Trial Outcomes & Findings for Retigabine Efficacy and Safety Trial for Partial Onset Refractory Seizures in Epilepsy (NCT NCT00235755)
NCT ID: NCT00235755
Last Updated: 2017-04-21
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 valu es indicate a reduction in seizure frequency.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
539 participants
Primary outcome timeframe
Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)
Results posted on
2017-04-21
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
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 200 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. 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 300 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. Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the 12-week Maintenance Phase.
|
|---|---|---|---|
|
4-Week Titration Phase
STARTED
|
179
|
181
|
179
|
|
4-Week Titration Phase
COMPLETED
|
168
|
162
|
153
|
|
4-Week Titration Phase
NOT COMPLETED
|
11
|
19
|
26
|
|
12-Week Maintenance Phase
STARTED
|
168
|
162
|
153
|
|
12-Week Maintenance Phase
COMPLETED
|
152
|
135
|
122
|
|
12-Week Maintenance Phase
NOT COMPLETED
|
16
|
27
|
31
|
Reasons for withdrawal
| Measure |
Placebo
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 200 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. 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 300 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. Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the 12-week Maintenance Phase.
|
|---|---|---|---|
|
4-Week Titration Phase
Adverse Event
|
6
|
14
|
20
|
|
4-Week Titration Phase
Lost to Follow-up
|
0
|
1
|
1
|
|
4-Week Titration Phase
Protocol Violation
|
2
|
2
|
1
|
|
4-Week Titration Phase
Withdrawal by Subject
|
1
|
2
|
3
|
|
4-Week Titration Phase
Participant Did Not Receive Study Drug
|
0
|
0
|
1
|
|
4-Week Titration Phase
Randomization Occurred in Error
|
1
|
0
|
0
|
|
4-Week Titration Phase
Prolonged QT Interval at Visit 3
|
1
|
0
|
0
|
|
12-Week Maintenance Phase
Adverse Event
|
8
|
12
|
26
|
|
12-Week Maintenance Phase
Lost to Follow-up
|
2
|
3
|
0
|
|
12-Week Maintenance Phase
Lack of Efficacy
|
5
|
0
|
0
|
|
12-Week Maintenance Phase
Protocol Violation
|
0
|
4
|
2
|
|
12-Week Maintenance Phase
Withdrawal by Subject
|
0
|
8
|
3
|
|
12-Week Maintenance Phase
Abnormal Electrocardiogram Test Result
|
1
|
0
|
0
|
Baseline Characteristics
Retigabine Efficacy and Safety Trial for Partial Onset Refractory Seizures in Epilepsy
Baseline characteristics by cohort
| Measure |
Placebo - Double Blind (DB) Phase (Titration Plus Maintenance)
n=179 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=181 Participants
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 300 mg TID - DB Phase (Titration Plus Maintenance)
n=178 Participants
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
n=538 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
37.7 Years
STANDARD_DEVIATION 11.75 • n=5 Participants
|
37.5 Years
STANDARD_DEVIATION 12.02 • n=7 Participants
|
37.7 Years
STANDARD_DEVIATION 12.77 • n=5 Participants
|
37.6 Years
STANDARD_DEVIATION 12.16 • n=4 Participants
|
|
Sex: Female, Male
Female
|
90 Participants
n=5 Participants
|
105 Participants
n=7 Participants
|
85 Participants
n=5 Participants
|
280 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
89 Participants
n=5 Participants
|
76 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
258 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
169 participants
n=5 Participants
|
173 participants
n=7 Participants
|
170 participants
n=5 Participants
|
512 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
African-American (black)
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Mixed Race
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
16 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)Population: 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.
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.
Outcome measures
| Measure |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=179 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=176 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=175 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
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)
|
-27.9 percent change in seizure frequency
Interval -94.0 to 250.0
|
-15.9 percent change in seizure frequency
Interval -100.0 to 1712.0
|
-39.9 percent change in seizure frequency
Interval -100.0 to 226.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 5 through Week 16Population: 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.
