Trial Outcomes & Findings for Efficacy Study Measuring the Impact of Pregabalin on Peripheral Neuropathic Pain. (NCT NCT00219544)

NCT ID: NCT00219544

Last Updated: 2021-01-22

Results Overview

Pain score end of Double-Blind treatment = mean of last 7 available pain scores from daily pain diary while on Double-Blind treatment. A Daily Pain Rating Score : 11- point numerical scale ranging from 0 ("no pain") to 10 ("worst possible pain").

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 158 participants
• Primary outcome timeframe: 9 weeks
• Results posted on: 2021-01-22

Participant Flow

This study was conducted in Canada.

405 subjects enrolled - 234 completed the single-blind phase. Subjects who responded (≥30% decrease in weekly mean pain score) during single-blind entered double-blind. 158 subjects assigned to study drug in double-blind phase. One subject in placebo group was randomized in error, not treated, not included as discontinuation;157 received treatment.

Participant milestones

Measure	Pregabalin subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Single Blind Treatment Period STARTED	256	0
Single Blind Treatment Period COMPLETED	234	0
Single Blind Treatment Period NOT COMPLETED	22	0
Double Blind Treatment Period STARTED	80	77
Double Blind Treatment Period COMPLETED	80	77
Double Blind Treatment Period NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Pregabalin subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Single Blind Treatment Period Lack of Efficacy	5	0
Single Blind Treatment Period Adverse Event	9	0
Single Blind Treatment Period Protocol Violation	4	0
Single Blind Treatment Period Lost to Follow-up	2	0
Single Blind Treatment Period Investigator decision to withdraw	1	0
Single Blind Treatment Period Withdrawal by Subject	1	0

Baseline Characteristics

Efficacy Study Measuring the Impact of Pregabalin on Peripheral Neuropathic Pain.

Baseline characteristics by cohort

Measure	Pregabalin n=256 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.
Age, Continuous	58.4 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	128 Participants n=5 Participants
Sex: Female, Male Male	128 Participants n=5 Participants

PRIMARY outcome

Timeframe: 9 weeks

Population: Full Analysis Set (FAS) = Intent-to-Treat (ITT) population, defined as all subjects who are randomized into the Double-Blind treatment phase, who receive at least one dose of Double-Blind study medication and complete at least one postrandomization efficacy assessment.

Pain score end of Double-Blind treatment = mean of last 7 available pain scores from daily pain diary while on Double-Blind treatment. A Daily Pain Rating Score : 11- point numerical scale ranging from 0 ("no pain") to 10 ("worst possible pain").

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=75 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Neuropathic Pain in Subjects With Peripheral Neuropathic Pain Conditions During the Double-blind Phase	2.84 score on scale Standard Error 0.18	3.62 score on scale Standard Error 0.18

SECONDARY outcome

Timeframe: 0 and 4 weeks

Population: Full Analysis Set (FAS)

Pain score at Week 0 and Week 4, end of single-bind treatment. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11- point numerical scale ranging from 0 ("no pain") to 10 ("worst possible pain").

Outcome measures

Measure	Pregabalin n=255 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Weekly Mean Pain Scores During the Single-blind Treatment Phase Week 0 - Baseline	6.29 score on scale Standard Deviation 1.43	—
Weekly Mean Pain Scores During the Single-blind Treatment Phase Week 4 - end of single-blind treatment	3.79 score on scale Standard Deviation 2.11	—

SECONDARY outcome

Timeframe: Week 4 - 9

Population: FAS population.

Mean Pain scores for weeks 4, 5, 6, 7, 8 and 9. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 ("no pain") to 10 ("worst possible pain").

