 )
        Month 1 (n=314, 308)
    0 ( 6.139 )
    0 ( 31.453 )
        Month 2 (n=300, 295)
    0 ( 3.382 )
    0 ( 28.839 )
        Month 3 (n=287, 288)
    0 ( 2.568 )
    0 ( 32.783 )
        Month 4 (n=279, 278)
    0 ( 2.313 )
    0 ( 16.046 )
        Month 5 (n=274, 276)
    0 ( 2.27 )
    0 ( 15.254 )
        Month 6 (n=266, 272)
    0 ( 2.702 )
    0 ( 15.126 )
        Month 7 (n=260, 270)
    0 ( 2.839 )
    0 ( 16.855 )
        Month 8 (n=256, 266)
    0 ( 3.247 )
    0 ( 19.111 )
        Month 9 (n=253, 262)
    0 ( 2.538 )
    0 ( 17.204 )
        Month 10 (n=250, 257)
    0 ( 4.935 )
    0 ( 16.905 )
        Month 11 (n=242, 254)
    0 ( 3.082 )
    0 ( 19.268 )
        Month 12 (n=238, 252)
    0 ( 7.018 )
    0 ( 19.59 )
        Month 13 (n=210, 227)
    0 ( 3.247 )
    0 ( 19.462 )
        Taper (Week 57 to Week 60) (n=71, 45)
    0 ( 6.418 )
    0 ( 97.196 )
    Notes
    [19] - N = number of subjects with analyzable data.
    No statistical analyses for this end point

    Secondary: Mean Monthy Seizure Frequency: All Partial Seizures

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    End point title
    		 Mean Monthy Seizure Frequency: All Partial Seizures
    End point description
    All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation). FAS.n = number of subjects with analyzable data at observation.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 60
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    329 [20]
    330
    Units: seizures/28 days
    arithmetic mean (standard deviation)
        Dose escalation phase (n=329, 330)
    2.56 ( 9.348 )
    5.08 ( 27.118 )
        Month 1 (n=314, 308)
    2.23 ( 6.139 )
    4.21 ( 31.453 )
        Month 2 (n=300, 295)
    1.18 ( 3.382 )
    3.21 ( 28.839 )
        Month 3 (n=287, 288)
    0.94 ( 2.568 )
    3.54 ( 32.783 )
        Month 4 (n=279, 278)
    0.89 ( 2.313 )
    1.67 ( 16.046 )
        Month 5 (n=274, 276)
    0.78 ( 2.27 )
    1.58 ( 15.254 )
        Month 6 (n=266, 272)
    0.82 ( 2.702 )
    1.41 ( 15.126 )
        Month 7 (n=260, 270)
    0.78 ( 2.839 )
    1.5 ( 16.855 )
        Month 8 (n=256, 266)
    0.77 ( 3.247 )
    1.36 ( 19.111 )
        Month 9 (n=253, 262)
    0.71 ( 2.538 )
    1.38 ( 17.204 )
        Month 10 (n=250, 257)
    1.05 ( 4.935 )
    1.33 ( 16.905 )
        Month 11 (n=242, 254)
    0.79 ( 3.082 )
    1.41 ( 19.268 )
        Month 12 (n=238, 252)
    0.94 ( 7.018 )
    1.67 ( 19.59 )
        Month 13 (n=210, 227)
    0.65 ( 3.247 )
    2.11 ( 19.462 )
        Taper (n=71, 45)
    2.13 ( 6.418 )
    19.97 ( 97.196 )
    Notes
    [20] - N = number of subjects with analyzable data.
    No statistical analyses for this end point

