Trial Outcomes & Findings for Safety/Efficacy Study of Retigabine vs. Placebo in Post-Herpetic Neuralgia (PHN) (NCT NCT00612105)

Results Overview

Change from Baseline (BL) was calculated as the value of the average diary pain score for the last 7 days of the MP minus the value of the average pain score at BL (post wash-out period, including the average of the last 7 available entries prior to/including the diary pain measurement on Titration Day 0). Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point Numerical Rating Scale (NRS): 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

187 participants

Primary outcome timeframe

Baseline and Week 4 (Maintenance Phase-MP)

Results posted on

2018-05-08

Participant Flow

Participant milestones

Participant milestones
Measure	1: Retigabine Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Period Title 1: 6-Week Titration Phase STARTED	125	62
Period Title 1: 6-Week Titration Phase COMPLETED	89	57
Period Title 1: 6-Week Titration Phase NOT COMPLETED	36	5
Period Title 2: 4-Week Maintenance Phase STARTED	89	57
Period Title 2: 4-Week Maintenance Phase COMPLETED	78	55
Period Title 2: 4-Week Maintenance Phase NOT COMPLETED	11	2
Period Title 3: 3-Week Taper Phase STARTED	86	58
Period Title 3: 3-Week Taper Phase COMPLETED	85	58
Period Title 3: 3-Week Taper Phase NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	1: Retigabine Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Period Title 1: 6-Week Titration Phase Adverse Event	18	1
Period Title 1: 6-Week Titration Phase Withdrawal by Subject	6	1
Period Title 1: 6-Week Titration Phase Lost to Follow-up	2	0
Period Title 1: 6-Week Titration Phase Physician Decision	1	1
Period Title 1: 6-Week Titration Phase Protocol Violation	1	0
Period Title 1: 6-Week Titration Phase Missed study drug for more than two days	3	1
Period Title 1: 6-Week Titration Phase Lack of Efficacy	5	0
Period Title 1: 6-Week Titration Phase Other	0	1
Period Title 2: 4-Week Maintenance Phase Adverse Event	9	1
Period Title 2: 4-Week Maintenance Phase Missed study drug for more than two days	1	1
Period Title 2: 4-Week Maintenance Phase Lost to Follow-up	1	0
Period Title 3: 3-Week Taper Phase Other	1	0

Baseline Characteristics

Safety/Efficacy Study of Retigabine vs. Placebo in Post-Herpetic Neuralgia (PHN)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1: Retigabine n=125 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=62 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.	Total n=187 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	64 Participants n=5 Participants	34 Participants n=7 Participants	98 Participants n=5 Participants
Age, Categorical >=65 years	61 Participants n=5 Participants	28 Participants n=7 Participants	89 Participants n=5 Participants
Age, Continuous	63.2 years STANDARD_DEVIATION 11.07 • n=5 Participants	61.2 years STANDARD_DEVIATION 14.28 • n=7 Participants	62.5 years STANDARD_DEVIATION 12.23 • n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	36 Participants n=7 Participants	100 Participants n=5 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	26 Participants n=7 Participants	87 Participants n=5 Participants
Region of Enrollment United States	94 participants n=5 Participants	47 participants n=7 Participants	141 participants n=5 Participants
Region of Enrollment South Africa	31 participants n=5 Participants	15 participants n=7 Participants	46 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4 (Maintenance Phase-MP)

Population: Per Protocol (PP) Population: all randomized participants who completed the Titration Phase, had at least 1 dose of treatment in the MP, had at least 3 diary entries in the MP, and did not have any protocol violations or any major protocol deviations

Change from Baseline (BL) was calculated as the value of the average diary pain score for the last 7 days of the MP minus the value of the average pain score at BL (post wash-out period, including the average of the last 7 available entries prior to/including the diary pain measurement on Titration Day 0). Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point Numerical Rating Scale (NRS): 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.

Outcome measures

Outcome measures
Measure	1: Retigabine n=81 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=51 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Primary Endpoint Will be the Change From Baseline in Average Pain Score Over the Last 7 Days of the Maintenance Phase.	-2.65 Scores on a scale Standard Error 0.354	-2.22 Scores on a scale Standard Error 0.387

SECONDARY outcome

Timeframe: Baseline and Weeks 2 and 4 (Maintenance Phase - MP)

Population: Intent-to-Treat (ITT) Population: all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy assessment. All participants providing data for the measure are included in the analysis. Differences from the overall population numbers are due to missing data or to subjects missing visits.

