Trial Outcomes & Findings for Retigabine (Adjunctive Therapy) Efficacy and Safety Study for Partial Onset Refractory Seizures in Epilepsy (NCT NCT00232596)
NCT ID: NCT00232596
Last Updated: 2016-12-08
Results Overview
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 values indicate a reduction in seizure frequency.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
306 participants
Primary outcome timeframe
Baseline (Week -7 through Week 0), Week 1 through Week 18
Results posted on
2016-12-08
Participant Flow
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.
Participant milestones
| Measure |
Placebo
Titration Phase: matching placebo tablets of dummy strengths of 50 milligrams (mg), 100 mg, and 300 mg administered orally thrice a day (TID) for 6 weeks. Maintenance Phase: matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 12 weeks.
|
Retigabine
Titration Phase: retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID with a starting daily dose of 300 mg/day (in 3 equally divided doses). The dose increased weekly by 150 mg/day (50 mg TID) for the 6 weeks of the Titration Phase to a target daily dose of 1200 mg/day (400 mg TID) by the beginning of Week 7 of treatment. Maintenance Phase: Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 12 weeks in participants who tolerated this dose. Participants who could not tolerate the 1200 mg/day dose were allowed to reduce the dose to 1050 mg/day (350 mg TID) at the end of the first week and then maintain this dose for the remainder of the 12 weeks.
|
|---|---|---|
|
6-Week Titration Phase
STARTED
|
152
|
154
|
|
6-Week Titration Phase
COMPLETED
|
138
|
125
|
|
6-Week Titration Phase
NOT COMPLETED
|
14
|
29
|
|
12-Week Maintenance Phase
STARTED
|
138
|
125
|
|
12-Week Maintenance Phase
COMPLETED
|
126
|
97
|
|
12-Week Maintenance Phase
NOT COMPLETED
|
12
|
28
|
Reasons for withdrawal
| Measure |
Placebo
Titration Phase: matching placebo tablets of dummy strengths of 50 milligrams (mg), 100 mg, and 300 mg administered orally thrice a day (TID) for 6 weeks. Maintenance Phase: matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 12 weeks.
|
Retigabine
Titration Phase: retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID with a starting daily dose of 300 mg/day (in 3 equally divided doses). The dose increased weekly by 150 mg/day (50 mg TID) for the 6 weeks of the Titration Phase to a target daily dose of 1200 mg/day (400 mg TID) by the beginning of Week 7 of treatment. Maintenance Phase: Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 12 weeks in participants who tolerated this dose. Participants who could not tolerate the 1200 mg/day dose were allowed to reduce the dose to 1050 mg/day (350 mg TID) at the end of the first week and then maintain this dose for the remainder of the 12 weeks.
|
|---|---|---|
|
6-Week Titration Phase
Adverse Event
|
6
|
19
|
|
6-Week Titration Phase
Failed to Return
|
2
|
1
|
|
6-Week Titration Phase
Unsatisfactory Response - Efficacy
|
1
|
2
|
|
6-Week Titration Phase
Protocol Violation
|
1
|
3
|
|
6-Week Titration Phase
Participant Request Unrelated to Study
|
1
|
0
|
|
6-Week Titration Phase
Other
|
3
|
3
|
|
6-Week Titration Phase
Participant Did Not Receive Study Drug
|
0
|
1
|
|
12-Week Maintenance Phase
Adverse Event
|
7
|
22
|
|
12-Week Maintenance Phase
Unsatisfactory Response -Efficacy
|
1
|
2
|
|
12-Week Maintenance Phase
Protocol Violation
|
3
|
1
|
|
12-Week Maintenance Phase
Other
|
1
|
3
|
Baseline Characteristics
Retigabine (Adjunctive Therapy) Efficacy and Safety Study for Partial Onset Refractory Seizures in Epilepsy
Baseline characteristics by cohort
| Measure |
Placebo - Double-blind (DB) Phase (Titration + Maintenance)
n=152 Participants
Matching placebo tablets of dummy strengths of 50 milligrams (mg), 100 mg, and 300 mg administered orally thrice a day (TID) for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=153 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Total
n=305 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36.7 Years
STANDARD_DEVIATION 11.63 • n=5 Participants
|
37.7 Years
STANDARD_DEVIATION 12.55 • n=7 Participants
|
37.2 Years
STANDARD_DEVIATION 12.09 • n=5 Participants
|
|
Gender
Female
|
80 Participants
n=5 Participants
|
85 Participants
n=7 Participants
|
165 Participants
n=5 Participants
|
|
Gender
Male
|
72 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
78 participants
n=5 Participants
|
90 participants
n=7 Participants
|
168 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African - American (Black)
|
15 participants
n=5 Participants
|
15 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
48 participants
n=5 Participants
|
39 participants
n=7 Participants
|
87 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Mestizo
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Mixed Race
|
8 participants
n=5 Participants
|
8 participants
n=7 Participants
|
16 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 18Population: Intent-to-Treat (ITT) Population for Food and Drug Administration (FDA) review: all randomized participants (par.) who received at least one dose of the study drug. Only par. with baseline and post-baseline measures were analyzed. Two par. in each treatment arm did not have post-baseline measures and were thus not included in this analysis.
