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Retigabine Efficacy and Safety Trial for Partial Onset Refractory Seizures in Epilepsy (RESTORE2)

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ClinicalTrials.gov Identifier: NCT00235755
Recruitment Status : Completed
First Posted : October 10, 2005
Results First Posted : November 7, 2011
Last Update Posted : April 21, 2017
Sponsor:
Collaborator:
Valeant Pharmaceuticals International, Inc.
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Seizures
Interventions Drug: Retigabine
Drug: Placebo
Enrollment 539
Recruitment Details  
Pre-assignment Details Participants who completed the Double-blind Phase (Titration plus Maintenance Phases) who elected to continue in the Open-Label Extension Study (OLE-S) entered the Transition Phase, for titration, if on placebo, or to maintain the blind if on retigabine. Participants who did not enter the Titration Phase entered a Taper Phase.
Arm/Group Title Placebo Retigabine 200 mg TID Retigabine 300 mg TID
Hide Arm/Group Description Matching placebo tablets of dummy strengths of 50 milligrams (mg) and 100 mg were administered orally thrice a day (TID) during the 4-week Titration Phase. Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 12-week Maintenance Phase. Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks. Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the 12-week Maintenance Phase. Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks. Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the 12-week Maintenance Phase.
Period Title: 4-Week Titration Phase
Started 179 181 179
Completed 168 162 153
Not Completed 11 19 26
Reason Not Completed
Adverse Event             6             14             20
Lost to Follow-up             0             1             1
Protocol Violation             2             2             1
Withdrawal by Subject             1             2             3
Participant Did Not Receive Study Drug             0             0             1
Randomization Occurred in Error             1             0             0
Prolonged QT Interval at Visit 3             1             0             0
Period Title: 12-Week Maintenance Phase
Started 168 162 153
Completed 152 135 122
Not Completed 16 27 31
Reason Not Completed
Adverse Event             8             12             26
Lost to Follow-up             2             3             0
Lack of Efficacy             5             0             0
Protocol Violation             0             4             2
Withdrawal by Subject             0             8             3
Abnormal Electrocardiogram Test Result             1             0             0
Arm/Group Title Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Total
Hide Arm/Group Description Matching placebo tablets of dummy strengths of 50 milligrams (mg) and 100 mg were administered orally thrice a day (TID) during the 4-week Titration Phase and the 12-week Maintenance Phase Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID Total of all reporting groups
Overall Number of Baseline Participants 179 181 178 538
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 179 participants 181 participants 178 participants 538 participants
37.7  (11.75) 37.5  (12.02) 37.7  (12.77) 37.6  (12.16)
[1]
Measure Description: Baseline characteristics are summarized for the Safety Population, comprised of all participants who were randomized and received at least one dose of study medication.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 179 participants 181 participants 178 participants 538 participants
Female
90
  50.3%
105
  58.0%
85
  47.8%
280
  52.0%
Male
89
  49.7%
76
  42.0%
93
  52.2%
258
  48.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 179 participants 181 participants 178 participants 538 participants
Caucasian 169 173 170 512
African-American (black) 2 2 1 5
Asian 3 0 2 5
Mixed Race 5 6 5 16
1.Primary Outcome
Title Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases)
Hide Description 28-day total PS (PSs [also called focal seizures] are seizures limited to a specific area of the brain) frequency in the BL period = (Number [No.] of total PSs reported in the BL period divided by the No. of days of available total PS data in the BL period) x 28 days. 28-day total PS frequency in the DB period = (No. of total PSs reported in the DB period divided by the No. of days of available total PS data in the DB period) x 28 days. Percent change = ([value in the DB period minus value at BL] divided by the BL value) x 100%. Negative valu es indicate a reduction in seizure frequency.
Time Frame Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Food and Drug Administration (ITT FDA) Population: all randomized participants (P) who received at least 1 dose of study drug. Only participants with post-BL seizure data are included in this analysis.
