Retigabine Efficacy and Safety Trial for Partial Onset Re... | NCT00235755

Status Module

Name	Class
Bausch Health Americas, Inc.	INDUSTRY

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Intervention Names
Placebo	Placebo Comparator	Drug: Placebo
Retigabine 600 mg	Experimental	Drug: Retigabine
Retigabine 900 mg	Experimental	Drug: Retigabine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Retigabine	Drug	Oral tablet. The starting daily dose will be 300 mg/day administered orally in three equally divided doses. This dosage will be increased by 150 mg/day (50 mg/dose) at 1-week intervals (titration phase). At the beginning of Week 3, patients will enter a 12 week maintenance phase.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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)	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.	Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)
Number of Participants Classified as Responders and Non-responders During 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.	Week 5 through Week 16

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Who Were Responders and Non-responders During the DB Phase	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.	Week 1 through Week 16

Eligibility Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mid-Atlantic Epilepsy and Sleep Center		Bethesda	Maryland	20817	United States
Neurological Clinic-Texas

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
20944074	Background	Brodie MJ, Lerche H, Gil-Nagel A, Elger C, Hall S, Shin P, Nohria V, Mansbach H; RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology. 2010 Nov 16;75(20):1817-24. doi: 10.1212/WNL.0b013e3181fd6170. Epub 2010 Oct 13.
23342983	Background

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
VRX-RET-E22-302	Study Protocol	View IPD

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo - Double Blind (DB) Phase (Titration Plus Maintenance)	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
BG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
BG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	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
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Baseline characteristics are summarized for the Safety Population, comprised of all participants who were randomized and received at least one dose of study medication.

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00037.7± 11.75 BG00137.5± 12.02 BG00237.7± 12.77 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00090 BG001105 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Caucasian

Title	Measurements
	BG000169 BG001173 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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)

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.

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.

Posted

Median

Full Range

percent change in seizure frequency

Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)

ID	Title	Description
OG000	Placebo - Double Blind (DB) Phase (Titration Plus Maintenance)	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
OG001	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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

Units	Counts
Participants	OG000176 OG001175 OG002179

Title

Denominators

Categories

Title	Measurements
	OG000-15.9(-100 to 1712) OG001-39.9(-100 to 226) OG002-27.9(-94 to 250)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Non-parametric rank ANCOVA		<0.001	Non-parametric rank analysis of covariance adjusted for baseline 28-seizure frequency and stratified by baseline seizure frequency category and region						95							Superiority or Other
OG000 OG002		Non-parametric rank ANCOVA

Primary

Number of Participants Classified as Responders and Non-responders During 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.

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.

Posted

Number

participants

Week 5 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance

Secondary

Number of Participants Who Were Responders and Non-responders During the DB Phase

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.

ITT FDA Population

Posted

Number

participants

Week 1 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase

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.

ITT EMEA Population

Posted

Median

Full Range

Percent change in seizure frequency

Baseline (Week -7 through Week 0), Week 5 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

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

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.

ITT FDA Population

Posted

Number

participants

Baseline (Week -7 through Week 0), Week 1 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

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

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.

ITT FDA Population

Posted

Number

participants

Baseline (Week -7 through Week 0), Week 1 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase

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).

ITT EMEA Population

Posted

Number

participants

Baseline (Week -7 through Week 0), Week 5 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)

Secondary

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

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.

ITT EMEA Population

Posted

Number

participants

Baseline (Week -7 through Week 0), Week 5 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)

Secondary

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

New seizure types included those seizures which were not reported by any participant at Baseline.

ITT FDA Population

Posted

Number

participants

Baseline (Week -7 through Week 0), Week 1 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)

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.

ITT FDA Population. Only participants with post-baseline seizure data were included in the analysis.

Posted

Number

participants

Week 1 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

Number of Participants Who Were Seizure-free During the Maintenance Phase

Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase.

ITT EMEA Population

Posted

Number

participants

Week 5 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)

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%.

ITT FDA Population. Only participants who had post-baseline seizure data were included in the analysis.

Posted

Median

Full Range

percentage of days

Week 1 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

Percentage of Seizure-free Days During the Maintenance Phase

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%.

ITT EMEA Population

Posted

Median

Full Range

percentage of days

Week 5 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase

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.

ITT EMEA Population

Posted

Mean

Standard Deviation

scores on a scale

Week 16/end of treatment phase

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)

Secondary

Patient Global Impression (PGI) Score at the End of the Maintenance Phase

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.

ITT EMEA Population. Only participants with post-baseline PGI scores were included in the analysis.

Posted

Mean

Standard Deviation

scores on a scale

Week 16/end of treatment phase

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002

Secondary

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

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.

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.