    Secondary: Median Monthy Seizure Frequency: All Seizures

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    End point title
    		 Median Monthy Seizure Frequency: All Seizures
    End point description
    Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation). FAS. n = number of subjects with analyzable data at observation.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 60
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    329 [21]
    330
    Units: seizures/28 days
    median (standard deviation)
        Dose-escalation phase (Weeks 1 - 4)(n=329, 330)
    0 ( 9.819 )
    0 ( 27.128 )
        Month 1 (n=314, 308)
    0 ( 6.164 )
    0 ( 31.452 )
        Month 2 (n=300, 295)
    0 ( 5.498 )
    0 ( 28.838 )
        Month 3 (n=287, 288)
    0 ( 2.702 )
    0 ( 32.782 )
        Month 4 (n=279, 278)
    0 ( 3.223 )
    0 ( 16.046 )
        Month 5 (n=274, 276)
    0 ( 2.458 )
    0 ( 15.254 )
        Month 6 (n=266, 272)
    0 ( 2.853 )
    0 ( 15.126 )
        Month 7 (n=260, 270)
    0 ( 2.898 )
    0 ( 16.855 )
        Month 8 (n=256, 266)
    0 ( 3.304 )
    0 ( 19.11 )
        Month 9 (n=253, 262)
    0 ( 2.636 )
    0 ( 17.204 )
        Month 10 (n=250, 257)
    0 ( 4.934 )
    0 ( 16.905 )
        Month 11 (n=242, 254)
    0 ( 3.224 )
    0 ( 19.268 )
        Month 12 (n=238, 252)
    0 ( 7.019 )
    0 ( 19.59 )
        Month 13 (n=210, 227)
    0 ( 3.247 )
    0 ( 19.462 )
        Taper (Week 57 to Week 60) (n=71, 45)
    0 ( 6.418 )
    0 ( 97.196 )
    Notes
    [21] - N = number of subjects with analyzable data.
    No statistical analyses for this end point

    Secondary: Mean Monthy Seizure Frequency: All Seizures

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    End point title
    		 Mean Monthy Seizure Frequency: All Seizures
    End point description
    Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation). FAS. n = number of subjects with analyzable data at observation.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 60
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    329 [22]
    330
    Units: seizures/28 days
    arithmetic mean (standard deviation)
        Dose-escalation phase (n=329, 330)
    2.74 ( 9.819 )
    5.1 ( 27.128 )
        Month 1 (n=314, 308)
    2.31 ( 6.164 )
    4.24 ( 31.452 )
        Month 2 (n=300, 295)
    1.53 ( 5.498 )
    3.22 ( 28.838 )
        Month 3 (n=287, 288)
    1.02 ( 2.702 )
    3.57 ( 32.782 )
        Month 4 (n=279, 278)
    1.06 ( 3.223 )
    1.68 ( 16.046 )
        Month 5 (n=274, 276)
    0.87 ( 2.458 )
    1.59 ( 15.254 )
        Month 6 (n=266, 272)
    0.89 ( 2.853 )
    1.41 ( 15.126 )
        Month 7 (n=260, 270)
    0.83 ( 2.898 )
    1.5 ( 16.855 )
        Month 8 (n=256, 266)
    0.82 ( 3.304 )
    1.37 ( 19.11 )
        Month 9 (n=253, 262)
    0.78 ( 2.636 )
    1.38 ( 17.204 )
        Month 10 (n=250, 257)
    1.06 ( 4.934 )
    1.33 ( 16.905 )
        Month 11 (n=242, 254)
    0.81 ( 3.224 )
    1.41 ( 19.268 )
        Month 12 (n=238, 252)
    0.96 ( 7.019 )
    1.67 ( 19.59 )
        Month 13 (n=210, 227)
    0.65 ( 3.247 )
    2.12 ( 19.462 )
        Taper (n=71, 45)
    2.13 ( 6.418 )
    19.97 ( 97.196 )
    Notes
    [22] - N = number of subjects with analyzable data.
    No statistical analyses for this end point