Arm/Group Title Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 milligrams (mg) and 100 mg were administered orally thrice a day (TID) during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Overall Number of Participants Analyzed 176 175 179
Median (Full Range)
Unit of Measure: percent change in seizure frequency
-15.9
(-100 to 1712)
-39.9
(-100 to 226)
-27.9
(-94 to 250)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Double Blind (DB) Phase (Titration Plus Maintenance), Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Non-parametric rank analysis of covariance adjusted for baseline 28-seizure frequency and stratified by baseline seizure frequency category and region
Method Non-parametric rank ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Double Blind (DB) Phase (Titration Plus Maintenance), Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments Non-parametric rank analysis of covariance adjusted for baseline 28-seizure frequency and stratified by baseline seizure frequency category and region
Method Non-parametric rank ANCOVA
Comments [Not Specified]
2.Primary Outcome
Title Number of Participants Classified as Responders and Non-responders During the Maintenance Phase
Hide Description Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the Maintenance Phase as compared to the Baseline period.
Time Frame Week 5 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT European Medicines Evaluation Agency (EMEA) Population: all randomized participants who had received at least 1 dose of study drug in the Maintenance Phase and had at least 1 seizure measurement (whether or not they had a seizure) recorded in the Maintenance Phase.
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12 week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Overall Number of Participants Analyzed 164 149 158
Measure Type: Number
Unit of Measure: participants
Responders 31 70 61
Non-responders 133 79 97
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - DB Phase (Titration Plus Maintenance), Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - DB Phase (Titration Plus Maintenance), Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants Who Were Responders and Non-responders During the DB Phase
Hide Description Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the DB Phase as compared to the Baseline period. Participants without any post-baseline data were considered non-responders.
Time Frame Week 1 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT FDA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 179 181 178
Measure Type: Number
Unit of Measure: participants
Responders 31 57 70
Non-responders 148 124 108
4.Secondary Outcome
Title Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
Hide Description 28-day total partial seizure frequency in the BL period = (No. of total partial seizures reported in the BL period divided by the No. of days of available total partial seizure data in the BL period) x 28 days. 28-day total partial seizure frequency in the Maintenance Phase = (No. of total partial seizures reported in the Maintenance Phase divided by the No. of days of available total partial seizure data in the same phase) x 28 days. Percent change = (value in the Maintenance Phase minus value at BL divided by the BL value) x 100%. Negative values indicate a reduction in seizure frequency.
Time Frame Baseline (Week -7 through Week 0), Week 5 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT EMEA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 164 158 149
Median (Full Range)
Unit of Measure: Percent change in seizure frequency
-17.4
(-100 to 1589)
-35.3
(-100 to 253)
-44.3
(-100 to 714)
5.Secondary Outcome
Title Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories
Hide Description Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a reduction of 75-100%, 50-<75%, 25-<50%, or <25%, in addition to having no reduction. This quartile cutting was specified in the study protocol. Participants without any post-baseline data are included in the "No reduction" category.
Time Frame Baseline (Week -7 through Week 0), Week 1 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT FDA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 179 181 178
Measure Type: Number
Unit of Measure: participants
75% to 100% reduction 12 16 27
50% to <75% reduction 19 41 43
25% to <50% reduction 39 38 41
>0 to <25% reduction 43 38 24
No reduction 66 48 43
6.Secondary Outcome
Title Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Hide Description Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized in decile cutting, i.e., reduction categories of 90-100%, 80-<90%, 70-<80%, 60-<70%, 50-<60%, 40-<50%, 30-<40%, 20-<30%, 10-<20%, >0-<10%, and increase categories of 0-10%, >10-20%, >20-30%, >30% (FDA endpoint). Participants without any post-baseline data were included in the category 0-10% increase category.