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 values indicate a reduction in seizure frequency.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=150 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=151 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
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)
|
-17.5 percent change in seizure frequency
Interval -90.0 to 628.0
|
-44.3 percent change in seizure frequency
Interval -100.0 to 302.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 7 through Week 18Population: Intent-to-Treat (ITT) Population for European Medicines Agency (EMEA) review: all randomized participants who received at least one dose of study drug in the Maintenance Phase and had at least one seizure measurement (whether or not they had a seizure) recorded in the Maintenance Phase
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=137 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=119 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Number of Participants Who Were Responders and Non-responders in the Maintenance Phase
Responders
|
31 participants
|
66 participants
|
—
|
—
|
|
Number of Participants Who Were Responders and Non-responders in the Maintenance Phase
Non-responders
|
106 participants
|
53 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 1 through Week 18Population: ITT Population for FDA review
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=152 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=153 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Number of Participants Who Were Responders and Non-responders in the DB Phase
Responders
|
27 participants
|
68 participants
|
—
|
—
|
|
Number of Participants Who Were Responders and Non-responders in the DB Phase
Non-responders
|
125 participants
|
85 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 7 through Week 18Population: ITT Population for EMEA review
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=137 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=119 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
|
-18.9 percent change in seizure frequency
Interval -100.0 to 1382.0
|
-54.5 percent change in seizure frequency
Interval -100.0 to 660.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 18Population: ITT Population for FDA review
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 were included in the "No reduction" category.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=152 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=153 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
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
75% to 100% reduction
|
6 participants
|
27 participants
|
—
|
—
|
|
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
50% to <75% reduction
|
21 participants
|
41 participants
|
—
|
—
|
|
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
25% to <50% reduction
|
37 participants
|
20 participants
|
—
|
—
|
|
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
>0 to <25% reduction
|
33 participants
|
26 participants
|
—
|
—
|
|
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
No reduction
|
55 participants
|
39 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 18Population: ITT Population for FDA review
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 0-10% increase category.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=152 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=153 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: 90% to 100%
|
0 participants
|
12 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: 80% to <90%
|
5 participants
|
11 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: 70% to <80%
|
4 participants
|
10 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: 60% to <70%
|
7 participants
|
20 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: 50% to <60%
|
11 participants
|
15 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: 40% to <50%
|
11 participants
|
10 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: 30% to <40%
|
13 participants
|
6 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: 20% to <30%
|
19 participants
|
12 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: 10% to <20%
|
13 participants
|
10 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Reduction: >0% to <10%
|
14 participants
|
8 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Increase: 0% to 10%
|
14 participants
|
10 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Increase: >10% to 20%
|
12 participants
|
5 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Increase: >20% to 30%
|
4 participants
|
4 participants
|
—
|
—
|
|
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Increase: >30%
|
25 participants
|
20 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 7 through Week 18Population: ITT Population for EMEA review
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).