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=75 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Weekly Mean Pain Scores During the Double Blind Treatment Phase Week 4 (n=73, 70)	2.68 score on scale Standard Deviation 1.29	2.49 score on scale Standard Deviation 1.23
Weekly Mean Pain Scores During the Double Blind Treatment Phase Week 5 (n=70,64)	2.62 score on scale Standard Deviation 1.48	3.14 score on scale Standard Deviation 1.41
Weekly Mean Pain Scores During the Double Blind Treatment Phase Week 6 (n=66,63)	2.75 score on scale Standard Deviation 1.76	3.40 score on scale Standard Deviation 1.49
Weekly Mean Pain Scores During the Double Blind Treatment Phase Week 7 (n=60,56)	2.53 score on scale Standard Deviation 1.80	3.20 score on scale Standard Deviation 1.45
Weekly Mean Pain Scores During the Double Blind Treatment Phase Week 8 (n=63,53)	2.51 score on scale Standard Deviation 1.59	3.16 score on scale Standard Deviation 1.54
Weekly Mean Pain Scores During the Double Blind Treatment Phase Week 9 (n=67,58)	2.80 score on scale Standard Deviation 1.80	3.29 score on scale Standard Deviation 1.52

SECONDARY outcome

Timeframe: 9 weeks

Population: Full Analysis Set (FAS)

Change in Mean Pain score = Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 ("no pain") to 10 ("worst possible pain").

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=75 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Change in Pain Scores During Double Blind Treatment Phase Change from randomization to Week 5 (n=70, 64)	-0.01 score on scale Standard Error 0.15	0.71 score on scale Standard Error 0.16
Change in Pain Scores During Double Blind Treatment Phase Change from randomization to Week 6 (n=66, 63)	0.08 score on scale Standard Error 0.16	1.05 score on scale Standard Error 0.16
Change in Pain Scores During Double Blind Treatment Phase Change from randomization to Week 7 (n=60, 56)	-0.06 score on scale Standard Error 0.16	0.87 score on scale Standard Error 0.17
Change in Pain Scores During Double Blind Treatment Phase Change from randomization to Week 8 (n=63,53)	-0.10 score on scale Standard Error 0.16	0.83 score on scale Standard Error 0.17
Change in Pain Scores During Double Blind Treatment Phase Change from randomization to Week 9 (n=67,58)	0.14 score on scale Standard Error 0.15	0.84 score on scale Standard Error 0.17

SECONDARY outcome

Timeframe: Week 4 (end of single-blind treatment phase)

Population: 256 subjects entered the single-blind treatment phase, one subject did not have enough DPRS assessments for calculation.

Responders = ≥30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 ("no pain") to 10 ("worst possible pain").

Outcome measures

Measure	Pregabalin n=255 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Number of Subjects With >= 30% Reduction in Mean Pain Score During Single-blind Treatment Responders	165 participants	—
Number of Subjects With >= 30% Reduction in Mean Pain Score During Single-blind Treatment Non-Responders	90 participants	—

SECONDARY outcome

Timeframe: Week 4

Population: number of subjects that can be analyzed for Change from Baseline at End of Single Blind.

Daily Pain Rating Score:11-point numerical scale 0 ("no pain") to 10 ("worst possible pain"). Responders = ≥30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline.

Outcome measures

Measure	Pregabalin n=165 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Mean Pain Score for Responders at End of Single-blind Treatment Phase. Change From Baseline of Mean of Last 7 Available Pain Scores From Daily Pain Diary While on Single-blind Treatment.	-3.60 score on scale Standard Deviation 1.32	—

SECONDARY outcome

Timeframe: Week 4

Population: number of subjects that can be analyzed for Change from Baseline at End of Single Blind.

Change from baseline of mean of last 7 available pain scores from daily pain diary while on single-blind treatment. Daily Pain Rating Score:11-point numerical scale 0 ("no pain") to 10 ("worst possible pain"). Non-Responders = <30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline.

Outcome measures

Measure	Pregabalin n=90 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Mean Pain Score for Non-responders at End of Single-blind Treatment Phase	-0.49 score on scale Standard Deviation 0.95	—

SECONDARY outcome

Timeframe: Week 9

Population: Number of subjects analyzed for each pain category.