    Secondary: Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures

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    End point title
    		 Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures
    End point description
    All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = subject who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom. FAS. n = number of responders with analyzable data at observation. Here "99999" in the standard deviation (SD) and median signifies not available (NA). SD was not calculated as either no subject (n=0) or 1 subject (n=1) was evaluated at these time points. Median was not calculated at month 9 for 'Pregabalin' arm as no responders with analyzable data were found.
    End point type
    Secondary
    End point timeframe
    Month 1 through Month 9 (after 6 months seizure freedom achieved)
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    162 [23]
    208 [24]
    Units: seizures/28 days
    median (standard deviation)
        Month 1 (n=162, 208)
    0 ( 1 )
    0 ( 0.226 )
        Month 2 (n=155, 194)
    0 ( 1.783 )
    0 ( 0.226 )
        Month 3 (n=147, 184)
    0 ( 0.384 )
    0 ( 0.439 )
        Month 4 (n=139, 173)
    0 ( 0.329 )
    0 ( 0.211 )
        Month 5 (n=127, 158)
    0 ( 0.926 )
    0 ( 0.823 )
        Month 6 (n=122, 152)
    0 ( 0.156 )
    0 ( 0.213 )
        Month 7 (n=105, 136)
    0 ( 0 )
    0 ( 2.843 )
        Month 8 (n=1, 5)
    0 ( 99999 )
    0 ( 0 )
        Month 9 (n=0, 1)
    99999 ( 99999 )
    6 ( 99999 )
    Notes
    [23] - N = number of responders.
    [24] - N = number of responders.
    No statistical analyses for this end point

    Secondary: Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures

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    End point title
    		 Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures
    End point description
    All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = subject who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom. FAS. n = number of responders with analyzable data at observation. Here "99999" in SD and arithmetic mean signifies not available (NA). SD was not calculated as either no subject (n=0) or only 1 subject (n=1) was evaluated at these time points. Mean was not calculated at month 9 for 'Pregabalin' arm as no responders with analyzable data were found.
    End point type
    Secondary
    End point timeframe
    Month 1 through Month 9 (after 6 months seizure freedom achieved)
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    162 [25]
    208 [26]
    Units: 28-day seizure rate
    arithmetic mean (standard deviation)
        Month 1 (n=162, 208)
    0.19 ( 1 )
    0.04 ( 0.226 )
        Month 2 (n=155, 194)
    0.28 ( 1.783 )
    0.03 ( 0.226 )
        Month 3 (n=147, 184)
    0.05 ( 0.384 )
    0.07 ( 0.439 )
        Month 4 (n=139, 173)
    0.09 ( 0.329 )
    0.05 ( 0.211 )
        Month 5 (n=127, 158)
    0.15 ( 0.926 )
    0.1 ( 0.823 )
        Month 6 (n=122, 152)
    0.02 ( 0.156 )
    0.03 ( 0.213 )
        Month 7 (n=105, 136)
    0 ( 0 )
    0.28 ( 2.843 )
        Month 8 (n=1, 5)
    0 ( 99999 )
    0 ( 0 )
        Month 9 (n=0, 1)
    99999 ( 99999 )
    6 ( 99999 )
    Notes
    [25] - N = number of responders.
    [26] - N = number of responders.
    No statistical analyses for this end point

    Secondary: Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures

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    End point title
    		 Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures
    End point description
    Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = subject who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom. FAS. n = number of responders with analyzable data at observation. Here "99999" in the SD and median signifies not available (NA). SD was not calculated as either no subject (n=0) or only 1 subject (n=1) was evaluated at these time points. Median was not calculated at month 9 for 'Pregabalin' arm as no responders with analyzable data were found.
    End point type
    Secondary
    End point timeframe
    Month 1 through Month 9 (after 6 months seizure freedom achieved)
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    162 [27]
    208 [28]
    Units: seizures/28 days
    median (standard deviation)
        Month 1 (n=162, 208)
    0 ( 1 )
    0 ( 0.236 )
        Month 2 (n=155, 194)
    0 ( 1.783 )
    0 ( 0.226 )
        Month 3 (n=147, 184)
    0 ( 0.4 )
    0 ( 0.439 )
        Month 4 (n=139, 173)
    0 ( 0.359 )
    0 ( 0.211 )
        Month 5 (n=127, 158)
    0 ( 0.971 )
    0 ( 0.823 )
        Month 6 (n=122, 152)
    0 ( 0.156 )
    0 ( 0.213 )
        Month 7 (n=105, 136)
    0 ( 0 )
    0 ( 2.844 )
        Month 8 (n=1, 5)
    0 ( 99999 )
    0 ( 0 )
        Month 9 (n=0, 1)
    99999 ( 99999 )
    6 ( 99999 )
    Notes
    [27] - N = number of responders.
    [28] - N = number of responders.
    No statistical analyses for this end point