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=137 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=119 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
>75% reduction
|
13 participants
|
37 participants
|
—
|
—
|
|
Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
50% to 75% reduction
|
18 participants
|
29 participants
|
—
|
—
|
|
Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
>0 to <50% reduction
|
65 participants
|
33 participants
|
—
|
—
|
|
Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
No reduction
|
41 participants
|
20 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 7 through Week 18Population: ITT Population for EMEA review.
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=137 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=119 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
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
0% to 25% increase
|
20 participants
|
4 participants
|
—
|
—
|
|
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
>=25% increase
|
21 participants
|
16 participants
|
—
|
—
|
|
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
>0% reduction
|
96 participants
|
99 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 18Population: ITT Population for FDA review
New seizure types included those seizures which were not reported by any participant at Baseline.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=152 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=153 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
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
No new seizure type
|
33 participants
|
42 participants
|
—
|
—
|
|
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
Partial seizures without motor signs
|
12 participants
|
17 participants
|
—
|
—
|
|
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
Partial evolving to secondarily generalized
|
7 participants
|
12 participants
|
—
|
—
|
|
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
Complex partial seizures
|
5 participants
|
11 participants
|
—
|
—
|
|
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
Partial seizures with motor signs
|
11 participants
|
7 participants
|
—
|
—
|
|
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
Flurries
|
3 participants
|
1 participants
|
—
|
—
|
|
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
Tonic-clonic seizures
|
0 participants
|
1 participants
|
—
|
—
|
|
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
Atonic seizures
|
1 participants
|
0 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 1 through Week 18Population: ITT Population for FDA review. Only participants who had post-baseline seizure data were included in the analysis.
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=150 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=151 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
Seizure free
|
0 participants
|
3 participants
|
—
|
—
|
|
Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
Not seizure free
|
150 participants
|
148 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 7 through Week 18Population: ITT Population for EMEA review
Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=137 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=119 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Number of Participants Who Were Seizure-free During the Maintenance Phase
Seizure free
|
2 participants
|
9 participants
|
—
|
—
|
|
Number of Participants Who Were Seizure-free During the Maintenance Phase
Not seizure free
|
135 participants
|
110 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 1 through Week 18Population: ITT Population for FDA review. Only participants who had post-baseline seizure data were included in the analysis.
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%.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=150 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=151 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)
|
77.3 percentage of days
Interval 0.0 to 98.0
|
84.1 percentage of days
Interval 0.0 to 100.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 7 through Week 18Population: ITT Population for EMEA review
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 DB period divided by the number of days in the DB period x 100%.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=137 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=119 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Percentage of Seizure-free Days During the Maintenance Phase
|
78.2 percentage of days
Interval 0.0 to 100.0
|
86.9 percentage of days
Interval 0.0 to 100.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 18/end of treatment phasePopulation: ITT Population for EMEA review. Only participants who had CGI-I scores were analyzed.
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=137 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=117 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase
|
3.2 scores on a scale
Standard Deviation 1.11
|
2.7 scores on a scale
Standard Deviation 1.30
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 18/end of treatment phasePopulation: ITT Population for EMEA review. Only participants who had a PGI score were analyzed.
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=120 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=100 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Patient Global Impression (PGI) Score at the End of the Maintenance Phase
|
2.9 scores on a scale
Standard Deviation 1.16
|
2.9 scores on a scale
Standard Deviation 1.23
|
—
|
—
|
SECONDARY outcome
Timeframe: End of Baseline (Week 0), Weeks 6, 10, and 18Population: Safety Population: all randomized participants who received at least 1 dose of retigabine or placebo. Participants who were cognitively impaired and could not complete the QOLIE-31-P assessment were not analyzed. The number of participants analyzed differs by week because not all participants completed the questionnaire at the indicated weeks.