Time Frame Baseline (Week -7 through Week 0), Week 1 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT FDA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 179 181 178
Measure Type: Number
Unit of Measure: participants
Reduction: 90% to 100% 3 5 11
Reduction: 80% to <90% 4 8 14
Reduction: 70% to <80% 8 11 7
Reduction: 60% to <70% 7 14 21
Reduction: 50% to <60% 9 19 17
Reduction: 40% to <50% 9 13 17
Reduction: 30% to <40% 15 16 21
Reduction: 20% to <30% 24 16 9
Reduction: 10% to <20% 18 18 10
Reduction: >0% to <10% 16 13 8
Increase: 0% to 10% 20 11 11
Increase: >10% to 20% 13 9 7
Increase: >20% to 30% 8 3 1
Increase: >30% 25 25 24
7.Secondary Outcome
Title Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
Hide Description Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a >75%, a 50-75%, or a <50% reduction, in addition to having no reduction (EMEA endpoint).
Time Frame Baseline (Week -7 through Week 0), Week 5 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT EMEA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 164 158 149
Measure Type: Number
Unit of Measure: participants
>75% reduction 11 27 30
50% to 75% reduction 20 34 40
>0 to <50% reduction 83 60 49
No reduction 50 37 30
8.Secondary Outcome
Title Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase
Hide Description Participants who experienced an exacerbation from Baseline in the 28-day total partial seizure frequency were categorized as having a 0-25% or a >25% increase (EMEA endpoint). The number of participants experiencing a >0% reduction from Baseline in the 28-day total partial seizure frequency are also presented.
Time Frame Baseline (Week -7 through Week 0), Week 5 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT EMEA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 164 158 149
Measure Type: Number
Unit of Measure: participants
0% to 25% increase 28 14 11
>=25% increase 22 23 19
>0% reduction 114 121 119
9.Secondary Outcome
Title Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline
Hide Description New seizure types included those seizures which were not reported by any participant at Baseline.
Time Frame Baseline (Week -7 through Week 0), Week 1 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT FDA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 179 181 178
Measure Type: Number
Unit of Measure: participants
Partial seizures without motor signs 9 8 12
Partial evolving to secondarily generalized 6 5 9
Partial seizures with motor signs 5 6 3
Tonic-clonic seizures 0 0 3
Flurries 3 2 1
Tonic seizures 3 0 1
Complex partial seizures 1 4 4
Unclassified seizures 0 1 0
10.Secondary Outcome
Title Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
Hide Description Participants were considered to be seizure-free if they had not reported any seizures during the DB treatment period (Weeks 1-18). For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6. A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6. Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18.
Time Frame Week 1 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT FDA Population. Only participants with post-baseline seizure data were included in the analysis.
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 176 179 175
Measure Type: Number
Unit of Measure: participants
Seizure-free 2 0 7
Not seizure-free 174 179 168
11.Secondary Outcome
Title Number of Participants Who Were Seizure-free During the Maintenance Phase
Hide Description Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase.
Time Frame Week 5 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT EMEA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 164 158 149
Measure Type: Number
Unit of Measure: participants
Seizure-free 2 5 7
Not seizure-free 162 153 142
12.Secondary Outcome
Title Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)
Hide Description A seizure-free day was a day without any seizures. For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6. A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6. Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18. The percentage of seizure-free days was calculated as the total number of days without seizures in the DB period divided by the number of days in DB period x 100%.
Time Frame Week 1 through Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT FDA Population. Only participants who had post-baseline seizure data were included in the analysis.
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 176 179 175
Median (Full Range)
Unit of Measure: percentage of days
77.8
(0 to 100)
79.5
(0 to 99)
82.1
(0 to 100)
13.Secondary Outcome
Title Percentage of Seizure-free Days During the Maintenance Phase
Hide Description A seizure-free day was a day without any seizures. The percentage of seizure-free days was calculated as the total number of days without seizures in the Maintenance Phase divided by the number of days in the Maintenance Phase x 100%.