    Secondary: Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures

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    End point title
    		 Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures
    End point description
    Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = subject who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom. FAS. n = number of responders with analyzable data at observation. Here "99999" in the (SD) and arithmetic mean signifies not available (NA). SD was not calculated as either no subject (n=0) or only 1 subject (n=1) was evaluated at these time points. Mean was not calculated at month 9 for 'Pregabalin' arm as no responders with analyzable data were found.
    End point type
    Secondary
    End point timeframe
    Month 1 through Month 9 (after 6 months seizure freedom achieved)
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    162 [29]
    208 [30]
    Units: 28-day seizure rate
    arithmetic mean (standard deviation)
        Month 1 (n=162, 208)
    0.19 ( 1 )
    0.05 ( 0.236 )
        Month 2 (n=155, 194)
    0.28 ( 1.783 )
    0.03 ( 0.226 )
        Month 3 (n=147, 184)
    0.07 ( 0.4 )
    0.07 ( 0.439 )
        Month 4 (n=139, 173)
    0.09 ( 0.359 )
    0.05 ( 0.211 )
        Month 5 (n=127, 158)
    0.18 ( 0.971 )
    0.1 ( 0.823 )
        Month 6 (n=122, 152)
    0.02 ( 0.156 )
    0.03 ( 0.213 )
        Month 7 (n=105, 136)
    0 ( 0 )
    0.29 ( 2.844 )
        Month 8 (n=1, 5)
    0 ( 99999 )
    0 ( 0 )
        Month 9 (n=0, 1)
    99999 ( 99999 )
    6 ( 99999 )
    Notes
    [29] - N = number of responders.
    [30] - N = number of responders.
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group

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    End point title
    		 Percentage of Subjects Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group
    End point description
    Responder = subject who achieved at least 6-months of seizure freedom (all seizures) after Week 4, and up to Week 56. Dose Level defined as last total-daily-dose received after Week 4, and up to Week 56. FAS.
    End point type
    Secondary
    End point timeframe
    Week 5 up to Week 56
    End point values
    		 Pregabalin 150 mg/Day Pregabalin 300 mg/Day Pregabalin 450 mg/Day Pregabalin 600 mg/Day Lamotrigine 100 mg/Day Lamotrigine 200 mg/Day Lamotrigine 400 mg/Day Lamotrigine 500 mg/Day
    Number of subjects analysed
    149 [31]
    67 [32]
    49 [33]
    46 [34]
    164 [35]
    84 [36]
    34 [37]
    18 [38]
    Units: percentage of subjects
        number (not applicable)
    70.5
    59.7
    20.4
    13
    80.5
    67.9
    38.2
    16.7
    Notes
    [31] - N = number of subjects with analyzable data.
    [32] - N = number of subjects with analyzable data.
    [33] - N = number of subjects with analyzable data.
    [34] - N = number of subjects with analyzable data.
    [35] - N = number of subjects with analyzable data.
    [36] - N = number of subjects with analyzable data.
    [37] - N = number of subjects with analyzable data.
    [38] - N = number of subjects with analyzable data.
    No statistical analyses for this end point

    Secondary: Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS)

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    End point title
    		 Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (HADS)
    End point description
    Subject rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items; range: 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of symptoms. Scores relative to start of randomized treatment. FAS.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 56
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    237 [39]
    238 [40]
    Units: scores on scale
    least squares mean (standard error)
        Anxiety
    -0.3 ( 0.25 )
    -1.1 ( 0.25 )
        Depression
    -0.1 ( 0.23 )
    -0.7 ( 0.23 )
    Notes
    [39] - N = number of subjects with a HADS measurement at baseline and Week 56.
    [40] - N = number of subjects with a HADS measurement at baseline and Week 56.
    Statistical analysis title
    		 Analysis of Change in Anxiety: HADS
    Statistical analysis description
    Anxiety; model includes treatment and geographical cluster as fixed effects and respective baseline scores as a continuous covariate.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    475
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0025
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 1.4
    Statistical analysis title
    		 Analysis of Change in Depression: HADS
    Statistical analysis description
    Depression; model includes treatment and geographical cluster as fixed effects and respective baseline scores as a continuous covariate.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    475
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0186
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 1.1