Participants rated their pain during the previous 24 hours at all clinic visits using an 11-point Numerical Rating Scale (NRS): 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain (10=worst possible pain). Change in In-clinic Pain Assessment was calculated by subtracting the average score on the NRS at Week 2 and Week 4 (values for each week were observed cases) of the MP from the average score on the NRS at Baseline (the last non-missing measurement prior to taking study drug).

Outcome measures

Outcome measures
Measure	1: Retigabine n=88 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Change From Baseline to Weeks 2 and 4 of the Maintenance Phase in Mean In-clinic Pain Assessment Category Title 1:Week 2; n=88, 57	-2.7 Scores on a scale Standard Deviation 2.51	-2.4 Scores on a scale Standard Deviation 2.18
Change From Baseline to Weeks 2 and 4 of the Maintenance Phase in Mean In-clinic Pain Assessment Category Title 2: Week 4, n=82, 56	-2.9 Scores on a scale Standard Deviation 2.41	-2.4 Scores on a scale Standard Deviation 2.14

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, and 4 Maintenance Phase

Population: ITT Population. All participants providing data for the measure are included in the analysis. Differences from the overall population numbers are due to missing data or to subjects missing visits.

Participants recorded the number of acetaminophen tablets taken during the previous 24 hours in a participant diary. Rescue medication was summarized as the mean number of doses taken per day during each week of the Maintenance Phase (MP) and the mean number of doses taken during all MP weeks.

Outcome measures

Outcome measures
Measure	1: Retigabine n=88 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Rescue Medication Tablets Taken Per Day During the Maintenance Phase (MP) Category Title 2: Week 2; n=86, 56	0.89 Tablets/Day Standard Deviation 1.228	0.79 Tablets/Day Standard Deviation 1.158
Number of Rescue Medication Tablets Taken Per Day During the Maintenance Phase (MP) Category Title 1: Week 1; n=88, 57	0.92 Tablets/Day Standard Deviation 1.357	0.84 Tablets/Day Standard Deviation 1.239
Number of Rescue Medication Tablets Taken Per Day During the Maintenance Phase (MP) Category Title 3: Week 3; n=82, 56	0.74 Tablets/Day Standard Deviation 1.174	0.85 Tablets/Day Standard Deviation 1.254
Number of Rescue Medication Tablets Taken Per Day During the Maintenance Phase (MP) Category Title 4: Week 4; n=76, 55	0.83 Tablets/Day Standard Deviation 1.340	0.77 Tablets/Day Standard Deviation 1.218
Number of Rescue Medication Tablets Taken Per Day During the Maintenance Phase (MP) Category Title 5: All Maintenance Phase Weeks; n=8	0.87 Tablets/Day Standard Deviation 1.211	0.83 Tablets/Day Standard Deviation 1.193

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, and 4 (MP)

Population: ITT Population. All participants providing data for the measure are included in the analysis. Differences from the overall population numbers are due to missing data or to subjects missing visits.

Least square mean (LSM) of pain intensity was calculated from the NRS score entered by the participants in their diaries at each week during the MP. Participants rated their pain during the previous 24 hours at all clinic visits using an NRS: 0, no pain; 1-3, mild; 4-6, moderate; 7-10 (worst possible pain), severe pain. Change from Baseline was calculated by subtracting the value of the average of the LSM of the NRS score at each week during the MP (the last 7 available diary entries in the MP were used, provided at least 3 existed) from the average Baseline value of the LSM of the NRS score.

Outcome measures

Outcome measures
Measure	1: Retigabine n=88 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Change From Baseline in Pain Intensity Score at Each Week During the Maintenance Phase (MP) Category Title 1: Week 1; n=88, 57	-2.35 Scores on a scale Standard Deviation 0.323	-2.08 Scores on a scale Standard Deviation 0.356
Change From Baseline in Pain Intensity Score at Each Week During the Maintenance Phase (MP) Category Title 2: Week 2; n=86, 56	-2.64 Scores on a scale Standard Deviation 0.337	-2.34 Scores on a scale Standard Deviation 0.372
Change From Baseline in Pain Intensity Score at Each Week During the Maintenance Phase (MP) Category Title 3: Week 3; n=78, 56	-2.82 Scores on a scale Standard Deviation 0.335	-2.43 Scores on a scale Standard Deviation 0.363
Change From Baseline in Pain Intensity Score at Each Week During the Maintenance Phase (MP) Category Title 4: Week 4; n=75, 55	-2.82 Scores on a scale Standard Deviation 0.320	-2.47 Scores on a scale Standard Deviation 0.348

SECONDARY outcome

Timeframe: Baseline and Week 4 Maintenance Phase (MP)

Population: ITT Population. All participants providing data for this analysis had to have 7 available baseline diary entries.