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=139 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=137 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Quality of Life (QOL) Assessed by QOL in Epilepsy-Problems Questionnaire (QOLIE-31-P) at Baseline (Week 0) and Weeks 6, 10, and 18
Baseline (Week -7 through Week 0), n=139, 137
|
52.6 scores on a scale
Standard Deviation 15.55
|
55.6 scores on a scale
Standard Deviation 17.95
|
—
|
—
|
|
Quality of Life (QOL) Assessed by QOL in Epilepsy-Problems Questionnaire (QOLIE-31-P) at Baseline (Week 0) and Weeks 6, 10, and 18
Week 6 (Titration Phase), n=127, 108
|
55.2 scores on a scale
Standard Deviation 16.71
|
55.7 scores on a scale
Standard Deviation 19.18
|
—
|
—
|
|
Quality of Life (QOL) Assessed by QOL in Epilepsy-Problems Questionnaire (QOLIE-31-P) at Baseline (Week 0) and Weeks 6, 10, and 18
Week 10 (Maintenance Phase), n=121, 102
|
57.9 scores on a scale
Standard Deviation 15.57
|
56.2 scores on a scale
Standard Deviation 18.04
|
—
|
—
|
|
Quality of Life (QOL) Assessed by QOL in Epilepsy-Problems Questionnaire (QOLIE-31-P) at Baseline (Week 0) and Weeks 6, 10, and 18
Week 18 (Maintenance Phase), n=116, 85
|
57.3 scores on a scale
Standard Deviation 15.56
|
53.8 scores on a scale
Standard Deviation 17.79
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 1 through Week 24Population: Safety Population
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=152 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=123 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
n=153 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
n=92 Participants
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Bacteria urine
|
1 participants
|
0 participants
|
1 participants
|
2 participants
|
|
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Hematology test abnormal
|
0 participants
|
0 participants
|
1 participants
|
2 participants
|
|
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Urinary sediment present
|
1 participants
|
0 participants
|
0 participants
|
2 participants
|
|
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Urine analysis abnormal
|
3 participants
|
3 participants
|
4 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Week 1 through Week 24Population: Safety Population
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.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=152 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=123 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
n=153 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
n=92 Participants
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Urinary hesitation
|
1 participants
|
2 participants
|
9 participants
|
0 participants
|
|
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Dysuria
|
2 participants
|
2 participants
|
8 participants
|
1 participants
|
|
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Chromaturia
|
0 participants
|
0 participants
|
7 participants
|
0 participants
|
|
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Polyuria
|
1 participants
|
0 participants
|
4 participants
|
0 participants
|
|
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Nephrolithiasis
|
0 participants
|
0 participants
|
4 participants
|
0 participants
|
|
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Hematuria
|
1 participants
|
2 participants
|
2 participants
|
0 participants
|
|
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Urinary retention
|
2 participants
|
2 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Weeks 10 and 18Population: Safety Population. Only participants who remained in the study at the indicated week and who also had a PVR assessment were analyzed.
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 18 minus the value at Baseline.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=111 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=100 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Change From Baseline in Post-void Residual Urine Volume at Weeks 10 and 18 of the DB Treatment Phase
Week 10, n=111, 100
|
-1.0 milliliters
Interval -211.0 to 190.0
|
0.0 milliliters
Interval -163.0 to 413.0
|
—
|
—
|
|
Change From Baseline in Post-void Residual Urine Volume at Weeks 10 and 18 of the DB Treatment Phase
Week 18, n=95, 76
|
-3.0 milliliters
Interval -258.0 to 110.0
|
0.0 milliliters
Interval -184.0 to 257.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 2, 4, 6 of Titration Phase and Weeks 7, 8, 10, 14, and 18 of Maintenance PhasePopulation: Safety Population. Only participants who remained in the study at the indicated week and who also had a body weight assessment were analyzed.