Posted

Mean

Standard Deviation

scores on a scale

End of Baseline (Week 0), Weeks 4, 8, and 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)

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.

Safety Population

Posted

Number

participants

Week 1 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)

Secondary

Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)

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.

Safety Population

Posted

Number

participants

Week 1 through Week 16

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	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

Secondary

Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase

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.

Safety Population. Only participants who remained in the study at the indicated week and who also had a PVR assessment were analyzed.

Posted

Median

Full Range

milliliters

Baseline (Week -7 through 0), Weeks 8 and 16

ID	Title	Description
OG000	Placebo: Maintenance Phase	Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID during the 12-week Maintenance Phase
OG001	Retigabine 200 mg TID: Maintenance Phase	Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 200 mg TID during the 12-week Maintenance Phase
OG002	Retigabine 300 mg TID: Maintenance Phase

Secondary

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

The number of participants with recorded weight gain of >=7% over their baseline weight was measured.

Safety Population. Only participants who remained in the study at the indicated week and who also had a body weight assessment were analyzed.

Posted

Number

participants

Weeks 2 and 4 of Titration Phase and Weeks 6, 8, 12, and 16 of Maintenance Phase

ID	Title	Description
OG000	Placebo - DB Phase (Titration Plus Maintenance)	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
OG001	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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
OG002	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo - Double Blind (DB) Phase (Titration Plus Maintenance)	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	7	179	56	179
EG001	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	2	147	38	147
EG002	Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	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	14	181	92	181
EG003	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	3	132	18	132
EG004	Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	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	15	178	117	178
EG005	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	3	114	29	114

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected179 at risk EG0010 affected147 at risk EG0023 affected181 at risk EG0032 affected132 at risk EG0043 affected178 at risk EG0051 affected114 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Coordination abnormal	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Status epilepticus	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Myoclonus	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Nerve root compression	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Atonic urinary bladder	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Sudden unexplained death in epilepsy	General disorders	MedDRA	Systematic Assessment	EG0001 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Gait disturbance	General disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected179 at risk EG0011 affected147 at risk EG0020 affected181 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Psychotic disorder	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0011 affected147 at risk EG0020 affected181 at risk EG003
Acute psychosis	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Deja vu	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Mood disorder due to a general medical condition	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Erysipelas	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Corneal erosion	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Visual disturbance	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0002 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0011 affected147 at risk EG0020 affected181 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Drug toxicity	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0022 affected181 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0020 affected181 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0010 affected147 at risk EG0021 affected181 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG00012 affected179 at risk EG00116 affected147 at risk EG00231 affected181 at risk EG0033 affected132 at risk EG00446 affected178 at risk EG00510 affected114 at risk
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG00018 affected179 at risk EG0019 affected147 at risk EG00226 affected181 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00026 affected179 at risk EG0018 affected147 at risk EG00220 affected181 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0005 affected179 at risk EG0012 affected147 at risk EG00230 affected181 at risk EG003
Tremor	Nervous system disorders	MedDRA	Systematic Assessment	EG0004 affected179 at risk EG0012 affected147 at risk EG0023 affected181 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0005 affected179 at risk EG0011 affected147 at risk EG00215 affected181 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0007 affected179 at risk EG0012 affected147 at risk EG00211 affected181 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0004 affected179 at risk EG0012 affected147 at risk EG0029 affected181 at risk EG003
Memory impairment	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected179 at risk EG0012 affected147 at risk EG0027 affected181 at risk EG003
Diplopia	Eye disorders	MedDRA	Systematic Assessment	EG0002 affected179 at risk EG0011 affected147 at risk EG00212 affected181 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA	Systematic Assessment	EG0004 affected179 at risk EG0012 affected147 at risk EG00213 affected181 at risk EG003
Vision blurred	Eye disorders	MedDRA	Systematic Assessment	EG0003 affected179 at risk EG0012 affected147 at risk EG0021 affected181 at risk EG003
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected179 at risk EG0011 affected147 at risk EG0023 affected181 at risk EG003
Coordination abnormal	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected179 at risk EG0013 affected147 at risk EG00211 affected181 at risk EG003
Gait disturbance	General disorders	MedDRA	Systematic Assessment	EG0001 affected179 at risk EG0011 affected147 at risk EG0026 affected181 at risk EG003

Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 300 mg TID during the Titration Phase, during which participants were titrated from 300 mg per day to 900 mg per day with weekly increases in doses of 150 mg per day over the course of 2 to 4 weeks, followed by a 12-week Maintenance Phase, during which participants were administered 300 mg TID

Retigabine 50 mg and 100 mg tablets were administered orally for a target dose of 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

ID	Term
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D001927	Brain Diseases
D002493	Central Nervous System Diseases