Responders were defined as participants achieving a mean \>=50% or \>=30% pain reduction based on the NRS score from Baseline to the last 7 days of the MP. Those participants who did not have at least 3 diary entries in the MP, those who withdrew during the Titration Phase (TP), and non-completers (NC: who did not complete the study) were classified as non-responders. The number of responders and responders including non-completers from Baseline to the last 7 days of the MP were reported.

Outcome measures

Outcome measures
Measure	1: Retigabine n=123 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=61 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Participants Classified as Responders, With a 50% and 30% Pain Reduction From Baseline to the Last 7 Days of the Maintenance Phase Responders with>=50% Pain Reduction	33 Participants	22 Participants
Number of Participants Classified as Responders, With a 50% and 30% Pain Reduction From Baseline to the Last 7 Days of the Maintenance Phase Responders with >=30% Pain Reduction	52 Participants	32 Participants
Number of Participants Classified as Responders, With a 50% and 30% Pain Reduction From Baseline to the Last 7 Days of the Maintenance Phase Responders plus NC with>=50% Pain Reduction	33 Participants	22 Participants
Number of Participants Classified as Responders, With a 50% and 30% Pain Reduction From Baseline to the Last 7 Days of the Maintenance Phase Responders plus NC with>=30% Pain Reduction	49 Participants	31 Participants

SECONDARY outcome

Timeframe: Baseline and End of Maintenance Phase (MP) (Week 4).

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP.

Change from BL (average value of MOS Sleep Scale score including Overall Sleep Problem \[OSP\] Index at end of MP minus average BL value) to the end of the MP was summarized for the OSP Index, in addition to the following subscales of the MOS Sleep Scale: Sleep Disturbance; Sleep Adequacy; Snoring; Awakening with Shortness of Breath or with a Headache; Somnolence; and Optimal Sleep. Each item was transformed to a scale with a range of 0-100. For each subscale, except Optimal Sleep, higher scores indicate a greater level of what was being measured (i.e., more snoring, more sleep adequacy, etc.).

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Change From Baseline to the End of the MP (Included All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP) in Medical Outcomes Study (MOS) Sleep Scale Scores Category Title 1: Overall Sleep Problem Index	-5.70 Scores on a scale Standard Deviation 15.969	-6.88 Scores on a scale Standard Deviation 16.814
Change From Baseline to the End of the MP (Included All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP) in Medical Outcomes Study (MOS) Sleep Scale Scores Category Title 2: Sleep Disturbance	-11.47 Scores on a scale Standard Deviation 21.802	-9.43 Scores on a scale Standard Deviation 22.537
Change From Baseline to the End of the MP (Included All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP) in Medical Outcomes Study (MOS) Sleep Scale Scores Category Title 3: Sleep Adequacy	9.05 Scores on a scale Standard Deviation 25.536	5.26 Scores on a scale Standard Deviation 26.599
Change From Baseline to the End of the MP (Included All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP) in Medical Outcomes Study (MOS) Sleep Scale Scores Category Title 4: Snoring	0.7 Scores on a scale Standard Deviation 23.12	-2.5 Scores on a scale Standard Deviation 21.07
Change From Baseline to the End of the MP (Included All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP) in Medical Outcomes Study (MOS) Sleep Scale Scores Title 4:Awaken Short of Breath or with a Headache	-4.8 Scores on a scale Standard Deviation 19.54	-4.6 Scores on a scale Standard Deviation 22.68
Change From Baseline to the End of the MP (Included All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP) in Medical Outcomes Study (MOS) Sleep Scale Scores Category Title 6: Somnolence	8.10 Scores on a scale Standard Deviation 20.777	-3.39 Scores on a scale Standard Deviation 18.349

SECONDARY outcome

Timeframe: Baseline and End of Maintenance Phase (MP) (Week 4).

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP.

Change from Baseline in sleep quantity was calculated by subtracting the average value of sleep quantity, calculated in hours, at the end of the MP from the average Baseline value.

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Change From Baseline to the End of the MP (Included All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP) in Sleep Quantity	0.5 Hours Standard Deviation 1.73	0.2 Hours Standard Deviation 1.07

SECONDARY outcome

Timeframe: Baseline and End of Maintenance Phase (MP) (Week 4).

