Trial Outcomes & Findings for Randomized, Double-Blind, Placebo-Controlled Trial Of Pregabalin In Patients With Fibromyalgia. (NCT NCT00333866)

Last Updated: 2021-02-11

Results Overview

Daily pain diary consists of 11-point NRS ranging from 0(no pain) to 10(worst possible pain). Participants rated their pain during past 24 hours, self-assessment done daily at awakening. Baseline=Last 7 available pain scores before taking study medication up to and including Day 1. Final weekly (endpoint) mean pain score is defined as the mean pain score from the last 7 pain diary entries in the study while the participant was on study medication.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

747 participants

Primary outcome timeframe

Baseline, Week 14

Results posted on

2021-02-11

Participant Flow

Recruitment from 73 centers in North America \[Canada (12) and Mexico (4)\], South America \[Venezuela (3)\], Europe \[Denmark (2), France (5), Germany (5), Italy (6), Netherlands (5), Portugal (4), Spain (4), Sweden (4), Switzerland (3) and United Kingdom(5)\] and Asia \[India (4) and Korea (3)\] and Australia (4).

Participant milestones

Participant milestones
Measure	Placebo Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Overall Study STARTED	189	187	184	187
Overall Study TREATED	184	184	182	186
Overall Study COMPLETED	141	123	133	121
Overall Study NOT COMPLETED	48	64	51	66

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Overall Study Adverse Event	23	37	38	47
Overall Study Other	3	2	2	2
Overall Study Lack of Efficacy	8	6	3	5
Overall Study Lost to Follow-up	1	2	2	2
Overall Study Withdrawal by Subject	8	14	4	9
Overall Study Randomized but not Treated	5	3	2	1