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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=158 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=164 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=149 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Number of Participants Classified as Responders and Non-responders During the Maintenance Phase
Responders
|
61 participants
|
31 participants
|
70 participants
|
—
|
—
|
—
|
|
Number of Participants Classified as Responders and Non-responders During the Maintenance Phase
Non-responders
|
97 participants
|
133 participants
|
79 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 1 through Week 16Population: ITT FDA Population
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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=178 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=179 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=181 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Number of Participants Who Were Responders and Non-responders During the DB Phase
Responders
|
70 participants
|
31 participants
|
57 participants
|
—
|
—
|
—
|
|
Number of Participants Who Were Responders and Non-responders During the DB Phase
Non-responders
|
108 participants
|
148 participants
|
124 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 5 through Week 16Population: ITT EMEA Population
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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=149 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=164 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=158 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
|
-44.3 Percent change in seizure frequency
Interval -100.0 to 714.0
|
-17.4 Percent change in seizure frequency
Interval -100.0 to 1589.0
|
-35.3 Percent change in seizure frequency
Interval -100.0 to 253.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 16Population: ITT FDA Population
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.
Outcome measures
| Measure |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=178 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=179 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=181 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
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
|
27 participants
|
12 participants
|
16 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
|
43 participants
|
19 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
|
41 participants
|
39 participants
|
38 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
|
24 participants
|
43 participants
|
38 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
|
43 participants
|
66 participants
|
48 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 16Population: ITT FDA Population
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.
Outcome measures
| Measure |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=178 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=179 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=181 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
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
Reduction: 90% to 100%
|
11 participants
|
3 participants
|
5 participants
|
—
|
—
|
—
|
|
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
Reduction: 80% to <90%
|
14 participants
|
4 participants
|
8 participants
|
—
|
—
|
—
|
|
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
Reduction: 70% to <80%
|
7 participants
|
8 participants
|
11 participants
|
—
|
—
|
—
|
|
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
Reduction: 60% to <70%
|
21 participants
|
7 participants
|
14 participants
|
—
|
—
|
—
|
|
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
Reduction: 50% to <60%
|
17 participants
|
9 participants
|
19 participants
|
—
|
—
|
—
|
|
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
Reduction: 40% to <50%
|
17 participants
|
9 participants
|
13 participants
|
—
|
—
|
—
|
|
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
Reduction: 30% to <40%
|
21 participants
|
15 participants
|
16 participants
|
—
|
—
|
—
|
|
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
Reduction: 20% to <30%
|
9 participants
|
24 participants
|
16 participants
|
—
|
—
|
—
|
|
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
Reduction: 10% to <20%
|
10 participants
|
18 participants
|
18 participants
|
—
|
—
|
—
|
|
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
Reduction: >0% to <10%
|
8 participants
|
16 participants
|
13 participants
|
—
|
—
|
—
|
|
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
Increase: 0% to 10%
|
11 participants
|
20 participants
|
11 participants
|
—
|
—
|
—
|
|
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
Increase: >10% to 20%
|
7 participants
|
13 participants
|
9 participants
|
—
|
—
|
—
|
|
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
Increase: >20% to 30%
|
1 participants
|
8 participants
|
3 participants
|
—
|
—
|
—
|
|
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
Increase: >30%
|
24 participants
|
25 participants
|
25 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 5 through Week 16Population: ITT EMEA Population
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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=149 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=164 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=158 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
>75% reduction
|
30 participants
|
11 participants
|
27 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
|
40 participants
|
20 participants
|
34 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
|
49 participants
|
83 participants
|
60 participants
|
—
|
—
|
—
|
|
Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
No reduction
|
30 participants
|
50 participants
|
37 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 5 through Week 16Population: ITT EMEA Population
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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=149 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=164 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=158 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
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
|
11 participants
|
28 participants
|
14 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
|
19 participants
|
22 participants
|
23 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
|
119 participants
|
114 participants
|
121 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 16Population: ITT FDA Population
New seizure types included those seizures which were not reported by any participant at Baseline.
Outcome measures
| Measure |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=178 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=179 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=181 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
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
|
9 participants
|
8 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
|
9 participants
|
6 participants
|
5 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
|
3 participants
|
5 participants
|
6 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
|
3 participants
|
0 participants
|
0 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
|
1 participants
|
3 participants
|
2 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 seizures
|
1 participants
|
3 participants
|
0 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
|
4 participants
|
1 participants
|
4 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
Unclassified seizures
|
0 participants
|
0 participants
|
1 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 1 through Week 16Population: ITT FDA Population. Only participants with 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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=175 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=176 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=179 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
Seizure-free
|
7 participants
|
2 participants
|
0 participants
|
—
|
—
|
—
|
|
Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
Not seizure-free
|
168 participants
|
174 participants
|
179 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 5 through Week 16Population: ITT EMEA Population
Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase.
Outcome measures
| Measure |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=149 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=164 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=158 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Number of Participants Who Were Seizure-free During the Maintenance Phase
Not seizure-free
|
142 participants
|
162 participants
|
153 participants
|
—
|
—
|
—
|
|
Number of Participants Who Were Seizure-free During the Maintenance Phase
Seizure-free
|
7 participants
|
2 participants
|
5 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 1 through Week 16Population: ITT FDA Population. 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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=175 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=176 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=179 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)
|
82.1 percentage of days
Interval 0.0 to 100.0
|
77.8 percentage of days
Interval 0.0 to 100.0
|
79.5 percentage of days
Interval 0.0 to 99.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 5 through Week 16Population: ITT EMEA Population
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%.
Outcome measures
| Measure |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=149 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=164 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=158 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Percentage of Seizure-free Days During the Maintenance Phase
|
84.5 percentage of days
Interval 0.0 to 100.0
|
78.1 percentage of days
Interval 0.0 to 100.0
|
81.6 percentage of days
Interval 0.0 to 100.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 16/end of treatment phasePopulation: ITT EMEA Population
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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=149 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=164 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=158 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase
|
2.9 scores on a scale
Standard Deviation 1.21
|
3.2 scores on a scale
Standard Deviation 0.99
|
2.9 scores on a scale
Standard Deviation 1.05
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 16/end of treatment phasePopulation: ITT EMEA Population. Only participants with post-baseline PGI scores were included in the analysis.
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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=139 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=155 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=149 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Patient Global Impression (PGI) Score at the End of the Maintenance Phase
|
3.0 scores on a scale
Standard Deviation 1.43
|
3.3 scores on a scale
Standard Deviation 1.00
|
2.9 scores on a scale
Standard Deviation 1.11
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: End of Baseline (Week 0), Weeks 4, 8, and 16Population: 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.
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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=166 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=165 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=173 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
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
Baseline, n=165, 173, 166
|
52.1 scores on a scale
Standard Deviation 15.93
|
53.3 scores on a scale
Standard Deviation 16.62
|
56.0 scores on a scale
Standard Deviation 17.45
|
—
|
—
|
—
|
|
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
Week 4 (Titration Phase), n=155, 155, 149)
|
52.7 scores on a scale
Standard Deviation 16.94
|
55.4 scores on a scale
Standard Deviation 16.41
|
57.3 scores on a scale
Standard Deviation 18.12
|
—
|
—
|
—
|
|
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
Week 8 (Maintenance Phase), n=141, 146, 127
|
52.7 scores on a scale
Standard Deviation 16.47
|
55.3 scores on a scale
Standard Deviation 17.05
|
59.6 scores on a scale
Standard Deviation 17.32
|
—
|
—
|
—
|
|
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
Week 16 (Maintenance Phase), n=143, 133, 123
|
53.2 scores on a scale
Standard Deviation 16.38
|
54.7 scores on a scale
Standard Deviation 16.82
|
59.1 scores on a scale
Standard Deviation 16.57
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 1 through Week 16Population: 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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=178 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=179 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=181 Participants
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
|
Placebo - Transition Phase
n=147 Participants
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 200 mg TID - Transition Phase
n=132 Participants
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 300 mg TID - Transition Phase
n=114 Participants
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
|
|---|---|---|---|---|---|---|
|
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Protenuria
|
0 participants
|
3 participants
|
2 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Hyperlipidemia
|
0 participants
|
3 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Hypercholesterolemia
|
1 participants
|
2 participants
|
4 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Hematuria
|
2 participants
|
2 participants
|
5 participants
|
1 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Week 1 through Week 16Population: 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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=178 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=179 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=181 Participants
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
|
Placebo - Transition Phase
n=147 Participants
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 200 mg TID - Transition Phase
n=132 Participants
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 300 mg TID - Transition Phase
n=114 Participants
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
|
|---|---|---|---|---|---|---|
|
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Dysuria
|
4 participants
|
0 participants
|
3 participants
|
0 participants
|
0 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
|
4 participants
|
0 participants
|
1 participants
|
0 participants
|
0 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
|
2 participants
|
4 participants
|
1 participants
|
0 participants
|
0 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 hesitation
|
1 participants
|
3 participants
|
6 participants
|
3 participants
|
1 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)
Haematuria
|
2 participants
|
2 participants
|
5 participants
|
1 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline (Week -7 through 0), Weeks 8 and 16Population: 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 16 minus the value at Baseline.
Outcome measures
| Measure |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=115 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=143 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=134 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase
Week 8, n=143, 134, 121
|
0 milliliters
Interval -162.0 to 165.0
|
0 milliliters
Interval -107.0 to 148.0
|
0 milliliters
Interval -195.0 to 400.0
|
—
|
—
|
—
|
|
Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase
Week 16, n=141, 131, 115
|
0 milliliters
Interval -262.0 to 173.0
|
0 milliliters
Interval -185.0 to 232.0
|
0 milliliters
Interval -195.0 to 609.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 2 and 4 of Titration Phase and Weeks 6, 8, 12, and 16 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 |
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
n=175 Participants
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
|
Placebo - DB Phase (Titration Plus Maintenance)
n=174 Participants
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=180 Participants
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
|
Placebo - Transition 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 200 mg TID - Transition Phase
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 300 mg TID - Transition Phase
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
|
|---|---|---|---|---|---|---|
|
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
Week 2, n=174, 180, 175
|
3 participants
|
0 participants
|
3 participants
|
—
|
—
|
—
|
|
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
Week 4, n=169, 172, 167
|
8 participants
|
0 participants
|
7 participants
|
—
|
—
|
—
|
|
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
Week 6, n=169, 165, 152
|
7 participants
|
1 participants
|
8 participants
|
—
|
—
|
—
|
|
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
Week 8, n=161, 160, 149
|
7 participants
|
1 participants
|
9 participants
|
—
|
—
|
—
|
|
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
Week 12, n=159, 151, 144
|
13 participants
|
6 participants
|
15 participants
|
—
|
—
|
—
|
|
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
Week 16, n=153, 139, 132
|
12 participants
|
4 participants
|
13 participants
|
—
|
—
|
—
|
Adverse Events
Placebo - Double Blind (DB) Phase (Titration Plus Maintenance)
Serious events: 7 serious events
Other events: 56 other events
Deaths: 0 deaths
Placebo - Transition Phase
Serious events: 2 serious events
Other events: 38 other events
Deaths: 0 deaths
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)
Serious events: 14 serious events
Other events: 92 other events
Deaths: 0 deaths
Retigabine 200 mg TID - Transition Phase
Serious events: 3 serious events
Other events: 18 other events
Deaths: 0 deaths
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)
Serious events: 15 serious events
Other events: 117 other events
Deaths: 0 deaths
Retigabine 300 mg TID - Transition Phase
Serious events: 3 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo - Double Blind (DB) Phase (Titration Plus Maintenance)
n=179 participants at risk
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
|
Placebo - Transition Phase
n=147 participants at risk
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=181 participants at risk
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 200 mg TID - Transition Phase
n=132 participants at risk
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 300 mg TID - DB Phase (Titration Plus Maintenance)
n=178 participants at risk
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 300 mg TID - Transition Phase
n=114 participants at risk
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
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
Convulsion
|
0.56%
1/179
|
0.00%
0/147
|
1.7%
3/181
|
1.5%
2/132
|
1.7%
3/178
|
0.88%
1/114
|
|
Nervous system disorders
Dizziness
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
1.1%
2/178
|
0.00%
0/114
|
|
Nervous system disorders
Coordination abnormal
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Nervous system disorders
Headache
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Nervous system disorders
Somnolence
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.88%
1/114
|
|
Nervous system disorders
Myoclonus
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Nervous system disorders
Nerve root compression
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Renal and urinary disorders
Atonic urinary bladder
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
General disorders
Sudden unexplained death in epilepsy
|
0.56%
1/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
General disorders
Gait disturbance
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
General disorders
Chest pain
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
General disorders
Fatigue
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Gastrointestinal disorders
Abdominal pain
|
1.1%
2/179
|
0.68%
1/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.56%
1/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.56%
1/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/179
|
0.68%
1/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Psychiatric disorders
Acute psychosis
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Psychiatric disorders
Deja vu
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Psychiatric disorders
Mood disorder due to a general medical condition
|
0.56%
1/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Infections and infestations
Erysipelas
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Infections and infestations
Sepsis
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.76%
1/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Eye disorders
Corneal erosion
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Eye disorders
Visual disturbance
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.56%
1/178
|
0.00%
0/114
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.56%
1/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.56%
1/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Hepatobiliary disorders
Cholecystitis
|
1.1%
2/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/179
|
0.68%
1/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.56%
1/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
0.00%
0/179
|
0.00%
0/147
|
1.1%
2/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.00%
0/179
|
0.00%
0/147
|
0.00%
0/181
|
0.00%
0/132
|
0.00%
0/178
|
0.88%
1/114
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/179
|
0.00%
0/147
|
0.55%
1/181
|
0.00%
0/132
|
0.00%
0/178
|
0.00%
0/114
|
Other adverse events
| Measure |
Placebo - Double Blind (DB) Phase (Titration Plus Maintenance)
n=179 participants at risk
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
|
Placebo - Transition Phase
n=147 participants at risk
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 200 mg TID - DB Phase (Titration Plus Maintenance)
n=181 participants at risk
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 200 mg TID - Transition Phase
n=132 participants at risk
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 300 mg TID - DB Phase (Titration Plus Maintenance)
n=178 participants at risk
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 300 mg TID - Transition Phase
n=114 participants at risk
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
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
Dizziness
|
6.7%
12/179
|
10.9%
16/147
|
17.1%
31/181
|
2.3%
3/132
|
25.8%
46/178
|
8.8%
10/114
|
|
Nervous system disorders
Somnolence
|
10.1%
18/179
|
6.1%
9/147
|
14.4%
26/181
|
2.3%
3/132
|
25.8%
46/178
|
10.5%
12/114
|
|
Nervous system disorders
Headache
|
14.5%
26/179
|
5.4%
8/147
|
11.0%
20/181
|
3.0%
4/132
|
17.4%
31/178
|
6.1%
7/114
|
|
General disorders
Fatigue
|
2.8%
5/179
|
1.4%
2/147
|
16.6%
30/181
|
1.5%
2/132
|
15.2%
27/178
|
1.8%
2/114
|
|
Nervous system disorders
Tremor
|
2.2%
4/179
|
1.4%
2/147
|
1.7%
3/181
|
0.76%
1/132
|
9.0%
16/178
|
0.88%
1/114
|
|
Ear and labyrinth disorders
Vertigo
|
2.8%
5/179
|
0.68%
1/147
|
8.3%
15/181
|
0.76%
1/132
|
6.7%
12/178
|
1.8%
2/114
|
|
Gastrointestinal disorders
Nausea
|
3.9%
7/179
|
1.4%
2/147
|
6.1%
11/181
|
2.3%
3/132
|
6.7%
12/178
|
1.8%
2/114
|
|
General disorders
Asthenia
|
2.2%
4/179
|
1.4%
2/147
|
5.0%
9/181
|
1.5%
2/132
|
6.7%
12/178
|
3.5%
4/114
|
|
Nervous system disorders
Memory impairment
|
1.7%
3/179
|
1.4%
2/147
|
3.9%
7/181
|
0.76%
1/132
|
6.2%
11/178
|
0.88%
1/114
|
|
Eye disorders
Diplopia
|
1.1%
2/179
|
0.68%
1/147
|
6.6%
12/181
|
2.3%
3/132
|
5.6%
10/178
|
0.00%
0/114
|
|
Nervous system disorders
Disturbance in attention
|
2.2%
4/179
|
1.4%
2/147
|
7.2%
13/181
|
0.76%
1/132
|
5.6%
10/178
|
1.8%
2/114
|
|
Eye disorders
Vision blurred
|
1.7%
3/179
|
1.4%
2/147
|
0.55%
1/181
|
0.76%
1/132
|
5.1%
9/178
|
0.00%
0/114
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/179
|
0.68%
1/147
|
1.7%
3/181
|
0.76%
1/132
|
5.1%
9/178
|
0.00%
0/114
|
|
Nervous system disorders
Coordination abnormal
|
1.7%
3/179
|
2.0%
3/147
|
6.1%
11/181
|
0.76%
1/132
|
4.5%
8/178
|
2.6%
3/114
|
|
General disorders
Gait disturbance
|
0.56%
1/179
|
0.68%
1/147
|
3.3%
6/181
|
0.00%
0/132
|
5.1%
9/178
|
0.00%
0/114
|
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