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP.

Optimal Sleep was based on the Sleep Quantity domain of the MOS Sleep Scale and included the options of "Yes" if sleep quantity was 7-8 hours, and "No" otherwise. "Improved" indicated a change in response of no at baseline to yes at the end of the MP, "Same" indicated no change in response, and "Worse" indicated a change in response from yes at baseline to no at the end of the MP.

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Participants With the Indicated Change From Baseline to the End of the Maintenance Phase in Optimal Sleep Based on the Sleep Quantity Domain of the MOS Sleep Scale Category Title 1: Improved	12 Participants	8 Participants
Number of Participants With the Indicated Change From Baseline to the End of the Maintenance Phase in Optimal Sleep Based on the Sleep Quantity Domain of the MOS Sleep Scale Category Title 2: Same	63 Participants	42 Participants
Number of Participants With the Indicated Change From Baseline to the End of the Maintenance Phase in Optimal Sleep Based on the Sleep Quantity Domain of the MOS Sleep Scale Category Title 3: Worse	9 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline to the end of Maintenance Phase (MP) (Week 4)

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP.

For the PGIC assessment, participants were asked to assess their overall status since they initiated the study drug to the end of the Maintenance Phase using a 7-point categorical scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. All participants who completed Week 4 of the Maintenance Phase and participants who terminated early during the Maintenance Phase were assessed.

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Participants With the Indicated Overall Patient Global Impression of Change (PGIC) Category Title 1: Very Much Improved	20 Participants	8 Participants
Number of Participants With the Indicated Overall Patient Global Impression of Change (PGIC) Category Title 2: Much Improved	27 Participants	15 Participants
Number of Participants With the Indicated Overall Patient Global Impression of Change (PGIC) Category Title 3: Minimally Improved	19 Participants	10 Participants
Number of Participants With the Indicated Overall Patient Global Impression of Change (PGIC) Category Title 4: No Change	14 Participants	21 Participants
Number of Participants With the Indicated Overall Patient Global Impression of Change (PGIC) Category Title 5: Minimally Worse	3 Participants	2 Participants
Number of Participants With the Indicated Overall Patient Global Impression of Change (PGIC) Category Title 6: Much Worse	1 Participants	1 Participants
Number of Participants With the Indicated Overall Patient Global Impression of Change (PGIC) Category Title 7: Very Much Worse	0 Participants	0 Participants

SECONDARY outcome

Timeframe: End of Maintenance Phase (MP) (Week 4)

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP. Differences from the overall population numbers are due to missing data or to participants missing visits.

The TSQM assessed the participant's overall satisfaction with treatment, including subscales to assess effectiveness, side effects, convenience, and global satisfaction. Raw scores from the scale were transformed into a numeric scale ranging from 0 to 100, where higher scores indicated greater satisfaction with treatment. TSQM was reported at the end of the MP. Participants who completed Week 4 of the MP and who terminated early during the MP were assessed.

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Mean Score on the Treatment Satisfaction Questionnaire for Medication (TSQM) at the End of the Maintenance Phase Category Title 1: Effectiveness; n=83, 57	59.10 Scores on a scale Standard Deviation 29.392	49.51 Scores on a scale Standard Deviation 30.143
Mean Score on the Treatment Satisfaction Questionnaire for Medication (TSQM) at the End of the Maintenance Phase Category Title 2: Side Effects; n=82, 57	67.76 Scores on a scale Standard Deviation 28.097	92.11 Scores on a scale Standard Deviation 18.280
Mean Score on the Treatment Satisfaction Questionnaire for Medication (TSQM) at the End of the Maintenance Phase Category Title 3: Convenience; n=84, 57	69.97 Scores on a scale Standard Deviation 21.423	74.66 Scores on a scale Standard Deviation 19.782
Mean Score on the Treatment Satisfaction Questionnaire for Medication (TSQM) at the End of the Maintenance Phase Category Title 4: Global Satisfaction; n=84, 57	58.67 Scores on a scale Standard Deviation 30.649	52.88 Scores on a scale Standard Deviation 34.517

SECONDARY outcome

Timeframe: End of Maintenance Phase (MP) (Week 4)

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP. Differences from the overall population numbers are due to missing data or to participants missing visits.

The BPI-SF assessed pain intensity, pain relief from medication, and pain interference with function over the previous 24 hours. Pain intensity was assessed by the mean of 4 intensity items rated on a 0-10 categorical scale: 0=no pain, 10=pain as bad as you can imagine. Pain interference was assessed by determining the mean of the 7 interference items on a 0-10 categorical scale ranging from 0=does not interfere to 10=completely interferes. The level of pain relief provided by treatment was assessed on an 11-point categorical scale ranging from 0% to 100%

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Scores on the Brief Pain Inventory-Short Form (BPI-SF) at the End of the MP for All Participants Who Completed Week-4 of the MP and Who Terminated Early During the MP Category Title 1: Pain Intensity; n=74, 49	3.17 Scores on a scale Standard Deviation 2.092	3.58 Scores on a scale Standard Deviation 2.299
Scores on the Brief Pain Inventory-Short Form (BPI-SF) at the End of the MP for All Participants Who Completed Week-4 of the MP and Who Terminated Early During the MP Category Title 2: Pain Interference; n=75, 49	2.00 Scores on a scale Standard Deviation 2.159	2.27 Scores on a scale Standard Deviation 2.147
Scores on the Brief Pain Inventory-Short Form (BPI-SF) at the End of the MP for All Participants Who Completed Week-4 of the MP and Who Terminated Early During the MP Category Title 3: Pain Relief; n=74, 48	58.4 Scores on a scale Standard Deviation 35.04	49.4 Scores on a scale Standard Deviation 36.17

SECONDARY outcome

Timeframe: End of Maintenance Phase (MP) (Week 4)

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP. Differences from the overall population numbers are due to missing data or to participants missing visits.

Least square (LS) mean calculated based on participant's assessment of SF-36,a quality of life questionnaire consisting of 36 items grouped into 8 domains. These 8 domains further grouped into 2 overall summary measures,physical health and mental health. Higher scores on SF-36 represented better state of health. Physical/mental components summarized the data of all the physical/mental domains of SF-36 and higher scores represented better state of health.

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=55 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP Category Title 6: Bodily Pain; n=84, 55	47.23 Scores on a scale Standard Error 0.883	45.60 Scores on a scale Standard Error 1.091
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP Category Title 1: General health; n=83, 55	51.12 Scores on a scale Standard Error 0.816	50.47 Scores on a scale Standard Error 1.002
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP Category Title 2: Physical Functioning; n=84, 55	43.82 Scores on a scale Standard Error 0.870	45.54 Scores on a scale Standard Error 1.076
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP Category Title3: Role limitations, physical; n=84,	43.22 Scores on a scale Standard Error 1.046	43.30 Scores on a scale Standard Error 1.293
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP Category Title4: Role limitations, emotional; n=84	44.31 Scores on a scale Standard Error 1.226	42.68 Scores on a scale Standard Error 1.517
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP tegory Title 5: Social Functioning; n=84, 55	50.14 Scores on a scale Standard Error 0.858	50.25 Scores on a scale Standard Error 1.061
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP Category Title 7: Vitality; n=84, 55	51.68 Scores on a scale Standard Error 0.904	53.94 Scores on a scale Standard Error 1.117
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP Category Title 8: Mental Health; n=84, 55	51.66 Scores on a scale Standard Error 0.871	51.34 Scores on a scale Standard Error 1.076
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP Category Title9: Physical Component Summary; n=83,	45.26 Scores on a scale Standard Error 0.691	45.65 Scores on a scale Standard Error 0.849
Scores on the Medical Outcomes Short Form-36 (SF-36) at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP Category Title10: Mental Component Summary; n=83,	51.22 Scores on a scale Standard Error 0.944	50.91 Scores on a scale Standard Error 1.160

SECONDARY outcome

Timeframe: End of maintenance Phase (MP) (Week 4)

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP. Differences from the overall population numbers are due to missing data or to participants missing visits.

The least square (LS) mean score for reported health transition was calculated based on the scores (ranging from 1 to 5) given by the participant in answer to the following question: "Compared to 1 year ago, how would you rate your health in general now?". Lower numbers represent a better state of health.

Outcome measures

Outcome measures
Measure	1: Retigabine n=83 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=55 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Scores for Reported Health Transition at the End of the MP for All Participants Who Completed Week 4 of the MP and Who Terminated Early During the MP	2.68 Scores on a scale Standard Error 0.102	2.37 Scores on a scale Standard Error 0.125

SECONDARY outcome

Timeframe: Baseline Phase (Day -7 to Randomization Day 0)

Population: ITT Population - All participants providing data for the measure are included in the analysis. Differences from the overall population numbers are due to missing data or to subjects missing visits.

At Baseline, the investigator conducted the Neuropathic Pain Physical Examination (NPPE) to examine hyperalgesia and allodynia (tactile and cold). Tactile allodynia was assessed with a foam brush, based on the question:"How painful was the affected side compared to the opposite side?".

Outcome measures

Outcome measures
Measure	1: Retigabine n=124 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=61 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Participants With the Indicated Responses at Baseline to the Question: "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Tactile Allodynia Category Title 1: More Painful	89 Participants	40 Participants
Number of Participants With the Indicated Responses at Baseline to the Question: "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Tactile Allodynia Category Title 2: The Same	19 Participants	14 Participants
Number of Participants With the Indicated Responses at Baseline to the Question: "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Tactile Allodynia Category Title 3: Less Painful	16 Participants	7 Participants

SECONDARY outcome

Timeframe: Timeframe: Baseline Phase (Day -7 to Randomization Day 0)

Population: ITT Population - All participants providing data for the measure are included in the analysis. Differences from the overall population numbers are due to missing data or to subjects missing visits.

At Baseline the investigator conducted the NPPE to examine hyperalgesia and allodynia (tactile and cold). Cold threshold and allodynia was assessed to determine if a metal bar felt cool and if it felt painful, based on the questions:"Is it cool?" and "Is it painful?"

Outcome measures

Outcome measures
Measure	1: Retigabine n=124 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=61 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Participants With the Indicated Responses at Baseline to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia Is Not Cool	19 Participants	9 Participants
Number of Participants With the Indicated Responses at Baseline to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia Is Cool	105 Participants	52 Participants
Number of Participants With the Indicated Responses at Baseline to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia Is Not Painful	67 Participants	34 Participants
Number of Participants With the Indicated Responses at Baseline to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia Is Painful	57 Participants	27 Participants

SECONDARY outcome

Timeframe: Baseline Phase (Day -7 to Randomization Day 0)

Population: ITT Population - All participants providing data for the measure are included in the analysis. Differences from the overall population numbers are due to missing data or to subjects missing visits.

At Baseline the investigator conducted the NPPE to examine hyperalgesia and allodynia (tactile and cold). Hyperalgesia is defined as increased sensitivity to pain, which may be caused by damage to peripheral nerves. It was assessed with a pinprick brush, based on the questions: "How sharp was the affected side compared to the opposite side?" and "How painfule was the affected side compared to the opposite side?"

Outcome measures

Outcome measures
Measure	1: Retigabine n=124 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=61 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Subjects With the Indicated Responses at Baseline to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painfule Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia More Sharp	66 Participants	32 Participants
Number of Subjects With the Indicated Responses at Baseline to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painfule Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia The Same(sharp)	7 Participants	10 Participants
Number of Subjects With the Indicated Responses at Baseline to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painfule Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia Less sharp	51 Participants	19 Participants
Number of Subjects With the Indicated Responses at Baseline to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painfule Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia More Painful	71 Participants	38 Participants
Number of Subjects With the Indicated Responses at Baseline to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painfule Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia The Same(pain)	19 Participants	7 Participants
Number of Subjects With the Indicated Responses at Baseline to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painfule Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia Less Painful	34 Participants	16 Participants

SECONDARY outcome

Timeframe: End of Maintenance Phase (MP) (Week 4)

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP.

At the end of the MP, the investigator conducted the NPPE (an examination of the effect of retigabine on sensory abnormalities) to examine hyperalgesia and allodynia (tactile and cold). Tactile allodynia was assessed with a foam brush, based on the question:"How painful was the affected side compared to the opposite side?" End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP.

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Participants With the Indicated Responses at the End of the MP to the Question: "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Tactile Allodynia More Painful	30 Participants	29 Participants
Number of Participants With the Indicated Responses at the End of the MP to the Question: "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Tactile Allodynia The Same	44 Participants	20 Participants
Number of Participants With the Indicated Responses at the End of the MP to the Question: "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Tactile Allodynia Less Painful	10 Participants	8 Participants

SECONDARY outcome

Timeframe: End of Maintenance Phase (MP) (Week 4)

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP.

At the end of the MP, the investigator conducted the NPPE (an examination of the effect of retigabine on sensory abnormalities) to examine hyperalgesia and allodynia (tactile and cold). Cold threshold and allodynia was assessed to determine if a metal bar felt cool and if it felt painful, based on the questions:"Is it cool?" and "Is it painful?"

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Participants With the Indicated Responses at the End of the MP to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia Is Not Cool	14 Participants	7 Participants
Number of Participants With the Indicated Responses at the End of the MP to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia Is Cool	70 Participants	50 Participants
Number of Participants With the Indicated Responses at the End of the MP to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia Is Not Painful	63 Participants	44 Participants
Number of Participants With the Indicated Responses at the End of the MP to the Questions of "Is it Cool?" and "Is it Painful?" in an Assessment of Cold Threshold and Allodynia Is Painful	21 Participants	13 Participants

SECONDARY outcome

Timeframe: End of Maintenance Phase (MP) (Week 4)

Population: ITT Population includes all participants who entered MP and provided data. End of Maintenance Phase includes participants who completed Week 4 of the MP and who terminated early during the MP.

At the end of the MP, the investigator conducted the NPPE (an examination of the effect of retigabine on sensory abnormalities) to examine hyperalgesia and allodynia (tactile and cold). Hyperalgesia is defined as increased sensitivity to pain, which may be caused by damage to peripheral nerves. It was assessed with a pinprick brush, based on the questions:"How sharp was the affected side compared to the opposite side?" and How painful was the affected side compared to the opposite side?"

Outcome measures

Outcome measures
Measure	1: Retigabine n=84 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=57 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Number of Participants With Indicated Responses at the End of the MP to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia More Sharp	29 Participants	24 Participants
Number of Participants With Indicated Responses at the End of the MP to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia The Same(sharp)	24 Participants	19 Participants
Number of Participants With Indicated Responses at the End of the MP to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia Less Sharp	31 Participants	14 Participants
Number of Participants With Indicated Responses at the End of the MP to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia More Painful	31 Participants	24 Participants
Number of Participants With Indicated Responses at the End of the MP to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia The Same(pain)	28 Participants	18 Participants
Number of Participants With Indicated Responses at the End of the MP to the Questions: "How Sharp Was the Affected Side Compared to the Opposite Side?" and "How Painful Was the Affected Side Compared to the Opposite Side?" in an Assessment of Hyperalgesia Less Painful	25 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline and Week 4 Maintenance Phase (MP)

Population: ITT Population. Only participants in the specified subgroup were analyzed.

Participants were stratified into four different PHN subtypes based on the NPPE. Participants with pain, abnormal sensitization of the specific receptor (irritable nociceptors), and with minimal sensory loss were stratified in the"irritable nociceptors" subtype. Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point NRS: 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.

Outcome measures

Outcome measures
Measure	1: Retigabine n=17 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=13 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Change From Baseline in the Average Diary Pain Score to the Last 7 Days of the Maintenance Phase by Post Herpetic Neuralgia (PHN) Subtype "Irritable Nociceptors"	-1.78 Scores on a scale Standard Deviation 2.166	-2.85 Scores on a scale Standard Deviation 2.163

SECONDARY outcome

Timeframe: Baseline and Week 4 Maintenance Phase (MP)

Population: ITT Population. Only participants in the specified subgroup were analyzed.

Participants stratified into 4 different PHN subtypes based on NPPE. Participants with marked sensory loss associated with severe burning pain upon slight mechanical stimuli (allodynia) were stratified in the "deafferentation type 1" subtype. Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point NRS: 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.

Outcome measures

Outcome measures
Measure	1: Retigabine n=4 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=2 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Change From Baseline in the Average Diary Pain Score to the Last 7 Days of the Maintenance Phase by Post Herpetic Neuralgia (PHN) Subtype"Deafferentation Type 1 (D Type 1)"	-3.57 Scores on a scale Standard Deviation 2.368	-5.29 Scores on a scale Standard Deviation 0.000

SECONDARY outcome

Timeframe: Baseline and Week 4 Maintenance phase (MP)

Population: ITT Population. Only participants in the specified subgroup were analyzed.

Participants stratified into 4 different PHN subtypes based on NPPE. Participants with marked sensory loss and severe spontaneous burning pain without allodynia associated with reorganization of central nerve fibers were stratified in the "deafferentation type 2" subtype. Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point NRS: 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.

