Trial Outcomes & Findings for Pregabalin Peripheral Neuropathic Pain Study (NCT NCT00141219)

NCT ID: NCT00141219

Last Updated: 2021-02-09

Results Overview

DPRS is 11-point rating scale from 0 (no pain) to 10 (worst possible pain). Subjects instructed to describe their pain (daily upon awakening) during preceding 24 hrs by choosing the appropriate number between 0-10. Mean endpoint pain score was obtained from the last 7 available DPRS scores of the daily pain diary while subject on study medication.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 241 participants
• Primary outcome timeframe: Endpoint- Week 8 or Early Discontinuation
• Results posted on: 2021-02-09

Participant Flow

Study Initiation and Completion Dates: 27 December 2005 to 28 December 2007; 10 study centers in Korea

241 subjects were assigned to study treatment; one subject was randomized but did not receive any study treatment with the reason 'Did not meet entrance criteria'.

Participant milestones

Measure	Pregabalin Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Overall Study STARTED	162	78
Overall Study COMPLETED	138	62
Overall Study NOT COMPLETED	24	16

Reasons for withdrawal

Measure	Pregabalin Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Overall Study Protocol violations	5	4
Overall Study Adverse Event	8	6
Overall Study Lack of Efficacy	5	4
Overall Study Withdrawal by Subject	6	2

Baseline Characteristics

Pregabalin Peripheral Neuropathic Pain Study

Baseline characteristics by cohort

Measure	Pregabalin n=162 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=78 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.	Total n=240 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 10.8 • n=5 Participants	61.3 years STANDARD_DEVIATION 12.9 • n=7 Participants	60.2 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	46 Participants n=7 Participants	129 Participants n=5 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	32 Participants n=7 Participants	111 Participants n=5 Participants

PRIMARY outcome

Timeframe: Endpoint- Week 8 or Early Discontinuation

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. For subjects who did not complete the study, the last 7 available daily pain scores while on study medication were carried forward (LOCF) to calculate the endpoint mean score.

DPRS is 11-point rating scale from 0 (no pain) to 10 (worst possible pain). Subjects instructed to describe their pain (daily upon awakening) during preceding 24 hrs by choosing the appropriate number between 0-10. Mean endpoint pain score was obtained from the last 7 available DPRS scores of the daily pain diary while subject on study medication.

Outcome measures

Measure	Pregabalin n=161 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=77 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Daily Pain Rating Scale (DPRS)- Mean Pain Score (ITT Population)	4.63 score on scale 95% Confidence Interval 0.15 • Interval 4.33 to 4.92	5.13 score on scale 95% Confidence Interval 0.21 • Interval 4.71 to 5.54

SECONDARY outcome

Timeframe: Endpoint- Week 8 or Early Discontinuation

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. For subjects who did not complete the study, the last 7 available daily pain scores while on study medication were carried forward (LOCF) to calculate the endpoint mean score.

DPRS consists of an 11-point rating scale ranging from 0 (no pain) to 10 (worst possible pain). A 30% responder at endpoint is a subject who has a 30% or more reduction in mean pain score at endpoint compared to baseline

Outcome measures

Measure	Pregabalin n=161 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=77 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Daily Pain Rating Scale (DPRS)- Number of 30% Responders (With Respect to Pain Scores) Yes	68 participants	27 participants
Daily Pain Rating Scale (DPRS)- Number of 30% Responders (With Respect to Pain Scores) No	93 participants	50 participants

SECONDARY outcome

Timeframe: Endpoint- Week 8 or Early Discontination

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. For subjects who did not complete the study, the last 7 available daily pain scores while on study medication were carried forward (LOCF) to calculate the endpoint mean score.

DPRS consists of an 11-point rating scale ranging from 0 (no pain) to 10 (worst possible pain). A 50% responder at endpoint is a subject who has a 50% or more reduction in mean pain score at endpoint compared to baseline.

Outcome measures

Measure	Pregabalin n=161 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=77 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Daily Pain Rating Scale (DPRS)- Number of 50% Responders (With Respect to Pain Scores) Yes	42 participants	11 participants
Daily Pain Rating Scale (DPRS)- Number of 50% Responders (With Respect to Pain Scores) No	119 participants	66 participants

SECONDARY outcome

Timeframe: Weeks 1 to 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. Missing Weekly mean scores were not imputed. Number of subjects analyzed differed by week; noted as n= (pregabalin, placebo).