    Secondary: Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale

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    End point title
    		 Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale
    End point description
    MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Optimal Sleep subscale is derived from sleep quantity average hours of sleep each night during the past week. Number of subjects with response Optimal if sleep quantity was 7 or 8 hours of sleep per night, and Non-optimal if average sleep was less than or greater than 7 to 8 hours per night. Analysis assesses the MOS-Sleep scale relative to the start of randomized treatment. FAS.
    End point type
    Secondary
    End point timeframe
    Week 8, Week 32, and Week 56
    End point values
    		 Pregabalin- Efficacy Phase Lamotrigine- Efficacy Phase
    Number of subjects analysed
    330
    330
    Units: subjects
        Week 8: Optimal sleep
    195
    173
        Week 8: Non-optimal sleep
    103
    126
        Week 32: Optimal sleep
    167
    155
        Week 32: Non-optimal sleep
    97
    103
        Week 56: Optimal sleep
    152
    145
        Week 56: Non-optimal sleep
    82
    90
    Statistical analysis title
    		 Analysis of MOS-SS at Week 8
    Statistical analysis description
    Week 8: dichotomized sleep assessment analyzed using a logistic regression model for repeated measures with fixed effects for treatment, geographical region, the average hours per night of sleep at baseline as a continuous covariate, time, and treatment-by-time interaction. The within subject covariance structure assumes an auto-regressive of order one covariance structure.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    660
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0683
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.93
    Statistical analysis title
    		 Analysis of MOS-SS at Week 32
    Statistical analysis description
    Week 32: dichotomized sleep assessment analyzed using a logistic regression model for repeated measures with fixed effects for treatment, geographical region, the average hours per night of sleep at baseline as a continuous covariate, time, and treatment-by-time interaction. The within subject covariance structure assumes an auto-regressive of order one covariance structure.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    660
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5096
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.66
    Statistical analysis title
    		 Analysis of MOS-SS at Week 56
    Statistical analysis description
    Week 56 (termination): dichotomized sleep assessment analyzed using a logistic regression model for repeated measures with fixed effects for treatment, geographical region, the average hours per night of sleep at baseline as a continuous covariate, time, and treatment-by-time interaction. The within subject covariance structure assumes an auto-regressive of order one covariance structure.
    Comparison groups
    Pregabalin- Efficacy Phase v Lamotrigine- Efficacy Phase
    Number of subjects included in analysis
    660
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6804
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.63

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were recorded from Day 0 (randomization visit) to End of Week 56 (termination visit).
    Adverse event reporting additional description
    Same event may appear as both AE,SAE. However,what is presented are distinct events.An event may be categorized as serious in 1 subject and as nonserious in another,or 1 subject may experience both serious,nonserious event. EU BR specific AE tables were generated separately as per EU format. Latest coding dictionary has been used for EU BR tables.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Lamotrigine
    Reporting group description
    		 Lamotrigine 100, 200, 400, or 500 mg/day orally BID; individual titration based on number of seizures experienced once Level 1 (100 mg/day) was reached and maintained for 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.

    Reporting group title
    Pregabalin
    Reporting group description
    		 Pregabalin 150, 300, 450 or 600 mg/day orally twice daily (BID); individual titration based on number of seizures experienced once Level 1 (150 mg/day) was maintained for at least 7 days, and dose reductions based on intolerable adverse events. Escalation to next dose level allowed only after completing previous dose level for at least 1 week.