Time Frame Week 5 through Week 16
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ITT EMEA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 164 158 149
Median (Full Range)
Unit of Measure: percentage of days
78.1
(0 to 100)
81.6
(0 to 100)
84.5
(0 to 100)
14.Secondary Outcome
Title Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase
Hide Description Clinical Global Impression of Improvement (CGI-I) is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the treatment. Scores on the scale are rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time Frame Week 16/end of treatment phase
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ITT EMEA Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 164 158 149
Mean (Standard Deviation)
Unit of Measure: scores on a scale
3.2  (0.99) 2.9  (1.05) 2.9  (1.21)
15.Secondary Outcome
Title Patient Global Impression (PGI) Score at the End of the Maintenance Phase
Hide Description PGI is a participant-rated scale of improvement that was administered at the end of the Maintenance Phase in order to assess the participant's impression of his or her own improvement. PGI assessments were scored using a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time Frame Week 16/end of treatment phase
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ITT EMEA Population. Only participants with post-baseline PGI scores were included in the analysis.
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 155 149 139
Mean (Standard Deviation)
Unit of Measure: scores on a scale
3.3  (1.00) 2.9  (1.11) 3.0  (1.43)
16.Secondary Outcome
Title Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16
Hide Description The QOLIE-31-P is a 31-item questionnaire evaluating a participant's QOL perception in 7 domains: seizure worry, emotional well being, energy/fatigue, cognitive functioning, medication effects, social functioning, overall QOL. Precoded numeric values for some domains are such that a higher number reflects a more favorable health state; others are such that a higher number reflects a less favorable state. Precoded values are first converted to 0-100 point scores; higher converted scores always reflect better QOL. The overall score is derived by weighting and then summing the 7 domain scores.
Time Frame End of Baseline (Week 0), Weeks 4, 8, and 16
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Hide Analysis Population Description
Safety Population: all randomized participants who received at least 1 dose of retigabine or placebo. Only participants with QOLIE-31-P data were included in the analysis.
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 165 173 166
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline, n=165, 173, 166 53.3  (16.62) 56.0  (17.45) 52.1  (15.93)
Week 4 (Titration Phase), n=155, 155, 149) 55.4  (16.41) 57.3  (18.12) 52.7  (16.94)
Week 8 (Maintenance Phase), n=141, 146, 127 55.3  (17.05) 59.6  (17.32) 52.7  (16.47)
Week 16 (Maintenance Phase), n=143, 133, 123 54.7  (16.82) 59.1  (16.57) 53.2  (16.38)
17.Secondary Outcome
Title Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Hide Description Clinically important changes in laboratory values were to be reported as an adverse event if they met one of the following criteria: (1) intervention required; (2) change in dose of study drug required; (3) other treatment/therapy required; (4) association with other diagnoses.
Time Frame Week 1 through Week 16
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Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Placebo - Transition Phase Retigabine 200 mg TID - Transition Phase Retigabine 300 mg TID - Transition Phase
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Participants receiving placebo during the Maintenance Phase were titrated to a target dose of retigabine 300 mg TID during the 4-week Transition Phase in a double-dummy, double-blind manner using a transition kit consisting of retigabine and placebo tablets (50 mg and 100 mg). The starting dose for retigabine titration was 100 mg TID and was increased weekly by a maximum of 150 mg per day
Participants receiving retigabine 200 mg TID during the Maintenance Phase were titrated to a target dose of 300 mg TID retigabine during the 4-week Transition Phase in a double-dummy, double-blind manner using a transition kit consisting of retigabine and placebo tablets (50 mg and 100 mg). Retigabine doses were increased weekly by a maximum of 150 mg per day
Participants receiving retigabine 300 mg TID during the Maintenance Phase continued receiving retigabine 300 mg TID during the 4-week Transition Phase in a double-dummy, double-blind manner using a transition kit consisting of retigabine and placebo tablets (50 mg and 100 mg). Placebo doses were administered to maintain the blinding and were increased weekly by a maximum of 150 mg per day
Overall Number of Participants Analyzed 179 181 178 147 132 114
Measure Type: Number
Unit of Measure: participants
Protenuria 3 2 0 0 1 0
Hyperlipidemia 3 0 0 0 0 0
Hypercholesterolemia 2 4 1 0 0 1
Hematuria 2 5 2 1 0 1
18.Secondary Outcome
Title Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Hide Description A summary of the adverse events classified as renal or urinary disorders and in which at least 2% (rounded to an integer) of participants in any treatment arm reported during the study is presented.