Outcome measures

Outcome measures
Measure	1: Retigabine n=4 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=2 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Change From Baseline in the Average Diary Pain Score to the Last 7 Days of the Maintenance Phase by Post Herpetic Neuralgia (PHN) Subtype "Deafferentation Type 2 (D Type 2)"	-4.14 Scores on a scale Standard Deviation 0.00	0.00 Scores on a scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: Baseline and Week 4 Maintenance Phase (MP)

Population: ITT Population. Only participants in the specified subgroup were analyzed.

Participants stratified into 4 different PHN subtypes based on NPPE. Participants who could not be specifically differentiated in any of the other three subtypes were stratified as "unclassifiable" meaning that the participants could not be classified into any of the predefined PHN subtypes. Based on their pain experienced during the previous 24 hours, participants assessed their pain every evening at bedtime in an electronic diary by choosing the appropriate number on an 11-point NRS: 0, no pain; 1 to 3, mild; 4 to 6, moderate; 7 to 10, severe pain.

Outcome measures

Outcome measures
Measure	1: Retigabine n=66 Participants Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=42 Participants Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Change From Baseline in the Average Diary Pain Score to the Last 7 Days of the Maintenance Phase by Post Herpetic Neuralgia (PHN) Subtype "Unclassifiable"	-2.69 Scores on a scale Standard Deviation 2.285	-1.87 Scores on a scale Standard Deviation 1.870

Adverse Events

1: Retigabine

Serious events: 7 serious events

Other events: 98 other events

Deaths: 0 deaths

2: Placebo

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1: Retigabine n=125 participants at risk Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=62 participants at risk Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Cardiac disorders Atrial Fibrillation	1.6% 2/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Eye disorders Maculopathy	0.80% 1/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Eye disorders Retinal Detatchment	0.80% 1/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Infections and infestations Pneumonia	1.6% 2/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Infections and infestations Clostridium Difficile Colitis	0.80% 1/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Injury, poisoning and procedural complications Femoral Neck Fracture	0.80% 1/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Injury, poisoning and procedural complications Tibia Fracture	0.80% 1/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Respiratory, thoracic and mediastinal disorders Pulmonaryy Embolism	0.80% 1/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	1.6% 1/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	1.6% 1/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).

Other adverse events

Additional Information

Associate Director Clinical Operations

Valeant Pharmaceuticals International, Inc.

Phone: 919-294-3080

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Valeant 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

Measure	1: Retigabine n=125 participants at risk Arm Description: Participants started on a total daily dose of 150 milligrams (mg) and were titrated to their maximum tolerated dose (MTD) up to a maximum of 900 mg daily using retigabine 50 mg and/or 100 mg tablets. The dose was increased by 150 mg each week and administered 3 times daily (TID) in equally divided doses. In the Maintenance Phase, retigabine was administered in equally divided doses to maintain the participant's MTD. Participants with moderate to severe side effects during the first week at their MTD and who had attained at least dose level 3 (450 mg) were allowed a one level dose reduction (150 mg). Participants unable to maintain the MTD discontinued the medication. In the Taper Phase, the dose was reduced by one-third during each of the first two weeks, and the study medication was stopped by the third week during the 3-week duration.	2: Placebo n=62 participants at risk Arm Description: Matching placebo tablets of dummy strengths of 50 mg and 100 mg were administered orally TID for up to 6 weeks of the Titration Phase, 4 weeks of the Maintenance Phase, and 3 weeks of the Taper Phase.
Nervous system disorders Dizziness	36.0% 45/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	12.9% 8/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Nervous system disorders Somnolence	32.8% 41/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	11.3% 7/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Nervous system disorders Headache	18.4% 23/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	12.9% 8/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Nervous system disorders Memory Impairment	7.2% 9/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Nervous system disorders Amnesia	5.6% 7/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Nervous system disorders Paraesthesia	5.6% 7/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Gastrointestinal disorders Nausea	12.0% 15/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	4.8% 3/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Gastrointestinal disorders Diarrhea	9.6% 12/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	9.7% 6/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Gastrointestinal disorders Dry Mouth	7.2% 9/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	3.2% 2/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Psychiatric disorders Confusional State	7.2% 9/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	1.6% 1/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
General disorders Fatigue	10.4% 13/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Musculoskeletal and connective tissue disorders Back Pain	5.6% 7/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Infections and infestations Urinary Tract Infection	6.4% 8/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	6.5% 4/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Eye disorders Vision Blurred	6.4% 8/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	4.8% 3/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).
Ear and labyrinth disorders Vertigo	6.4% 8/125 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).	0.00% 0/62 SAEs and AEs are reported for all Phases (Titration, Maintenance and Taper).