    Serious adverse events
    		 Lamotrigine Pregabalin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    32 / 330 (9.70%)
    44 / 330 (13.33%)
         number of deaths (all causes)
    2
    2
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Medullary thyroid cancer
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    T-cell lymphoma
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 330 (0.30%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Waldenstrom's macroglobulinaemia
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal neoplasm
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    Vasculitis
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Carpal tunnel decompression
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ostectomy
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip arthroplasty
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenectomy
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drowning
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sudden unexplained death in epilepsy
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Vulval oedema
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 330 (0.30%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord cyst
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium tremens
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychogenic seizure
         subjects affected / exposed
    1 / 330 (0.30%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Cartilage injury
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    4 / 330 (1.21%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    3 / 330 (0.91%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    2 / 330 (0.61%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 330 (0.00%)
    2 / 330 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin abrasion
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Multiple endocrine neoplasia Type 2
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial ischaemia
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug withdrawal convulsions
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 330 (0.00%)
    2 / 330 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    4 / 330 (1.21%)
    5 / 330 (1.52%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 330 (0.00%)
    2 / 330 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures with secondary generalisation
         subjects affected / exposed
    0 / 330 (0.00%)
    2 / 330 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postictal headache
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 330 (0.30%)
    10 / 330 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord disorder
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    1 / 330 (0.30%)
    4 / 330 (1.21%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wernicke's encephalopathy
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Splenomegaly
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Entropion
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trichiasis
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dyspepsia
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 330 (0.00%)
    2 / 330 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic epidermal necrolysis
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus ureteric
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Parathyroid gland enlargement
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthropathy
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle haemorrhage
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigger finger
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulvovaginitis
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 330 (0.00%)
    1 / 330 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    1 / 330 (0.30%)
    0 / 330 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Lamotrigine Pregabalin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    173 / 330 (52.42%)
    186 / 330 (56.36%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    7 / 330 (2.12%)
    4 / 330 (1.21%)
         occurrences all number
    7
    4
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    19 / 330 (5.76%)
    30 / 330 (9.09%)
         occurrences all number
    22
    37
    Pyrexia
         subjects affected / exposed
    14 / 330 (4.24%)
    6 / 330 (1.82%)
         occurrences all number
    15
    9
    Reproductive system and breast disorders
    Menorrhagia
         subjects affected / exposed [1]
    3 / 146 (2.05%)
    0 / 165 (0.00%)
         occurrences all number
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    10 / 330 (3.03%)
    2 / 330 (0.61%)
         occurrences all number
    12
    2
    Cough
         subjects affected / exposed
    9 / 330 (2.73%)
    2 / 330 (0.61%)
         occurrences all number
    13
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    10 / 330 (3.03%)
    5 / 330 (1.52%)
         occurrences all number
    14
    7
    Depression
         subjects affected / exposed
    14 / 330 (4.24%)
    10 / 330 (3.03%)
         occurrences all number
    16
    11
    Insomnia
         subjects affected / exposed
    19 / 330 (5.76%)
    15 / 330 (4.55%)
         occurrences all number
    21
    20
    Sleep disorder
         subjects affected / exposed
    7 / 330 (2.12%)
    2 / 330 (0.61%)
         occurrences all number