The number of participants with recorded weight gain of \>=7% over their baseline weight was measured.
Outcome measures
| Measure |
Placebo - DB Phase (Titration + Maintenance)
n=149 Participants
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Retigabine - DB Phase (Titration + Maintenance)
n=150 Participants
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine - DB Phase (Titration and Maintenance)
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Number of Participants With a >=7% Increase in Body Weight During Weeks 2, 4, and 6 of theTitration Phase and Weeks 7, 8, 10, 14, and 18 of the Maintenance Phase
Titration Phase, Week 2, n=149, 150
|
0 participants
|
5 participants
|
—
|
—
|
|
Number of Participants With a >=7% Increase in Body Weight During Weeks 2, 4, and 6 of theTitration Phase and Weeks 7, 8, 10, 14, and 18 of the Maintenance Phase
Titration Phase, Week 4, n=145, 144
|
0 participants
|
5 participants
|
—
|
—
|
|
Number of Participants With a >=7% Increase in Body Weight During Weeks 2, 4, and 6 of theTitration Phase and Weeks 7, 8, 10, 14, and 18 of the Maintenance Phase
Titration Phase, Week 6, n=146, 129
|
1 participants
|
6 participants
|
—
|
—
|
|
Number of Participants With a >=7% Increase in Body Weight During Weeks 2, 4, and 6 of theTitration Phase and Weeks 7, 8, 10, 14, and 18 of the Maintenance Phase
Maintenance Phase, Week 7, n=130, 121
|
2 participants
|
9 participants
|
—
|
—
|
|
Number of Participants With a >=7% Increase in Body Weight During Weeks 2, 4, and 6 of theTitration Phase and Weeks 7, 8, 10, 14, and 18 of the Maintenance Phase
Maintenance Phase, Week 8, n=135, 128
|
1 participants
|
10 participants
|
—
|
—
|
|
Number of Participants With a >=7% Increase in Body Weight During Weeks 2, 4, and 6 of theTitration Phase and Weeks 7, 8, 10, 14, and 18 of the Maintenance Phase
Maintenance Phase, Week 10, n=136, 119
|
3 participants
|
15 participants
|
—
|
—
|
|
Number of Participants With a >=7% Increase in Body Weight During Weeks 2, 4, and 6 of theTitration Phase and Weeks 7, 8, 10, 14, and 18 of the Maintenance Phase
Maintenance Phase, Week 14, n=137, 109
|
3 participants
|
18 participants
|
—
|
—
|
|
Number of Participants With a >=7% Increase in Body Weight During Weeks 2, 4, and 6 of theTitration Phase and Weeks 7, 8, 10, 14, and 18 of the Maintenance Phase
Maintenance Phase, Week 18, n=127, 92
|
4 participants
|
17 participants
|
—
|
—
|
Adverse Events
Placebo - Double-blind (DB) Phase (Titration and Maintenance)
Serious events: 8 serious events
Other events: 91 other events
Deaths: 0 deaths
Placebo (DB Phase) and Retigabine (Transition Phase)
Serious events: 6 serious events
Other events: 64 other events
Deaths: 0 deaths
Retigabine - DB Phase (Titration and Maintenance)
Serious events: 19 serious events
Other events: 121 other events
Deaths: 0 deaths
Retigabine (DB Phase) and Retigabine (Transition Phase)
Serious events: 5 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo - Double-blind (DB) Phase (Titration and Maintenance)
n=152 participants at risk
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Placebo (DB Phase) and Retigabine (Transition Phase)
n=123 participants at risk
Participants on placebo during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
Retigabine - DB Phase (Titration and Maintenance)
n=153 participants at risk
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
n=92 participants at risk
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/152