Mean number of days in each pain category. DPRS Daily Pain Rating Score Categories: No pain (score 0), Mild pain (scores 1-3), Moderate pain (scores 4-6), Severe pain (scores 7-10)

Outcome measures

Measure	Pregabalin n=73 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=71 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Categorized Daily Pain Score No pain	3.3 days Standard Deviation 7.6	0.9 days Standard Deviation 3.1
Categorized Daily Pain Score Mild pain	19.5 days Standard Deviation 12.1	17.4 days Standard Deviation 11.9
Categorized Daily Pain Score Moderate pain	7.4 days Standard Deviation 9.5	8.6 days Standard Deviation 8.3
Categorized Daily Pain Score Severe pain	1.2 days Standard Deviation 2.8	1.7 days Standard Deviation 4.5

SECONDARY outcome

Timeframe: Week 9

Number of participants who experienced a meaningful increase in pain also includes participants who took rescue medication for pain due to peripheral neuropathic pain or discontinued from the study .

Outcome measures

Measure	Pregabalin n=80 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=77 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Time to Meaningful Increase in Pain During Double-blind Treatment Phase (Number of Participants)	28 participants	28 participants

SECONDARY outcome

Timeframe: Week 9

Population: FAS population.

Mean Sleep Interference (SI) score at end of Double-Blind treatment = mean of last 7 available SI scores from daily SI diary while on Double-Blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means "pain does not interfere with sleep" and 10 means "pain completely interferes with sleep."

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=75 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Mean Sleep Interference Score	1.81 score on scale Standard Error 0.17	2.52 score on scale Standard Error 0.18

SECONDARY outcome

Timeframe: 0 and 4 weeks

Population: Last observation carried forward (LOCF) approach for patients who do not complete the study will be adopted. This is defined as the mean of the last 7 diary scores while on Double-Blind study drug, up to and including the day after the last day on drug (excluding the taper phase).

Sleep Interference (SI) score at Week 0 and Week 4, end of single-bind treatment. Mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means "pain does not interfere with sleep" and 10 means "pain completely interferes with sleep."

Outcome measures

Measure	Pregabalin n=255 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Weekly Mean Sleep Interference Scores During the Single-Blind Treatment Phase Week 0 - Baseline	4.80 score on scale Standard Deviation 2.44	—
Weekly Mean Sleep Interference Scores During the Single-Blind Treatment Phase Week 4 - end of single-blind treatment	2.72 score on scale Standard Deviation 2.42	—

SECONDARY outcome

Timeframe: Week 9

Mean Sleep Interference scores for weeks 4, 5, 6, 7, 8 and 9. Mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means "pain does not interfere with sleep" and 10 means "pain completely interferes with sleep."

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=75 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase Week 4 (n=73, 70)	1.68 score on scale Standard Deviation 1.57	1.62 score on scale Standard Deviation 1.61
Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase Week 5 (n=70,64)	1.76 score on scale Standard Deviation 1.61	2.24 score on scale Standard Deviation 1.79
Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase Week 6 (n=66,63)	1.85 score on scale Standard Deviation 1.81	2.53 score on scale Standard Deviation 1.69
Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase Week 7 (n=60,56)	1.66 score on scale Standard Deviation 1.63	2.38 score on scale Standard Deviation 1.75
Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase Week 8 (n=63,53)	1.59 score on scale Standard Deviation 1.57	2.36 score on scale Standard Deviation 1.79
Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase Week 9 (n=67,58)	1.66 score on scale Standard Deviation 1.74	2.40 score on scale Standard Deviation 1.86

SECONDARY outcome

Timeframe: 9 weeks

Population: Full Analysis Set (FAS)

Change in Mean SI score: Mean SI score at observation minus mean SI score at week 4. Mean SI Score = mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) is 11-point numerical scale : Zero means "pain does not interfere with sleep" and 10 means "pain completely interferes with sleep."

Outcome measures

Measure	Pregabalin n=73 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=70 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Change in Sleep Interference Scores During Double Blind Treatment Phase Change from randomization to Week 5 (n=70, 64)	0.07 score on scale Standard Error 0.15	0.59 score on scale Standard Error 0.16
Change in Sleep Interference Scores During Double Blind Treatment Phase Change from randomization to Week 6 (n=66, 63)	0.10 score on scale Standard Error 0.16	0.97 score on scale Standard Error 0.16
Change in Sleep Interference Scores During Double Blind Treatment Phase Change from randomization to Week 7 (n=60, 56)	-0.03 score on scale Standard Error 0.16	0.78 score on scale Standard Error 0.17
Change in Sleep Interference Scores During Double Blind Treatment Phase Change from randomization to Week 8 (n=63,53)	-0.13 score on scale Standard Error 0.16	0.72 score on scale Standard Error 0.17
Change in Sleep Interference Scores During Double Blind Treatment Phase Change from randomization to Week 9 (n=67,58)	-0.01 score on scale Standard Error 0.15	0.73 score on scale Standard Error 0.17

SECONDARY outcome

Timeframe: Week 4, Week 9

Change in Scale from randomization to Week 9. Scale to measure Neuropathic Pain -Visual Analog Scale (NeP - VAS): the subject places a mark on the VAS scale (0 to 100) where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=73 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Intensity of Neuropathic Pain -Visual Analog Scale (NeP - VAS)	6.9 scores on a scale Standard Error 2.4	15.9 scores on a scale Standard Error 2.5

SECONDARY outcome

Timeframe: Week 9

Population: FAS population

Mean Change from Randomization in Score from Hospital Anxiety and Depression Scale (HADS): 2 subscales, measuring anxiety (HADS-A)and depression (HADS-D). 7 items in each subscale assessed on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). which yields the score ranging 0-21.

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=75 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Change in Hospital Anxiety and Depression Scale Responses HADS-A	-0.1 score on scale Standard Error 0.3	1.2 score on scale Standard Error 0.3
Change in Hospital Anxiety and Depression Scale Responses HADS-D	-0.4 score on scale Standard Error 0.3	0.8 score on scale Standard Error 0.3

SECONDARY outcome

Timeframe: Week 9

Mean Change: score from observation minus score from randomization: PTSS "Impact" module of 8-items & "Satisfaction" module of 6-items; item scores 1-5.

Mean score for each module transformed onto scale 0- 100, where score 0 =worst possible response and score 100

=best possible response: Score =[(5 - mean non-missing items)*100]/4.

Outcome measures

Measure	Pregabalin n=73 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=70 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Change in Pain Treatment Satisfaction Scale (PTSS) impact of current pain medication	-1.96 score on scale Standard Error 2.53	-7.95 score on scale Standard Error 2.60
Change in Pain Treatment Satisfaction Scale (PTSS) satisfaction with current pain medication	-1.86 score on scale Standard Error 2.04	-8.35 score on scale Standard Error 2.09

SECONDARY outcome

Timeframe: Week 9

Population: FAS Population

Number of subjects that responded to PGIC Categories. PGIC is a subject-rated instrument that measures change in the subject's overall status on a 7-point scale. Scores range from

1 (very much improved) to 7 (very much worse).

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=75 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Patient Global Impression of Change (PGIC) Categories by Number of Subjects Minimally improved	15 participants	17 participants
Patient Global Impression of Change (PGIC) Categories by Number of Subjects No change	6 participants	7 participants
Patient Global Impression of Change (PGIC) Categories by Number of Subjects Minimally worse	0 participants	6 participants
Patient Global Impression of Change (PGIC) Categories by Number of Subjects Very much improved	21 participants	12 participants
Patient Global Impression of Change (PGIC) Categories by Number of Subjects Much improved	35 participants	32 participants
Patient Global Impression of Change (PGIC) Categories by Number of Subjects Much worse	1 participants	0 participants
Patient Global Impression of Change (PGIC) Categories by Number of Subjects Very much worse	0 participants	1 participants

SECONDARY outcome

Timeframe: Week 9

Population: FAS population

Mean Change from Randomization: score at mBPI observation minus score at randomization. mBPI is extent to which pain interferes with daily activities on a 0 (no interference) to 10 (completely interfered) scale.