    14
    3
    Investigations
    Weight increased
         subjects affected / exposed
    7 / 330 (2.12%)
    22 / 330 (6.67%)
         occurrences all number
    7
    23
    Nervous system disorders
    Disturbance in attention
         subjects affected / exposed
    6 / 330 (1.82%)
    7 / 330 (2.12%)
         occurrences all number
    6
    9
    Dizziness
         subjects affected / exposed
    47 / 330 (14.24%)
    57 / 330 (17.27%)
         occurrences all number
    102
    114
    Headache
         subjects affected / exposed
    73 / 330 (22.12%)
    74 / 330 (22.42%)
         occurrences all number
    180
    166
    Memory impairment
         subjects affected / exposed
    13 / 330 (3.94%)
    8 / 330 (2.42%)
         occurrences all number
    15
    8
    Somnolence
         subjects affected / exposed
    16 / 330 (4.85%)
    29 / 330 (8.79%)
         occurrences all number
    20
    36
    Eye disorders
    Vision blurred
         subjects affected / exposed
    2 / 330 (0.61%)
    7 / 330 (2.12%)
         occurrences all number
    6
    8
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    17 / 330 (5.15%)
    12 / 330 (3.64%)
         occurrences all number
    19
    15
    Abdominal pain
         subjects affected / exposed
    9 / 330 (2.73%)
    4 / 330 (1.21%)
         occurrences all number
    14
    4
    Nausea
         subjects affected / exposed
    11 / 330 (3.33%)
    14 / 330 (4.24%)
         occurrences all number
    12
    15
    Dyspepsia
         subjects affected / exposed
    12 / 330 (3.64%)
    8 / 330 (2.42%)
         occurrences all number
    14
    10
    Diarrhoea
         subjects affected / exposed
    13 / 330 (3.94%)
    10 / 330 (3.03%)
         occurrences all number
    16
    10
    Constipation
         subjects affected / exposed
    5 / 330 (1.52%)
    9 / 330 (2.73%)
         occurrences all number
    5
    9
    Toothache
         subjects affected / exposed
    4 / 330 (1.21%)
    9 / 330 (2.73%)
         occurrences all number
    4
    9
    Vomiting
         subjects affected / exposed
    8 / 330 (2.42%)
    7 / 330 (2.12%)
         occurrences all number
    10
    7
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    9 / 330 (2.73%)
    4 / 330 (1.21%)
         occurrences all number
    12
    4
    Rash
         subjects affected / exposed
    18 / 330 (5.45%)
    12 / 330 (3.64%)
         occurrences all number
    23
    15
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    6 / 330 (1.82%)
    7 / 330 (2.12%)
         occurrences all number
    6
    8
    Back pain
         subjects affected / exposed
    10 / 330 (3.03%)
    9 / 330 (2.73%)
         occurrences all number
    10
    10
    Infections and infestations
    Influenza
         subjects affected / exposed
    12 / 330 (3.64%)
    13 / 330 (3.94%)
         occurrences all number
    15
    14
    Nasopharyngitis
         subjects affected / exposed
    21 / 330 (6.36%)
    15 / 330 (4.55%)
         occurrences all number
    33
    17
    Pharyngitis
         subjects affected / exposed
    4 / 330 (1.21%)
    7 / 330 (2.12%)
         occurrences all number
    4
    8
    Upper respiratory tract infection
         subjects affected / exposed
    23 / 330 (6.97%)
    20 / 330 (6.06%)
         occurrences all number
    38
    30
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    7 / 330 (2.12%)
    2 / 330 (0.61%)
         occurrences all number
    7
    2
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: Since menorrhagia is a gender specific event, only female population (146) is considered to be exposed to this adverse event which is less than the total number of subjects exposed.

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Feb 2006
    1. Addition of a blinded extension for completers of the double-blind efficacy phase who wished to continue on study medication. Subjects who continued on study medication in the blinded extension did not not enter the taper period. The blinded extension continued until the entire study was unblinded. A subject who withdrew from the blinded extension before the study was completed also entered the 4-week taper phase. 2. Subjects who received a single dose of a benzodiazepine as emergency treatment were allowed to enroll. 3. During the blinded extension visits concurrent medications and adverse events were documented. A urine pregnancy test was performed on women of childbearing potential. 4. Assessments of sensation (upper and lower), reflexes, cranial nerves, and muscle strength and tone were added to neurological examination. 5. Instead of a 12-lead Electrocardiogram (ECG) "with a 2-minute rhythm strip", just a 12-lead ECG was performed at Screening.
    15 Aug 2006
    1. Exposure in Utero definition was amended to include paternal exposure. 2. Follow-up was conducted to obtain pregnancy outcome information on all Exposure in Utero reports with an unknown outcome.

    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.
    Cox proportional hazards model for time to event (TTE) analyses; three summary statistics were not generated as median TTE will not exist if survival function (Kaplan-Meier product limit estimates) does not fall below 0.5 (post-hoc analysis).
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    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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