Time Frame Week 1 through Week 16
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Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Placebo - Transition Phase Retigabine 200 mg TID - Transition Phase Retigabine 300 mg TID - Transition Phase
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Participants receiving placebo during the Maintenance Phase were titrated to a target dose of retigabine 300 mg TID during the 4-week Transition Phase in a double-dummy, double-blind manner using a transition kit consisting of retigabine and placebo tablets (50 mg and 100 mg). The starting dose for retigabine titration was 100 mg TID and was increased weekly by a maximum of 150 mg per day
Participants receiving retigabine 200 mg TID during the Maintenance Phase were titrated to a target dose of 300 mg TID retigabine during the 4-week Transition Phase in a double-dummy, double-blind manner using a transition kit consisting of retigabine and placebo tablets (50 mg and 100 mg). Retigabine doses were increased weekly by a maximum of 150 mg per day
Participants receiving retigabine 300 mg TID during the Maintenance Phase continued receiving retigabine 300 mg TID during the 4-week Transition Phase in a double-dummy, double-blind manner using a transition kit consisting of retigabine and placebo tablets (50 mg and 100 mg). Placebo doses were administered to maintain the blinding and were increased weekly by a maximum of 150 mg per day
Overall Number of Participants Analyzed 179 181 178 147 132 114
Measure Type: Number
Unit of Measure: participants
Dysuria 0 3 4 0 0 0
Urinary retention 0 1 4 0 0 0
Polyuria 4 1 2 0 0 0
Urinary hesitation 3 6 1 3 1 0
Haematuria 2 5 2 1 0 1
19.Secondary Outcome
Title Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase
Hide Description Post-void residual (PVR) urine refers to the amount of urine remaining in the bladder after normal urination. To investigate the possible effects of retigabine on bladder function, all participants underwent post-void residual bladder ultrasound at Baseline and during the Maintenance Phase. The PVR bladder ultrasound was performed by a urologist, a qualified ultrasound technician, or a qualified study nurse who was certified to do PVR bladder ultrasound. Change from Baseline in PVR residual volume was calculated as the values at Week 10 and Week 16 minus the value at Baseline.
Time Frame Baseline (Week -7 through 0), Weeks 8 and 16
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Hide Analysis Population Description
Safety Population. Only participants who remained in the study at the indicated week and who also had a PVR assessment were analyzed.
Arm/Group Title Placebo: Maintenance Phase Retigabine 200 mg TID: Maintenance Phase Retigabine 300 mg TID: Maintenance Phase
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the 12-week Maintenance Phase
Overall Number of Participants Analyzed 143 134 115
Median (Full Range)
Unit of Measure: milliliters
Week 8, n=143, 134, 121
0
(-107 to 148)
0
(-195 to 400)
0
(-162 to 165)
Week 16, n=141, 131, 115
0
(-185 to 232)
0
(-195 to 609)
0
(-262 to 173)
20.Secondary Outcome
Title Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase
Hide Description The number of participants with recorded weight gain of >=7% over their baseline weight was measured.
Time Frame Weeks 2 and 4 of Titration Phase and Weeks 6, 8, 12, and 16 of Maintenance Phase
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Hide Analysis Population Description
Safety Population. Only participants who remained in the study at the indicated week and who also had a body weight assessment were analyzed.