|
0.00%
0/123
|
1.3%
2/153
|
0.00%
0/92
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
1.1%
1/92
|
|
Nervous system disorders
Convulsion
|
0.66%
1/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Nervous system disorders
Aphasia
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Nervous system disorders
Ataxia
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Nervous system disorders
Syncope
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Nervous system disorders
Epilepsy
|
0.66%
1/152
|
0.00%
0/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Nervous system disorders
Migraine
|
0.00%
0/152
|
0.81%
1/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Nervous system disorders
Somnolence
|
0.00%
0/152
|
0.81%
1/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/152
|
0.81%
1/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/152
|
0.00%
0/123
|
2.0%
3/153
|
0.00%
0/92
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/152
|
0.00%
0/123
|
1.3%
2/153
|
0.00%
0/92
|
|
Psychiatric disorders
Depression
|
0.66%
1/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/152
|
0.00%
0/123
|
0.00%
0/153
|
1.1%
1/92
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Metabolism and nutrition disorders
Tetany
|
0.00%
0/152
|
1.6%
2/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
0.00%
0/152
|
1.6%
2/123
|
0.00%
0/153
|
0.00%
0/92
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
General disorders
Gait disturbance
|
0.00%
0/152
|
0.81%
1/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Injury, poisoning and procedural complications
Device malfunction
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Injury, poisoning and procedural complications
Collapse of lung
|
0.66%
1/152
|
0.00%
0/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Investigations
Transaminases increased
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
1.1%
1/92
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
0.00%
0/92
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.66%
1/152
|
0.00%
0/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.66%
1/152
|
0.00%
0/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/152
|
0.81%
1/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Renal and urinary disorders
Urinary retention
|
0.66%
1/152
|
0.81%
1/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/152
|
0.81%
1/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.66%
1/152
|
0.00%
0/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.66%
1/152
|
0.00%
0/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Ear and labyrinth disorders
Vertigo
|
0.66%
1/152
|
0.81%
1/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Cardiac disorders
Atrioventricular block
|
0.66%
1/152
|
0.00%
0/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/152
|
0.00%
0/123
|
0.00%
0/153
|
1.1%
1/92
|
|
Reproductive system and breast disorders
Epididymitis
|
0.66%
1/152
|
0.00%
0/123
|
0.00%
0/153
|
0.00%
0/92
|
|
Vascular disorders
Venous Thrombosis
|
0.00%
0/152
|
0.00%
0/123
|
0.65%
1/153
|
1.1%
1/92
|
Other adverse events
| Measure |
Placebo - Double-blind (DB) Phase (Titration and Maintenance)
n=152 participants at risk
Matching placebo tablets of dummy strengths of 50 mg, 100 mg, and 300 mg administered orally TID for 18 weeks (6 weeks of Titration Phase and 12 weeks of Maintenance Phase)
|
Placebo (DB Phase) and Retigabine (Transition Phase)
n=123 participants at risk
Participants on placebo during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