Baseline Characteristics

Randomized, Double-Blind, Placebo-Controlled Trial Of Pregabalin In Patients With Fibromyalgia.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=184 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=184 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=182 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=186 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.	Total n=736 Participants Total of all reporting groups
Age, Continuous	48.1 years STANDARD_DEVIATION 11.3 • n=5 Participants	48.4 years STANDARD_DEVIATION 10.8 • n=7 Participants	48.0 years STANDARD_DEVIATION 11.3 • n=5 Participants	49.6 years STANDARD_DEVIATION 11.3 • n=4 Participants	48.5 years STANDARD_DEVIATION 11.2 • n=21 Participants
Sex: Female, Male Female	168 Participants n=5 Participants	167 Participants n=7 Participants	169 Participants n=5 Participants	169 Participants n=4 Participants	673 Participants n=21 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	17 Participants n=7 Participants	13 Participants n=5 Participants	17 Participants n=4 Participants	63 Participants n=21 Participants
Mean Pain Score	6.68 Units on a scale STANDARD_DEVIATION 1.48 • n=5 Participants	6.76 Units on a scale STANDARD_DEVIATION 1.29 • n=7 Participants	6.57 Units on a scale STANDARD_DEVIATION 1.31 • n=5 Participants	6.59 Units on a scale STANDARD_DEVIATION 1.37 • n=4 Participants	6.65 Units on a scale STANDARD_DEVIATION 1.36 • n=21 Participants
Mean Sleep Quality Score	6.01 Units on a scale STANDARD_DEVIATION 1.90 • n=5 Participants	5.94 Units on a scale STANDARD_DEVIATION 1.70 • n=7 Participants	5.94 Units on a scale STANDARD_DEVIATION 1.70 • n=5 Participants	5.91 Units on a scale STANDARD_DEVIATION 1.80 • n=4 Participants	5.95 Units on a scale STANDARD_DEVIATION 1.77 • n=21 Participants
Percentage of Participants With Optimal Sleep Assessed Using MOS-SS	20.33 Percentage of Participants n=5 Participants	25.27 Percentage of Participants n=7 Participants	24.57 Percentage of Participants n=5 Participants	17.03 Percentage of Participants n=4 Participants	87.2 Percentage of Participants n=21 Participants
Medical Outcome Study Sleep Scale (MOS-SS) Sleep Disturbance	60.02 Units on a scale STANDARD_DEVIATION 25.60 • n=5 Participants	61.86 Units on a scale STANDARD_DEVIATION 25.80 • n=7 Participants	59.59 Units on a scale STANDARD_DEVIATION 26.55 • n=5 Participants	60.37 Units on a scale STANDARD_DEVIATION 25.09 • n=4 Participants	60.47 Units on a scale STANDARD_DEVIATION 25.72 • n=21 Participants
Medical Outcome Study Sleep Scale (MOS-SS) Snoring	31.05 Units on a scale STANDARD_DEVIATION 32.39 • n=5 Participants	32.53 Units on a scale STANDARD_DEVIATION 30.82 • n=7 Participants	29.77 Units on a scale STANDARD_DEVIATION 32.52 • n=5 Participants	32.09 Units on a scale STANDARD_DEVIATION 32.20 • n=4 Participants	31.36 Units on a scale STANDARD_DEVIATION 31.94 • n=21 Participants
Medical Outcome Study Sleep Scale (MOS-SS) Shortness of Breath, Headache	34.18 Units on a scale STANDARD_DEVIATION 32.96 • n=5 Participants	36.70 Units on a scale STANDARD_DEVIATION 31.01 • n=7 Participants	38.31 Units on a scale STANDARD_DEVIATION 32.46 • n=5 Participants	37.07 Units on a scale STANDARD_DEVIATION 31.54 • n=4 Participants	36.55 Units on a scale STANDARD_DEVIATION 31.97 • n=21 Participants
Medical Outcome Study Sleep Scale (MOS-SS) Quantity of Sleep	5.47 Units on a scale STANDARD_DEVIATION 1.54 • n=5 Participants	5.59 Units on a scale STANDARD_DEVIATION 1.66 • n=7 Participants	5.61 Units on a scale STANDARD_DEVIATION 1.68 • n=5 Participants	5.45 Units on a scale STANDARD_DEVIATION 1.65 • n=4 Participants	5.53 Units on a scale STANDARD_DEVIATION 1.63 • n=21 Participants
Medical Outcome Study Sleep Scale (MOS-SS) Sleep Adequacy	24.70 Units on a scale STANDARD_DEVIATION 23.39 • n=5 Participants	24.43 Units on a scale STANDARD_DEVIATION 24.80 • n=7 Participants	24.30 Units on a scale STANDARD_DEVIATION 22.83 • n=5 Participants	25.03 Units on a scale STANDARD_DEVIATION 24.25 • n=4 Participants	24.62 Units on a scale STANDARD_DEVIATION 23.79 • n=21 Participants
Medical Outcome Study Sleep Scale (MOS-SS) Somnolence	41.68 Units on a scale STANDARD_DEVIATION 21.78 • n=5 Participants	44.03 Units on a scale STANDARD_DEVIATION 22.80 • n=7 Participants	42.37 Units on a scale STANDARD_DEVIATION 23.91 • n=5 Participants	42.97 Units on a scale STANDARD_DEVIATION 23.92 • n=4 Participants	42.77 Units on a scale STANDARD_DEVIATION 23.09 • n=21 Participants