Arm/Group Title Placebo - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Hide Arm/Group Description:
Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 4-week Titration Phase and the 12-week Maintenance Phase
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID
Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID
Overall Number of Participants Analyzed 174 180 175
Measure Type: Number
Unit of Measure: participants
Week 2, n=174, 180, 175 0 3 3
Week 4, n=169, 172, 167 0 7 8
Week 6, n=169, 165, 152 1 8 7
Week 8, n=161, 160, 149 1 9 7
Week 12, n=159, 151, 144 6 15 13
Week 16, n=153, 139, 132 4 13 12
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) Placebo - Transition Phase Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - Transition Phase Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - Transition Phase
Hide Arm/Group Description Matching placebo tablets of dummy strengths of 50 milligrams (mg) and 100 mg were administered orally thrice a day (TID) during the 4-week Titration Phase and the 12-week Maintenance Phase Participants receiving placebo during the Maintenance Phase were titrated to a target dose of retigabine 300 mg TID during the 4-week Transition Phase in a double-dummy, double-blind manner using a transition kit consisting of retigabine and placebo tablets (50 mg and 100 mg). The starting dose for retigabine titration was 100 mg TID and was increased weekly by a maximum of 150 mg per day Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 600 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 200 mg TID Participants receiving retigabine 200 mg TID during the Maintenance Phase were titrated to a target dose of 300 mg TID retigabine during the 4-week Transition Phase in a double-dummy, double-blind manner using a transition kit consisting of retigabine and placebo tablets (50 mg and 100 mg). Retigabine doses were increased weekly by a maximum of 150 mg per day Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID Participants receiving retigabine 300 mg TID during the Maintenance Phase continued receiving retigabine 300 mg TID during the 4-week Transition Phase in a double-dummy, double-blind manner using a transition kit consisting of retigabine and placebo tablets (50 mg and 100 mg). Placebo doses were administered to maintain the blinding and were increased weekly by a maximum of 150 mg per day
All-Cause Mortality
Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) Placebo - Transition Phase Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - Transition Phase Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - Transition Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) Placebo - Transition Phase Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - Transition Phase Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - Transition Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/179 (3.91%)   2/147 (1.36%)   14/181 (7.73%)   3/132 (2.27%)   15/178 (8.43%)   3/114 (2.63%) 
Blood and lymphatic system disorders             
Neutropenia  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Ear and labyrinth disorders             
Vertigo  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Eye disorders             
Corneal erosion  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Visual disturbance  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Gastrointestinal disorders             
Diarrhoea  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Constipation  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Vomiting  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Abdominal pain  1  2/179 (1.12%)  1/147 (0.68%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Haemorrhoidal haemorrhage  1  1/179 (0.56%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Haemorrhoids  1  1/179 (0.56%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
General disorders             
Sudden unexplained death in epilepsy  1  1/179 (0.56%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Gait disturbance  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Chest pain  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Fatigue  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Hepatobiliary disorders             
Cholecystitis  1  2/179 (1.12%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Cholelithiasis  1  0/179 (0.00%)  1/147 (0.68%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Hepatic function abnormal  1  1/179 (0.56%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Infections and infestations             
Erysipelas  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Sepsis  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Urinary tract infection  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  1/132 (0.76%)  0/178 (0.00%)  0/114 (0.00%) 
Injury, poisoning and procedural complications             