Retigabine - DB Phase (Titration and Maintenance)
n=153 participants at risk
Retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a target daily dose of 1200 mg/day (400 mg TID) for 18 weeks (6 weeks of the Titration Phase, with dosage increase from 300 mg/day to 1200 mg/day \[weekly increase of 150 mg/day\], and 12 weeks of the Maintenance Phase, with 1200 mg/day or 1050 mg/day \[for participants who could not tolerate 1200 mg/day\])
|
Retigabine (DB Phase) and Retigabine (Transition Phase)
n=92 participants at risk
Participants on retigabine during the DB phase were administered retigabine tablets of strengths 50 mg, 100 mg, and 300 mg administered orally TID for a total daily dose of 1200 mg/day (400 mg TID) for 6 weeks
|
|---|---|---|---|---|
|
Nervous system disorders
Dizziness
|
13.8%
21/152
|
15.4%
19/123
|
40.5%
62/153
|
9.8%
9/92
|
|
Nervous system disorders
Somnolence
|
17.8%
27/152
|
13.0%
16/123
|
31.4%
48/153
|
5.4%
5/92
|
|
General disorders
Fatigue
|
7.9%
12/152
|
8.9%
11/123
|
15.7%
24/153
|
1.1%
1/92
|
|
Psychiatric disorders
Confusional state
|
2.0%
3/152
|
3.3%
4/123
|
13.1%
20/153
|
0.00%
0/92
|
|
Nervous system disorders
Headache
|
18.4%
28/152
|
7.3%
9/123
|
12.4%
19/153
|
5.4%
5/92
|
|
Nervous system disorders
Dysarthria
|
2.0%
3/152
|
5.7%
7/123
|
12.4%
19/153
|
0.00%
0/92
|
|
Infections and infestations
Urinary tract infection
|
8.6%
13/152
|
6.5%
8/123
|
11.8%
18/153
|
4.3%
4/92
|
|
Nervous system disorders
Ataxia
|
3.9%
6/152
|
4.1%
5/123
|
11.1%
17/153
|
1.1%
1/92
|
|
Eye disorders
Vision blurred
|
2.6%
4/152
|
3.3%
4/123
|
11.8%
18/153
|
1.1%
1/92
|
|
Nervous system disorders
Tremor
|
3.9%
6/152
|
0.81%
1/123
|
11.1%
17/153
|
1.1%
1/92
|
|
Gastrointestinal disorders
Nausea
|
6.6%
10/152
|
2.4%
3/123
|
10.5%
16/153
|
1.1%
1/92
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/152
|
2.4%
3/123
|
8.5%
13/153
|
2.2%
2/92
|
|
Infections and infestations
Influenza
|
5.3%
8/152
|
2.4%
3/123
|
7.8%
12/153
|
4.3%
4/92
|
|
Nervous system disorders
Memory impairment
|
4.6%
7/152
|
1.6%
2/123
|
7.8%
12/153
|
2.2%
2/92
|
|
Eye disorders
Diplopia
|
2.6%
4/152
|
3.3%
4/123
|
6.5%
10/153
|
0.00%
0/92
|
|
General disorders
Gait disturbance
|
2.0%
3/152
|
3.3%
4/123
|
6.5%
10/153
|
1.1%
1/92
|
|
Ear and labyrinth disorders
Vertigo
|
2.6%
4/152
|
4.9%
6/123
|
5.9%
9/153
|
0.00%
0/92
|
|
Gastrointestinal disorders
Constipation
|
2.0%
3/152
|
3.3%
4/123
|
5.9%
9/153
|
2.2%
2/92
|
|
Nervous system disorders
Balance disorder
|
0.66%
1/152
|
1.6%
2/123
|
5.9%
9/153
|
1.1%
1/92
|
|
Renal and urinary disorders
Urinary hesitation
|
0.66%
1/152
|
1.6%
2/123
|
5.9%
9/153
|
0.00%
0/92
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
8/152
|
0.81%
1/123
|
4.6%
7/153
|
0.00%
0/92
|
|
Psychiatric disorders
Anxiety
|
2.6%
4/152
|
4.9%
6/123
|
5.2%
8/153
|
1.1%
1/92
|
|
Renal and urinary disorders
Dysuria
|
1.3%
2/152
|
1.6%
2/123
|
5.2%
8/153
|
1.1%
1/92
|
|
Psychiatric disorders
Disorientation
|
0.66%
1/152
|
0.81%
1/123
|
5.2%
8/153
|
1.1%
1/92
|
|
Nervous system disorders
Disturbance in attention
|
0.66%
1/152
|
3.3%
4/123
|
5.2%
8/153
|
1.1%
1/92
|
|
Nervous system disorders
Convulsion
|
5.9%
9/152
|
2.4%
3/123
|
3.9%
6/153
|
1.1%
1/92
|
|
Gastrointestinal disorders
Diarrhoea
|
5.9%
9/152
|
1.6%
2/123
|
3.9%
6/153
|
0.00%
0/92
|
|
Gastrointestinal disorders
Abdominal pain
|
5.3%
8/152
|
2.4%
3/123
|
3.3%
5/153
|
2.2%
2/92
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER