Trial Outcomes & Findings for Assessment of the Efficacy and Safety of 2 Doses of Retigabine Immediate Release (900 mg/Day and 600 mg/Day) Used as Adjunctive Therapy in Adult Asian Subjects With Drug-resistant Partial-onset Seizures (NCT NCT01648101)

Results Overview

A responder is defined as a par. with \>=50% reduction in the 28 day total partial on-set seizure (POS) frequency from the Baseline Phase (BP) to the MP, randomly assigned to retigabine 900 mg/day compared with placebo. The total 28-day POS rate was defined as: (total number of POS over the evaluable period (MP) / number of days of seizure (sz) data in the evaluable period) \*28 days. In the event of one or more innumerable seizures (IS) occurring on a day, these were to be counted as an additional 10 seizures for that day, regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of MP minus start date of the MP minus days on which seizures were recorded as "Not done" + 1). Each occurrence of status epilepticus (SE) was counted as 1 seizure (whether partial or not).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

76 participants

Primary outcome timeframe

Baseline (BL); Week 4 up to Week 16

Results posted on

2018-08-13

Participant Flow

Participants with drug-resistant partial-onset seizures (POS) who were taking 1, 2, or 3 antiepileptic drugs (AEDs) with or without vagus nerve stimulator (VNS); had a 28-day total POS frequency rate \>=4 seizures; and did not have a period of \>=21 consecutive days without a POS over the 8-week Baseline Phase were enrolled in this study.

76 participants (par.) were randomized to study treatment; 75 par. comprised the Intent-to-Treat Population (par. who were randomly assigned to treatment, received \>=1 dose/any portion of a dose of study medication, had Baseline \[BL\] seizure data, and had \>=1 post-BL seizure record between the Titration Phase and the end of the Maintenance Phase).

Participant milestones

Participant milestones
Measure	Placebo Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 600 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Transition Phase (4 Weeks) NOT COMPLETED	5	5	4
Titration Phase (4 Weeks) STARTED	25	26	24
Titration Phase (4 Weeks) COMPLETED	23	23	18
Titration Phase (4 Weeks) NOT COMPLETED	2	3	6
Maintenance Phase (12 Weeks) STARTED	23	23	18
Maintenance Phase (12 Weeks) COMPLETED	20	20	12
Maintenance Phase (12 Weeks) NOT COMPLETED	3	3	6
Transition Phase (4 Weeks) STARTED	17	18	9
Transition Phase (4 Weeks) COMPLETED	12	13	5
Taper/Follow-up Phase (4 Weeks) STARTED	1	2	3
Taper/Follow-up Phase (4 Weeks) COMPLETED	1	1	3
Taper/Follow-up Phase (4 Weeks) NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 600 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Titration Phase (4 Weeks) Protocol Violation	2	1	2
Titration Phase (4 Weeks) Adverse Event	0	2	3
Titration Phase (4 Weeks) Reached Protocol Defined Criteria	0	0	1
Maintenance Phase (12 Weeks) Withdrew Consent	1	0	1
Maintenance Phase (12 Weeks) Lack of Efficacy	1	0	1
Maintenance Phase (12 Weeks) Adverse Event	1	3	4
Transition Phase (4 Weeks) Adverse Event	4	3	2
Transition Phase (4 Weeks) Lack of Efficacy	0	2	0
Transition Phase (4 Weeks) Withdrawal by Subject	0	0	2
Transition Phase (4 Weeks) Study Terminated	1	0	0
Taper/Follow-up Phase (4 Weeks) Lack of Efficacy	0	1	0

Baseline Characteristics

Assessment of the Efficacy and Safety of 2 Doses of Retigabine Immediate Release (900 mg/Day and 600 mg/Day) Used as Adjunctive Therapy in Adult Asian Subjects With Drug-resistant Partial-onset Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Total n=75 Participants Total of all reporting groups
Age, Continuous	36.0 Years STANDARD_DEVIATION 9.43 • n=5 Participants	37.1 Years STANDARD_DEVIATION 10.90 • n=7 Participants	36.3 Years STANDARD_DEVIATION 13.50 • n=5 Participants	36.5 Years STANDARD_DEVIATION 11.27 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	16 Participants n=7 Participants	15 Participants n=5 Participants	45 Participants n=4 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	17 Participants n=5 Participants	16 Participants n=7 Participants	15 Participants n=5 Participants	48 Participants n=4 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	7 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	27 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (BL); Week 4 up to Week 16

Population: ITT Population: all par. who were randomly assigned to treatment; rec'd≥1 dose (or any portion of dose) of study medication; had BL sz data; and had ≥1 post-BL sz record (whether or not they had a sz) between start of TiP and end of MP. Par. who dropped out during TiP were classified as non-responders. For all other par. only MP data were used.