Drug toxicity  1  0/179 (0.00%)  0/147 (0.00%)  2/181 (1.10%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Joint injury  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  1/114 (0.88%) 
Metabolism and nutrition disorders             
Hypokalaemia  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Endometrial cancer  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Lung neoplasm malignant  1  1/179 (0.56%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Nervous system disorders             
Convulsion  1  1/179 (0.56%)  0/147 (0.00%)  3/181 (1.66%)  2/132 (1.52%)  3/178 (1.69%)  1/114 (0.88%) 
Dizziness  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  2/178 (1.12%)  0/114 (0.00%) 
Coordination abnormal  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Headache  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Somnolence  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Status epilepticus  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  1/114 (0.88%) 
Myoclonus  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Nerve root compression  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Transient ischaemic attack  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Psychiatric disorders             
Psychotic disorder  1  0/179 (0.00%)  1/147 (0.68%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Acute psychosis  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Deja vu  1  0/179 (0.00%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Mood disorder due to a general medical condition  1  1/179 (0.56%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Renal and urinary disorders             
Atonic urinary bladder  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Urinary incontinence  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Urinary retention  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Dyspnoea  1  1/179 (0.56%)  0/147 (0.00%)  1/181 (0.55%)  0/132 (0.00%)  0/178 (0.00%)  0/114 (0.00%) 
Skin and subcutaneous tissue disorders             
Dermatitis allergic  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Rash macular  1  0/179 (0.00%)  0/147 (0.00%)  0/181 (0.00%)  0/132 (0.00%)  1/178 (0.56%)  0/114 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo - Double Blind (DB) Phase (Titration Plus Maintenance) Placebo - Transition Phase Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 200 mg TID - Transition Phase Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance) Retigabine 300 mg TID - Transition Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   56/179 (31.28%)   38/147 (25.85%)   92/181 (50.83%)   18/132 (13.64%)   117/178 (65.73%)   29/114 (25.44%) 
Ear and labyrinth disorders             
Vertigo  1  5/179 (2.79%)  1/147 (0.68%)  15/181 (8.29%)  1/132 (0.76%)  12/178 (6.74%)  2/114 (1.75%) 
Eye disorders             
Diplopia  1  2/179 (1.12%)  1/147 (0.68%)  12/181 (6.63%)  3/132 (2.27%)  10/178 (5.62%)  0/114 (0.00%) 
Vision blurred  1  3/179 (1.68%)  2/147 (1.36%)  1/181 (0.55%)  1/132 (0.76%)  9/178 (5.06%)  0/114 (0.00%) 
Gastrointestinal disorders             
Nausea  1  7/179 (3.91%)  2/147 (1.36%)  11/181 (6.08%)  3/132 (2.27%)  12/178 (6.74%)  2/114 (1.75%) 
General disorders             
Fatigue  1  5/179 (2.79%)  2/147 (1.36%)  30/181 (16.57%)  2/132 (1.52%)  27/178 (15.17%)  2/114 (1.75%) 
Asthenia  1  4/179 (2.23%)  2/147 (1.36%)  9/181 (4.97%)  2/132 (1.52%)  12/178 (6.74%)  4/114 (3.51%) 
Gait disturbance  1  1/179 (0.56%)  1/147 (0.68%)  6/181 (3.31%)  0/132 (0.00%)  9/178 (5.06%)  0/114 (0.00%) 
Nervous system disorders             
Dizziness  1  12/179 (6.70%)  16/147 (10.88%)  31/181 (17.13%)  3/132 (2.27%)  46/178 (25.84%)  10/114 (8.77%) 
Somnolence  1  18/179 (10.06%)  9/147 (6.12%)  26/181 (14.36%)  3/132 (2.27%)  46/178 (25.84%)  12/114 (10.53%) 
Headache  1  26/179 (14.53%)  8/147 (5.44%)  20/181 (11.05%)  4/132 (3.03%)  31/178 (17.42%)  7/114 (6.14%) 
Tremor  1  4/179 (2.23%)  2/147 (1.36%)  3/181 (1.66%)  1/132 (0.76%)  16/178 (8.99%)  1/114 (0.88%) 
Memory impairment  1  3/179 (1.68%)  2/147 (1.36%)  7/181 (3.87%)  1/132 (0.76%)  11/178 (6.18%)  1/114 (0.88%) 
Disturbance in attention  1  4/179 (2.23%)  2/147 (1.36%)  13/181 (7.18%)  1/132 (0.76%)  10/178 (5.62%)  2/114 (1.75%) 
Coordination abnormal  1  3/179 (1.68%)  3/147 (2.04%)  11/181 (6.08%)  1/132 (0.76%)  8/178 (4.49%)  3/114 (2.63%) 
Psychiatric disorders             
Confusional state  1  0/179 (0.00%)  1/147 (0.68%)  3/181 (1.66%)  1/132 (0.76%)  9/178 (5.06%)  0/114 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00235755     History of Changes
Other Study ID Numbers: VRX-RET-E22-302
First Submitted: October 6, 2005
First Posted: October 10, 2005
Results First Submitted: July 7, 2011
Results First Posted: November 7, 2011
Last Update Posted: April 21, 2017