DPRS is 11-point rating scale (0=no pain to 10=worst possible pain). Subjects instructed to describe pain (upon awakening) during preceding 24 hrs by choosing appropriate number between 0-10. Mean endpoint pain score obtained from last 7 available DPRS scores of daily pain diary while subject on study medication. Overall Comparison=8-week average.

Outcome measures

Measure	Pregabalin n=162 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=78 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score Overall Comparison (weeks 1 to 8)	4.91 score on scale Standard Error 0.110	5.29 score on scale Standard Error 0.156
Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score Week 1 (n=161, 77)	5.80 score on scale Standard Error 0.124	6.18 score on scale Standard Error 0.176
Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score Week 2 (n=156, 75)	5.30 score on scale Standard Error 0.125	5.61 score on scale Standard Error 0.177
Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score Week 3 (n=154, 72)	5.02 score on scale Standard Error 0.125	5.42 score on scale Standard Error 0.178
Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score Week 4 (n=151, 68)	4.84 score on scale Standard Error 0.125	5.27 score on scale Standard Error 0.180
Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score Week 5 (n=146, 66)	4.69 score on scale Standard Error 0.126	5.11 score on scale Standard Error 0.181
Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score Week 6 (n=145, 65)	4.64 score on scale Standard Error 0.126	4.93 score on scale Standard Error 0.181
Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score Week 7 (n=142, 62)	4.52 score on scale Standard Error 0.126	4.87 score on scale Standard Error 0.183
Daily Pain Rating Scale (DPRS)- Weekly Mean Pain Score Week 8 (n=138, 62)	4.47 score on scale Standard Error 0.127	4.92 score on scale Standard Error 0.183

SECONDARY outcome

Timeframe: Weeks 1 to 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. Subjects without any post-baseline daily pain scores would have no DAAC; missing DAACs were not imputed.

DAAC is a score used to assess treatment effects averaged over the entire length of the study. DAAC from baseline to weekly mean pain score was derived by calculating the mean of all post-baseline scores minus baseline mean pain score, and then weighing this according to the proportion of the planned study duration the subject actually completed.

Outcome measures

Measure	Pregabalin n=161 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=77 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Duration Adjusted Average Change (DAAC) of (Adjusted) Mean Pain Score	-1.27 score on scale 95% Confidence Interval 0.110 • Interval -1.48 to -1.05	-0.89 score on scale 95% Confidence Interval 0.156 • Interval -1.2 to -0.58

SECONDARY outcome

Timeframe: Endpoint- Week 8 or Early Discontinuation

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. For subjects who did not complete the study, the last 7 available daily sleep interference scores while on study medication were carried forward (LOCF) to calculate the endpoint mean score.

DSIS consists of an 11-point rating scale (0 = pain did not interfere with sleep to 10 = completely interfered with sleep). Higher score indicating greater level of sleep disturbance.

Outcome measures

Measure	Pregabalin n=161 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=77 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Mean Sleep Interference Score Based on Daily Sleep Interference Scale (DSIS).	3.26 score on scale 95% Confidence Interval 0.162 • Interval 2.94 to 3.57	3.91 score on scale 95% Confidence Interval 0.228 • Interval 3.46 to 4.36

SECONDARY outcome

Timeframe: Weeks 1 to 8

Population: ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. Missing Weekly mean scores were not imputed. Number of subjects analyzed differed by week; noted as n = (pregabalin, placebo).

DSIS consists of an 11-point rating scale ranging from 0 = pain did not interfere with sleep to 10 = pain completely interfered with sleep. Overall Comparison= 8-week average.

Outcome measures

Measure	Pregabalin n=162 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=78 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Mean Sleep Score as Computed by DSIS. Week 1 (n= 161, 77)	4.18 score on scale Standard Error 0.145	4.56 score on scale Standard Error 0.205
Mean Sleep Score as Computed by DSIS. Week 2 (n=156, 75)	3.74 score on scale Standard Error 0.145	4.24 score on scale Standard Error 0.206
Mean Sleep Score as Computed by DSIS. Week 3 (n=154, 72)	3.55 score on scale Standard Error 0.146	4.13 score on scale Standard Error 0.207
Mean Sleep Score as Computed by DSIS. Week 4 (n=151, 68)	3.41 score on scale Standard Error 0.146	3.95 score on scale Standard Error 0.208
Mean Sleep Score as Computed by DSIS. Week 5 (n=146, 66)	3.29 score on scale Standard Error 0.146	3.73 score on scale Standard Error 0.209
Mean Sleep Score as Computed by DSIS. Week 6 (n=145, 65)	3.22 score on scale Standard Error 0.147	3.74 score on scale Standard Error 0.210
Mean Sleep Score as Computed by DSIS. Week 7 (n=142, 62)	3.19 score on scale Standard Error 0.147	3.71 score on scale Standard Error 0.211
Mean Sleep Score as Computed by DSIS. Week 8 (n=138, 62)	3.10 score on scale Standard Error 0.147	3.72 score on scale Standard Error 0.211
Mean Sleep Score as Computed by DSIS. Overall Comparison (Weeks 1 to 8)	3.46 score on scale Standard Error 0.134	3.97 score on scale Standard Error 0.189

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. MOS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from analysis.

MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Sleep Disturbance sub-scale scores range from 0 to 100, lower scores indicate less disturbance.

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=74 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Medical Outcome Study (MOS) Sleep Disturbance	28.96 score on scale 95% Confidence Interval 1.550 • Interval 25.9 to 32.01	34.58 score on scale 95% Confidence Interval 2.237 • Interval 30.17 to 38.99

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. MOS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from analysis.

MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Snoring sub-scale scores range from 0 to 100, lower scores indicate less snoring.

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Medical Outcome Study (MOS) Snoring Score	34.21 score on scale 95% Confidence Interval 1.964 • Interval 30.34 to 38.08	29.16 score on scale 95% Confidence Interval 2.788 • Interval 23.66 to 34.65

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. MOS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from the analysis.

MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Awaken Short of Breath or with a Headache sub-scale scores range from 0 to 100, lower scores indicate less difficulty.

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Medical Outcome Study (MOS) Awaken Short of Breath or Headache	6.90 score on scale 95% Confidence Interval 1.116 • Interval 4.7 to 9.09	9.98 score on scale 95% Confidence Interval 1.590 • Interval 6.85 to 13.12

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. MOS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from the analysis.

MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Sleep Quantity sub-scale scores range from 0 to 24 (number of hours slept).

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Medical Outcome Study (MOS) Sleep Quantity	6.46 score on scale 95% Confidence Interval 0.108 • Interval 6.25 to 6.67	6.02 score on scale 95% Confidence Interval 0.154 • Interval 5.72 to 6.33

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. MOS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from the analysis.

MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Optimal Sleep sub-scale score is a binary outcome derived from Sleep Quantity (SQ): the response is YES (or 1) if SQ = 7 or 8 hours per night.

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Medical Outcome Study (MOS) Optimal Sleep: Number of Participants With Optimal Sleep No	85 participants	44 participants
Medical Outcome Study (MOS) Optimal Sleep: Number of Participants With Optimal Sleep Yes	73 participants	31 participants

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. MOS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from the analysis.

MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Sleep Adequacy sub-scale scores range from 0 to 100, higher scores indicate greater sleep adequacy.

Outcome measures

Measure	Pregabalin n=157 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Medical Outcome Study (MOS) Sleep Adequacy	48.81 score on scale 95% Confidence Interval 2.244 • Interval 44.38 to 53.23	46.65 score on scale 95% Confidence Interval 3.194 • Interval 40.36 to 52.95

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. MOS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from the analysis.

MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Somnolence sub-scale scores range from 0 to 100, lower scores indicate less somnolence.

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=74 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Medical Outcome Study (MOS) Somnolence	34.02 score on scale 95% Confidence Interval 1.394 • Interval 31.28 to 36.77	29.31 score on scale 95% Confidence Interval 1.977 • Interval 25.42 to 33.21

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. MOS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from the analysis.

MOS Sleep Scale is a subject-rated questionnaire consisting of 12 items that assess the key constructs of sleep; assesses sleep for the 4 weeks prior to evaluation. The MOS Overall Sleep Problems Index is a 9-item sub-scale; scores range from 0 to 100, lower scores indicate fewer sleep problems.

Outcome measures

Measure	Pregabalin n=157 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=73 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Medical Outcome Study (MOS) Overall Sleep Problems Index	32.27 score on scale 95% Confidence Interval 1.204 • Interval 29.9 to 34.65	34.40 score on scale 95% Confidence Interval 1.730 • Interval 30.99 to 37.81

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. EQ-5D was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from analysis.

EQ-5D, a subject-completed questionnaire, assesses health-related QOL. QOL Health State Profile (HSP) is designed to record subject's level of current health across 5 domains (mobility, self-care, usual activities, pain/discomfort & anxiety/depression); scores are used to calculate EQ-5D Utility Score; range: -0.594 to 1.000 (from worst to best).

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Euro Quality of Life (QOL) (EQ-5D) Utility Score	0.651 score on scale 95% Confidence Interval 0.0192 • Interval 0.614 to 0.689	0.626 score on scale 95% Confidence Interval 0.0274 • Interval 0.572 to 0.68

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. EQ-5D was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from analysis.

EQ-5D is a subject-completed questionnaire to assess health-related QOL (Health State Profile (HSP) & Visual Analog Scale (VAS)). The VAS is designed to rate the subject's current health state on a scale from 0 to 100 where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Euro Quality of Life (EQ-5D) Visual Analog Scale (VAS)	61.53 score on scale 95% Confidence Interval 1.406 • Interval 58.76 to 64.3	58.03 score on scale 95% Confidence Interval 2.008 • Interval 54.07 to 61.99

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. HADS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from analysis.

HADS-A consists of 7 items that are assessed by a score of 0 = no anxiety to 3 = severe feeling of anxiety. The anxiety subscale determines a state of generalized anxiety (including anxious mood, restlessness, anxious thoughts, panic attacks). Score range = 0 to 21; higher scores indicate a greater intensity of anxiety

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Hospital Anxiety and Depression Scale- Anxiety (HADS-A) Score	6.01 score on scale 95% Confidence Interval 0.242 • Interval 5.53 to 6.48	6.86 score on scale 95% Confidence Interval 0.345 • Interval 6.18 to 7.54

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. HADS was measured at baseline and Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from analysis.

HADS-D consists of 7 items that are assessed by a score of 0 = no depression to 3 = severe feeling of depression. The depression subscale focuses on the state of lost interest and diminished pleasure response ("lowering of hedonic tone"). Score range = 0 to 21; higher scores indicate a greater intensity of depression

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Hospital Anxiety and Depression Scale- Depression (HADS-D) Score	7.54 score on scale 95% Confidence Interval 0.259 • Interval 7.03 to 8.05	7.73 score on scale 95% Confidence Interval 0.369 • Interval 7.0 to 8.46

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. PGIC was measured at Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from analysis.

PGIC is a subject-rated instrument that measured change in subject's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improved = minimally improved, much improved, and very much improved; Worse = minimally worse, much worse, and very much worse.

Outcome measures

Measure	Pregabalin n=158 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=75 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Patient Global Impression of Change (PGIC) Improved	118 participants	54 participants
Patient Global Impression of Change (PGIC) No change	29 participants	12 participants
Patient Global Impression of Change (PGIC) Worse	11 participants	9 participants

SECONDARY outcome

Timeframe: Week 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. CGIC was measured at Week 8. For subjects not completing the study, their final data were considered Week 8 data; those without final data were excluded from analysis.

CGIC is a clinician-rated instrument that assesses the subject's overall global improvement on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improved = minimally improved, much improved, and very much improved; Worse = minimally worse, much worse, and very much worse.

Outcome measures

Measure	Pregabalin n=160 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=77 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Clinical Global Impression of Change (CGIC) Improved	117 participants	51 participants
Clinical Global Impression of Change (CGIC) No change	37 participants	16 participants
Clinical Global Impression of Change (CGIC) Worse	6 participants	10 participants

SECONDARY outcome

Timeframe: Weeks 1 to 8

Population: The ITT population consisted of subjects who received ≥1 dose of study medication and had contributed to the analysis of any efficacy parameter. For subjects who did not complete the study, the last 7 observations while on study medication were carried forward (LOCF).

DAAC is a score used to assess treatment effects averaged over the entire length of the study. DAAC from baseline to weekly mean pain score was derived by calculating the mean of all post-baseline scores minus baseline mean pain score, and then weighing this according to the proportion of the planned study duration the subject actually completed.

Outcome measures

Measure	Pregabalin n=161 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=77 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Duration Adjusted Average Change (DAAC) of (Unadjusted) Mean Pain Score	-1.24 score on scale Standard Deviation 1.320	-0.87 score on scale Standard Deviation 1.488

OTHER_PRE_SPECIFIED outcome

Timeframe: Endpoint- Week 8 or Early Discontinuation

Population: Evaluable (EVAL) Population: Subset of ITT subjects with ≥4 daily pain diaries in the 7 days before Visit 2 (randomization) with average score ≥4; ≥14 days of treatment; ≥14 days of DB daily pain diaries; not withdrawn due to "Protocol violation" or "Did not meet entrance criteria"; not previously participated in the study.

DPRS is 11-point rating scale from 0 (no pain) to 10 (worst possible pain). Subjects instructed to describe their pain (daily upon awakening) during preceding 24 hrs by choosing the appropriate number between 0-10. Mean endpoint pain score was obtained from the last 7 available DPRS scores of the daily pain diary while subject on study medication.

Outcome measures

Measure	Pregabalin n=149 Participants Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=68 Participants Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Daily Pain Rating Scale (DPRS)- Mean Pain Scores (Evaluable Population)	4.47 score on scale 95% Confidence Interval 0.156 • Interval 4.16 to 4.78	4.94 score on scale 95% Confidence Interval 0.225 • Interval 4.5 to 5.39

Adverse Events

Pregabalin

Serious events: 2 serious events

Other events: 68 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pregabalin n=162 participants at risk Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=78 participants at risk Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Musculoskeletal and connective tissue disorders Arthritis	0.62% 1/162	0.00% 0/78
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/162	1.3% 1/78
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.62% 1/162	0.00% 0/78

Other adverse events

Measure	Pregabalin n=162 participants at risk Dose levels of pregabalin were 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day which were achieved by taking 75 mg, 150 mg, 225 mg (which was the combination of 75 mg + 150 mg) or 300 mg of pregabalin twice daily (BID), with or without food, once in the morning and once in the evening.	Placebo n=78 participants at risk Subjects who were randomized to placebo remained on placebo throughout the remainder of the study.
Nervous system disorders Dizziness	21.0% 34/162	9.0% 7/78
Nervous system disorders Somnolence	13.6% 22/162	5.1% 4/78
General disorders Face oedema	6.2% 10/162	1.3% 1/78
General disorders Oedema peripheral	6.2% 10/162	0.00% 0/78
Investigations Weight increased	5.6% 9/162	1.3% 1/78
General disorders Generalized oedema	4.3% 7/162	0.00% 0/78
Infections and infestations Nasopharyngitis	3.7% 6/162	1.3% 1/78
Gastrointestinal disorders Constipation	2.5% 4/162	1.3% 1/78
Nervous system disorders Headache	2.5% 4/162	3.8% 3/78
Gastrointestinal disorders Dry mouth	1.9% 3/162	2.6% 2/78
Gastrointestinal disorders Dyspepsia	1.9% 3/162	2.6% 2/78
Cardiac disorders Palpitations	1.2% 2/162	2.6% 2/78
Psychiatric disorders Bulimia nervosa	0.62% 1/162	2.6% 2/78
Psychiatric disorders Insomnia	0.62% 1/162	3.8% 3/78
Gastrointestinal disorders Abdominal pain upper	0.00% 0/162	2.6% 2/78
Psychiatric disorders Sleep disorder	0.00% 0/162	2.6% 2/78
Skin and subcutaneous tissue disorders Rash	0.00% 0/162	2.6% 2/78

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.
• Publication restrictions are in place

Restriction type: OTHER