A responder is defined as a par. with \>=50% reduction in the 28 day total partial on-set seizure (POS) frequency from the Baseline Phase (BP) to the MP, randomly assigned to retigabine 900 mg/day compared with placebo. The total 28-day POS rate was defined as: (total number of POS over the evaluable period (MP) / number of days of seizure (sz) data in the evaluable period) \*28 days. In the event of one or more innumerable seizures (IS) occurring on a day, these were to be counted as an additional 10 seizures for that day, regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of MP minus start date of the MP minus days on which seizures were recorded as "Not done" + 1). Each occurrence of status epilepticus (SE) was counted as 1 seizure (whether partial or not).

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Number of Placebo and Retigabine 900 mg Responders During the Maintenance Phase (MP) Responders	—	0 Participants	4 Participants	—
Number of Placebo and Retigabine 900 mg Responders During the Maintenance Phase (MP) Non-Responders	—	25 Participants	20 Participants	—

SECONDARY outcome

Timeframe: Baseline; Week 4 up to Week 16

Population: ITT Population: all par. who were randomly assigned to treatment; rec'd≥1 dose (or any portion of dose) of study medication; had BL sz data; and had ≥1 post-BL sz record (whether or not they had a sz) between start of TiP and end of MP. Par. who dropped out during TiP were classified as non-responders. For all other par. only MP data were used.

A "responder" is defined as a participant experiencing a \>=50% reduction in the 28-day total POS frequency from the BP to the MP, randomly assigned to retigabine 600 mg/day compared to placebo. The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest \[MP\] / number of applicable days in that period) \* 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the MP minus the start date of the MP minus days on which seizures were recorded as "Not Done" during the MP plus 1). Each occurrence of SE was counted as 1 seizure (whether partial status or not).

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Number of Placebo and Retigabine 600 mg Responders During the MP Responders	8 Participants	0 Participants	—	—
Number of Placebo and Retigabine 600 mg Responders During the MP Non-Responders	18 Participants	25 Participants	—	—

SECONDARY outcome

Timeframe: From Baseline up to Week 16

Population: Intent-to-Treat (ITT) Population

A "responder" is defined as a participant experiencing a \>=50% reduction in the 28-day total POS frequency from the BP to the TrP (TiP plus MP). The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest \[TrP\] / number of applicable days in that period) \* 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the TrP minus the start date of the TrP minus days on which seizures were recorded as "Not Done" during the TrP plus 1). Each occurrence of SE was counted as 1 seizure (whether partial status or not).

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Number of Responders From the BP to the Treatment Phase (TrP) Responders	8 Participants	1 Participants	6 Participants	—
Number of Responders From the BP to the Treatment Phase (TrP) Non-Responders	18 Participants	24 Participants	18 Participants	—

SECONDARY outcome

Timeframe: Baseline; Week 4 up to Week 16

Population: ITT Population. Participants who dropped out during the TiP were calculated based on TiP data. For all others, only MP data were used.

The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest \[MP\] / number of applicable days in that period) \* 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the MP minus the start date of the MP minus days on which seizures were recorded as "Not Done" during the MP plus 1. Percent change from Baseline was calculated as: (\[the 28-day PS rate for the period of interest (MP) minus the Baseline 28-day PS rate\] / Baseline 28-day PS rate) \* 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Percent Change From Baseline in the 28-day Total POS Frequency During the MP	-33.90 Percent change Interval -100.0 to 16.3	-22.21 Percent change Interval -48.6 to 61.0	-22.46 Percent change Interval -100.0 to 263.63	—

SECONDARY outcome

Timeframe: From Baseline up to Week 16

Population: ITT Population. Participants who dropped out during the TiP were calculated based on TiP data. For all others both Titration and Maintenance Phase data were used

The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest \[TrP; TiP plus MP\] / number of applicable days in that period) \* 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the TrP minus the start date of the TrP minus days on which seizures were recorded as "Not Done" during the TrP plus 1. Percent change from Baseline was calculated as: (\[the 28-day PS rate for the period of interest (TrP) minus the Baseline 28-day PS rate\] / Baseline 28-day PS rate) \* 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Percent Change From Baseline in the 28-day Total POS Frequency During the TrP	-36.30 Percent change Interval -100.0 to 8.2	-22.55 Percent change Interval -70.5 to 54.8	-26.73 Percent change Interval -100.0 to 176.4	—

SECONDARY outcome

Timeframe: Baseline; Week 4 up to Week 16

Population: ITT Population: Due to the early termination of the study, insufficient data are available to perform these analysis.

The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest \[MP\] / number of applicable days in that period) \* 28. In a case of \>=1 occurrence of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the MP minus the start date of the MP minus days on which seizures were recorded as "Not Done" during the MP plus 1. Percent change from Baseline was calculated as: (\[the 28-day PS rate for the period of interest (MP) minus the Baseline 28-day PS rate\] / Baseline 28-day PS rate) \* 100. A negative percent change indicates a reduction (improvement) from Baseline. There was no theoretical upper limit for worsening. Each occurrence of status epilepticus (SE) was counted as 1 seizure (whether partial status or not).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Baseline up to Week 16

Population: ITT Population: Due to the early termination of the study, insufficient data are available to perform these analysis.

The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest \[TrP; TiP plus MP\] / number of applicable days in that period) \* 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the TrP minus the start date of the TrP minus days on which seizures were recorded as "Not Done" during the TrP plus 1. Percent change from Baseline was calculated as: (\[the 28-day PS rate for the period of interest (TrP) minus the Baseline 28-day PS rate\] / Baseline 28-day PS rate) \* 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline; Week 4 up to Week 16

Population: ITT Population: Due to the early termination of the study, insufficient data are available to perform these analysis.

The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest \[MP\] / number of applicable days in that period) \* 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the MP minus the start date of the MP minus days on which seizures were recorded as "Not Done" during the MP plus 1. Percent change from Baseline was calculated as: (\[the 28-day PS rate for the period of interest (MP) minus the Baseline 28-day PS rate\] / Baseline 28-day PS rate) \* 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Baseline up to Week 16

Population: ITT Population: Due to the early termination of the study, insufficient data are available to perform these analysis.

The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest \[TrP; TiP plus MP\] / number of applicable days in that period) \* 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the TrP minus the start date of the TrP minus days on which seizures were recorded as "Not Done" during the TrP plus 1. Percent change from Baseline was calculated as: (\[the 28-day PS rate for the period of interest (TrP) minus the Baseline 28-day PS rate\] / Baseline 28-day PS rate) \* 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline; Week 4 up to Week 16

Population: ITT Population.

A seizure free-day is defined as a day with non-missing seizure data but without any seizures. A participant was considered to be seizure free during the MP if he/she had no record of countable seizures of any type, no IS, and no SE during the MP. Participants who had one or more days on which they recorded seizures as "Not Done" on the seizure calendar were not disqualified from being considered as seizure free for that day. Participants who did not complete the study or experienced any seizures in the MP were not considered to be seizure free. A participant who completed the study AND had no seizures during the maintenance phase were counted to be seizure free. Also, a completer who only had seizures during the TiP is considered seizure free.

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Number of Participants Who Were Seizure Free During the MP, ITT Population	0 Participants	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to Week 16

Population: ITT Population.

A seizure free-day is defined as a day with non-missing seizure data but without any seizures. A participant was considered to be seizure free during the TrP if he/she had no record of countable seizures of any type, no IS, and no SE during the TrP. Participants who had one or more days on which they recorded seizures as "Not Done" on the seizure calendar were not disqualified from being considered as seizure free for that day. A participant was considered to be seizure free if they experienced no seizures in the TiP or MP regardless of how long they were in the study.

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Number of Participants Who Were Seizure Free During the TrP	1 Participants	0 Participants	2 Participants	—

SECONDARY outcome

Timeframe: From Week 4 up to Week 16

Population: ITT Population.

The percentage of seizure-free days was calculated as: (total number of days without seizures in the MP / number of applicable days in the MP) \* 100. A seizure-free day is defined as a day with non-missing seizure data but without any seizures. A participant was considered to be seizure free during the MP if he/she had no record of countable seizures of any type, no IS, and no SE during the MP. Participants who had one or more days on which they recorded seizures as "Not Done" on the seizure calendar were not disqualified from being considered as seizure free for that day.

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Percentage of Seizure-free Days in the MP	70.6 Percentage of seizure-free days Standard Deviation 31.55	61.7 Percentage of seizure-free days Standard Deviation 28.31	63.3 Percentage of seizure-free days Standard Deviation 28.45	—

SECONDARY outcome

Timeframe: From Baseline up to Week 16

Population: ITT Population.

The percentage of seizure-free days was calculated as: (total number of days without seizures in the TrP (TiP plus MP) / number of applicable days in the TrP) \* 100. A seizure-free day is defined as a day with non-missing seizure data but without any seizures. A participant was considered to be seizure free during the TrP if he/she had no record of countable seizures of any type, no IS, and no SE during the TrP. Participants who had one or more days on which they recorded seizures as "Not Done" on the seizure calendar were not disqualified from being considered as seizure free for that day.

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Percentage of Seizure-free Days in the TrP	70.4 Percentage of seizure-free days Standard Deviation 31.42	62.1 Percentage of seizure-free days Standard Deviation 27.85	64.9 Percentage of seizure-free days Standard Deviation 27.47	—

SECONDARY outcome

Timeframe: From Baseline up to Week 16

Population: ITT Population.

A participant was considered to have new seizure types during the TrP if they experienced a new seizure types (such as SE, myoclonic, absence, secondary generalization) and had no prior history of these seizure types. At Screening, a history of previous seizure types was collected, with "Yes," "No," "IS," "SE," or "Unknown" being recorded for each of the seizures types. The history of seizure types was updated during the 8-week BP as pre-treatment status. New types of seizures during the TrP were recorded as A1=simple PS with motor signs; AX=simple PS without motor signs; B=complex PS; C=PS evolving to secondary generalized seizures; D1=absence of seizures; D2=myoclonic seizures; D3=clonic seizures; D4=tonic seizures; D5=tonic-clonic seizures; D6=atonic seizures; E=unclassified seizures; and SE=status epilepticus.

Outcome measures

Outcome measures
Measure	Retigabine 600 mg/Day n=26 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 Participants Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day n=24 Participants Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 900 mg/Day Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Simple partial seizures without motor signs	0 Number of events	0 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Absence seizures	0 Number of events	0 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Myoclonic seizures	0 Number of events	0 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Clonic seizures	0 Number of events	0 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Tonic seizures	0 Number of events	0 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Tonic-clonic seizures	0 Number of events	0 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Atonic seizures	0 Number of events	0 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Unclassified seizures	0 Number of events	0 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Status Epilepticus	0 Number of events	0 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Simple partial seizures (sz)with motor signs	0 Number of events	2 Number of events	0 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Partial sz evolving to secondary generalized sz	0 Number of events	0 Number of events	2 Number of events	—
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline Complex partial seizures	1 Number of events	0 Number of events	0 Number of events	—

Adverse Events

Retigabine 900 mg/Day

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Retigabine 600 mg/Day

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Retigabine 900 mg/Day n=24 participants at risk Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Retigabine 600 mg/Day n=26 participants at risk Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.	Placebo n=25 participants at risk Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Nervous system disorders Dizziness	0.00% 0/24 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	3.8% 1/26 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/25 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Nervous system disorders Grand mal convulsion	4.2% 1/24 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/26 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/25 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Pneumonia	0.00% 0/24 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/26 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	4.0% 1/25 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Procedural vomiting	4.2% 1/24 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/26 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/25 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.
Renal and urinary disorders Nephrolithiasis	4.2% 1/24 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/26 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/25 • Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20). SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication.

Other adverse events

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