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=75 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Change in Modified Brief Pain Inventory (mBPI) for Pain Interference or Pain Severity. Pain interference	0.16 score on scale Standard Error 0.19	0.92 score on scale Standard Error 0.20
Change in Modified Brief Pain Inventory (mBPI) for Pain Interference or Pain Severity. Pain severity	0.29 score on scale Standard Error 0.19	1.06 score on scale Standard Error 0.19

SECONDARY outcome

Timeframe: Week 9

two components to the EQ-5D: a Health State Profile (scores from five domains are used to calculate the utility score :0 refers to dead and a score of 1 refers to perfect health) and a Visual Analogue Scale (VAS) (0 represents the worst imaginable health state and 100 represents the best imaginable health state)

Outcome measures

Measure	Pregabalin n=78 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase.	Placebo n=75 Participants subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Change in Euro Quality of Life (EQ-5D) Health State Profile and Visual Analog Scale Components Health State Profile	-0.01 score on scale Standard Error 0.02	-0.07 score on scale Standard Error 0.02
Change in Euro Quality of Life (EQ-5D) Health State Profile and Visual Analog Scale Components Visual Analog Scale	-0.03 score on scale Standard Error 1.83	-2.09 score on scale Standard Error 1.89

Adverse Events

Pregabalin Single-blind Phase

Serious events: 1 serious events

Other events: 196 other events

Deaths: 0 deaths

Pregabalin Double-blind Phase

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Placebo Double-blind Phase

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pregabalin Single-blind Phase subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day) for ≥4 days, then dose adjustment as needed.	Pregabalin Double-blind Phase subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day) for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatent phase.	Placebo Double-blind Phase subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day) for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Infections and infestations Pneumonia	0.39% 1/256 • Number of events 1	0.00% 0/80	0.00% 0/77
Infections and infestations Sepsis	0.39% 1/256 • Number of events 1	0.00% 0/80	0.00% 0/77
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.39% 1/256 • Number of events 1	0.00% 0/80	0.00% 0/77

Other adverse events

Measure	Pregabalin Single-blind Phase subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day) for ≥4 days, then dose adjustment as needed.	Pregabalin Double-blind Phase subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day) for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatent phase.	Placebo Double-blind Phase subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day) for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to placebo received pregabalin 150 mg for 7 days and then placebo for 28 days.
Surgical and medical procedures Asthenia	9.4% 24/256	6.2% 5/80	2.6% 2/77
General disorders Headache	9.4% 24/256	6.2% 5/80	7.8% 6/77
General disorders Pain	2.7% 7/256	3.8% 3/80	6.5% 5/77
Gastrointestinal disorders Constipation	5.1% 13/256	1.2% 1/80	0.00% 0/77
Gastrointestinal disorders Dry mouth	18.0% 46/256	0.00% 0/80	0.00% 0/77
Gastrointestinal disorders Nausea	7.4% 19/256	5.0% 4/80	3.9% 3/77
Metabolism and nutrition disorders Peripheral edema	13.7% 35/256	7.5% 6/80	2.6% 2/77
Musculoskeletal and connective tissue disorders Arthralgia	3.1% 8/256	2.5% 2/80	6.5% 5/77
Metabolism and nutrition disorders Weight gain	6.2% 16/256	6.2% 5/80	1.3% 1/77
Nervous system disorders Balance Disorder	7.0% 18/256	2.5% 2/80	1.3% 1/77
Nervous system disorders Dizziness	35.2% 90/256	8.8% 7/80	10.4% 8/77
Nervous system disorders Euphoria	5.1% 13/256	1.2% 1/80	0.00% 0/77
Nervous system disorders Somnolence	18.8% 48/256	3.8% 3/80	2.6% 2/77
Nervous system disorders Thinking abnormal	11.3% 29/256	1.2% 1/80	0.00% 0/77
Respiratory, thoracic and mediastinal disorders Respiratory tract infection	6.6% 17/256	8.8% 7/80	10.4% 8/77
Eye disorders Abnormal vision	9.0% 23/256	2.5% 2/80	1.3% 1/77
Gastrointestinal disorders Diarrhea	4.7% 12/256	5.0% 4/80	2.6% 2/77

Additional Information

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Results disclosure agreements

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