Medical Outcome Study Sleep Scale (MOS-SS) Overall Sleep Problem Index	57.46 Units on a scale STANDARD_DEVIATION 17.27 • n=5 Participants	59.27 Units on a scale STANDARD_DEVIATION 19.24 • n=7 Participants	58.11 Units on a scale STANDARD_DEVIATION 18.94 • n=5 Participants	58.05 Units on a scale STANDARD_DEVIATION 18.12 • n=4 Participants	58.22 Units on a scale STANDARD_DEVIATION 18.38 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Physical Impairment	4.04 Units on a scale STANDARD_DEVIATION 2.18 • n=5 Participants	3.88 Units on a scale STANDARD_DEVIATION 2.13 • n=7 Participants	3.87 Units on a scale STANDARD_DEVIATION 2.12 • n=5 Participants	3.75 Units on a scale STANDARD_DEVIATION 2.15 • n=4 Participants	3.88 Units on a scale STANDARD_DEVIATION 2.14 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Feel Good	7.50 Units on a scale STANDARD_DEVIATION 2.61 • n=5 Participants	7.46 Units on a scale STANDARD_DEVIATION 2.77 • n=7 Participants	7.63 Units on a scale STANDARD_DEVIATION 2.53 • n=5 Participants	7.77 Units on a scale STANDARD_DEVIATION 2.65 • n=4 Participants	7.59 Units on a scale STANDARD_DEVIATION 2.64 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Work Missed	3.38 Units on a scale STANDARD_DEVIATION 3.34 • n=5 Participants	3.35 Units on a scale STANDARD_DEVIATION 3.18 • n=7 Participants	3.22 Units on a scale STANDARD_DEVIATION 3.36 • n=5 Participants	2.86 Units on a scale STANDARD_DEVIATION 2.99 • n=4 Participants	3.20 Units on a scale STANDARD_DEVIATION 3.22 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Do Work	6.96 Units on a scale STANDARD_DEVIATION 2.24 • n=5 Participants	6.54 Units on a scale STANDARD_DEVIATION 2.23 • n=7 Participants	6.68 Units on a scale STANDARD_DEVIATION 1.96 • n=5 Participants	6.62 Units on a scale STANDARD_DEVIATION 2.01 • n=4 Participants	6.70 Units on a scale STANDARD_DEVIATION 2.12 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Pain	7.35 Units on a scale STANDARD_DEVIATION 1.63 • n=5 Participants	7.24 Units on a scale STANDARD_DEVIATION 1.48 • n=7 Participants	7.09 Units on a scale STANDARD_DEVIATION 1.62 • n=5 Participants	7.15 Units on a scale STANDARD_DEVIATION 1.60 • n=4 Participants	7.21 Units on a scale STANDARD_DEVIATION 1.58 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Fatigue	7.85 Units on a scale STANDARD_DEVIATION 1.84 • n=5 Participants	7.45 Units on a scale STANDARD_DEVIATION 2.14 • n=7 Participants	7.34 Units on a scale STANDARD_DEVIATION 2.02 • n=5 Participants	7.56 Units on a scale STANDARD_DEVIATION 2.04 • n=4 Participants	7.55 Units on a scale STANDARD_DEVIATION 2.02 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Rested	7.71 Units on a scale STANDARD_DEVIATION 2.03 • n=5 Participants	7.61 Units on a scale STANDARD_DEVIATION 2.08 • n=7 Participants	7.55 Units on a scale STANDARD_DEVIATION 1.96 • n=5 Participants	7.44 Units on a scale STANDARD_DEVIATION 2.02 • n=4 Participants	7.58 Units on a scale STANDARD_DEVIATION 2.02 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Stiffness	7.52 Units on a scale STANDARD_DEVIATION 2.13 • n=5 Participants	7.19 Units on a scale STANDARD_DEVIATION 2.07 • n=7 Participants	7.03 Units on a scale STANDARD_DEVIATION 2.02 • n=5 Participants	7.28 Units on a scale STANDARD_DEVIATION 2.24 • n=4 Participants	7.26 Units on a scale STANDARD_DEVIATION 2.12 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Anxiety	5.38 Units on a scale STANDARD_DEVIATION 3.09 • n=5 Participants	5.27 Units on a scale STANDARD_DEVIATION 2.96 • n=7 Participants	5.35 Units on a scale STANDARD_DEVIATION 2.86 • n=5 Participants	5.35 Units on a scale STANDARD_DEVIATION 2.97 • n=4 Participants	5.34 Units on a scale STANDARD_DEVIATION 2.97 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores FIQ Depression	4.85 Units on a scale STANDARD_DEVIATION 3.12 • n=5 Participants	4.73 Units on a scale STANDARD_DEVIATION 2.93 • n=7 Participants	4.79 Units on a scale STANDARD_DEVIATION 3.01 • n=5 Participants	4.65 Units on a scale STANDARD_DEVIATION 3.00 • n=4 Participants	4.76 Units on a scale STANDARD_DEVIATION 3.01 • n=21 Participants
Fibromyalgia Impact Questionnaire (FIQ) Total Scores	62.58 Units on a scale STANDARD_DEVIATION 14.85 • n=5 Participants	60.75 Units on a scale STANDARD_DEVIATION 14.77 • n=7 Participants	60.59 Units on a scale STANDARD_DEVIATION 14.59 • n=5 Participants	60.40 Units on a scale STANDARD_DEVIATION 13.87 • n=4 Participants	61.08 Units on a scale STANDARD_DEVIATION 14.52 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) Physical Functioning	42.93 Units on a scale STANDARD_DEVIATION 21.04 • n=5 Participants	44.71 Units on a scale STANDARD_DEVIATION 20.29 • n=7 Participants	42.52 Units on a scale STANDARD_DEVIATION 22.17 • n=5 Participants	43.54 Units on a scale STANDARD_DEVIATION 20.39 • n=4 Participants	43.43 Units on a scale STANDARD_DEVIATION 20.94 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) Physical Role Limitations	37.14 Units on a scale STANDARD_DEVIATION 22.75 • n=5 Participants	40.79 Units on a scale STANDARD_DEVIATION 25.58 • n=7 Participants	41.44 Units on a scale STANDARD_DEVIATION 25.39 • n=5 Participants	39.46 Units on a scale STANDARD_DEVIATION 24.71 • n=4 Participants	39.69 Units on a scale STANDARD_DEVIATION 24.63 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) Emotional Role Limitations	59.61 Units on a scale STANDARD_DEVIATION 29.52 • n=5 Participants	60.61 Units on a scale STANDARD_DEVIATION 29.23 • n=7 Participants	61.54 Units on a scale STANDARD_DEVIATION 28.94 • n=5 Participants	61.31 Units on a scale STANDARD_DEVIATION 29.50 • n=4 Participants	60.76 Units on a scale STANDARD_DEVIATION 29.25 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) Social Functioning	54.44 Units on a scale STANDARD_DEVIATION 26.95 • n=5 Participants	56.79 Units on a scale STANDARD_DEVIATION 26.00 • n=7 Participants	53.93 Units on a scale STANDARD_DEVIATION 26.55 • n=5 Participants	53.70 Units on a scale STANDARD_DEVIATION 25.55 • n=4 Participants	54.72 Units on a scale STANDARD_DEVIATION 26.24 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) Mental Health	56.48 Units on a scale STANDARD_DEVIATION 20.68 • n=5 Participants	56.41 Units on a scale STANDARD_DEVIATION 20.49 • n=7 Participants	57.56 Units on a scale STANDARD_DEVIATION 21.70 • n=5 Participants	56.71 Units on a scale STANDARD_DEVIATION 20.39 • n=4 Participants	56.78 Units on a scale STANDARD_DEVIATION 20.77 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) Bodily Pain	29.28 Units on a scale STANDARD_DEVIATION 15.61 • n=5 Participants	28.67 Units on a scale STANDARD_DEVIATION 13.65 • n=7 Participants	28.30 Units on a scale STANDARD_DEVIATION 13.62 • n=5 Participants	28.70 Units on a scale STANDARD_DEVIATION 13.20 • n=4 Participants	28.74 Units on a scale STANDARD_DEVIATION 14.03 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) Vitality	26.46 Units on a scale STANDARD_DEVIATION 16.76 • n=5 Participants	27.88 Units on a scale STANDARD_DEVIATION 17.67 • n=7 Participants	28.78 Units on a scale STANDARD_DEVIATION 19.94 • n=5 Participants	27.42 Units on a scale STANDARD_DEVIATION 19.14 • n=4 Participants	27.63 Units on a scale STANDARD_DEVIATION 18.39 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) General Health Perception	41.65 Units on a scale STANDARD_DEVIATION 18.35 • n=5 Participants	42.12 Units on a scale STANDARD_DEVIATION 19.24 • n=7 Participants	45.56 Units on a scale STANDARD_DEVIATION 18.56 • n=5 Participants	44.58 Units on a scale STANDARD_DEVIATION 18.23 • n=4 Participants	43.47 Units on a scale STANDARD_DEVIATION 18.63 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) Mental Component Score	40.11 Units on a scale STANDARD_DEVIATION 11.57 • n=5 Participants	40.45 Units on a scale STANDARD_DEVIATION 11.72 • n=7 Participants	40.79 Units on a scale STANDARD_DEVIATION 13.15 • n=5 Participants	40.37 Units on a scale STANDARD_DEVIATION 12.14 • n=4 Participants	40.43 Units on a scale STANDARD_DEVIATION 12.13 • n=21 Participants
36-Item Short-Form Health Survey (SF-36) Physical Component Score	31.87 Units on a scale STANDARD_DEVIATION 7.59 • n=5 Participants	32.60 Units on a scale STANDARD_DEVIATION 7.43 • n=7 Participants	32.51 Units on a scale STANDARD_DEVIATION 8.16 • n=5 Participants	32.42 Units on a scale STANDARD_DEVIATION 7.03 • n=4 Participants	32.35 Units on a scale STANDARD_DEVIATION 7.55 • n=21 Participants
Multidimensional Assessment of Fatigue (MAF)	34.89 Units on a scale STANDARD_DEVIATION 7.52 • n=5 Participants	34.97 Units on a scale STANDARD_DEVIATION 7.71 • n=7 Participants	33.98 Units on a scale STANDARD_DEVIATION 8.29 • n=5 Participants	34.87 Units on a scale STANDARD_DEVIATION 7.70 • n=4 Participants	34.68 Units on a scale STANDARD_DEVIATION 7.80 • n=21 Participants
Hospital Anxiety and Depression Scale (HADS) HADS Anxiety (HADS-A) Total	8.95 Units on a scale STANDARD_DEVIATION 4.52 • n=5 Participants	8.96 Units on a scale STANDARD_DEVIATION 4.50 • n=7 Participants	8.75 Units on a scale STANDARD_DEVIATION 4.44 • n=5 Participants	8.85 Units on a scale STANDARD_DEVIATION 4.58 • n=4 Participants	8.88 Units on a scale STANDARD_DEVIATION 4.51 • n=21 Participants
Hospital Anxiety and Depression Scale (HADS) HADS Depression (HADS-D) Total	7.83 Units on a scale STANDARD_DEVIATION 4.17 • n=5 Participants	7.16 Units on a scale STANDARD_DEVIATION 4.03 • n=7 Participants	7.66 Units on a scale STANDARD_DEVIATION 4.32 • n=5 Participants	7.39 Units on a scale STANDARD_DEVIATION 4.28 • n=4 Participants	7.51 Units on a scale STANDARD_DEVIATION 4.20 • n=21 Participants
Pain Visual Analogue Scale (VAS) Scores	72.72 millimeter (mm) STANDARD_DEVIATION 14.09 • n=5 Participants	72.43 millimeter (mm) STANDARD_DEVIATION 13.61 • n=7 Participants	70.92 millimeter (mm) STANDARD_DEVIATION 13.69 • n=5 Participants	71.43 millimeter (mm) STANDARD_DEVIATION 13.51 • n=4 Participants	71.88 millimeter (mm) STANDARD_DEVIATION 13.72 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 14

Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study medication, regardless of medication compliance. Missing data were imputed using last observation carried forward (LOCF) method. 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Outcome measures

Outcome measures
Measure	Placebo n=184 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=184 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=181 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=186 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Mean Pain Score at Endpoint (Up to Week 14)	-0.73 Units on a scale Standard Error 0.14	-1.06 Units on a scale Standard Error 0.14	-1.29 Units on a scale Standard Error 0.14	-0.96 Units on a scale Standard Error 0.14

PRIMARY outcome

Timeframe: Week 14

Population: FAS included all randomized participants who received at least 1 dose of study medication, regardless of medication compliance. Missing data were imputed using LOCF method. 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Number of participants with categorical change in overall status. PGIC: a participant-rated instrument assessing change in participant's overall status from baseline, on a scale ranging from 1 (very much improved) to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Placebo n=169 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=164 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=165 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=155 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Patient Global Impression of Change (PGIC) Very much worse	3 participants	5 participants	2 participants	3 participants
Patient Global Impression of Change (PGIC) Very much improved	7 participants	13 participants	16 participants	20 participants
Patient Global Impression of Change (PGIC) Much improved	43 participants	45 participants	50 participants	46 participants
Patient Global Impression of Change (PGIC) Minimally improved	45 participants	50 participants	55 participants	41 participants
Patient Global Impression of Change (PGIC) No change	43 participants	28 participants	27 participants	25 participants
Patient Global Impression of Change (PGIC) Minimally worse	11 participants	9 participants	7 participants	10 participants
Patient Global Impression of Change (PGIC) Much worse	17 participants	14 participants	8 participants	10 participants

SECONDARY outcome

Timeframe: Baseline, Week 14

Daily quality of sleep diary consists of 11-point NRS ranging from 0(best possible sleep) to 10(worst possible sleep). Participants rated their quality of sleep during past 24 hours, self-assessment done daily upon awakening. Baseline=Last 7 available scores before taking study medication up to and including Day 1. The endpoint (up to week 14) mean quality of sleep score was based on Least Squares (LS) Means using ANCOVA, with treatment group and center in the model and the baseline mean sleep score used as the covariate. Final weekly (endpoint) mean sleep quality score is defined as the mean sleep quality score from the last 7 sleep diary entries in the study while the participant was on study medication.

Outcome measures

Outcome measures
Measure	Placebo n=184 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=184 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=181 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=186 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Mean Sleep Quality Score at Endpoint (Up to Week 14)	-0.94 Units on a scale Standard Error 0.15	-1.42 Units on a scale Standard Error 0.15	-1.72 Units on a scale Standard Error 0.15	-1.95 Units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14

Population: FAS included all randomized participants who received at least 1 dose of study medication, regardless of medication compliance. 'N' (number of participants analyzed) signifies participants evaluable for this measure. 'n' participants evaluable at given time point for each group, respectively.

Daily quality of sleep diary consists of 11-point NRS ranging from 0(best possible sleep) to 10(worst possible sleep). Participants rated their quality of sleep during past 24 hours, self-assessment done daily upon awakening. Baseline=Last 7 available scores before taking study medication up to and including Day 1. The weekly mean quality of sleep score was based on LS Means using mixed model repeated measures ANCOVA, with treatment, center, week, and treatment-by-week interaction in the model and the baseline mean sleep score used as the covariate. Weekly mean sleep quality score is defined as the mean of the last 7 daily sleep diary entries.

Outcome measures

Outcome measures
Measure	Placebo n=183 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=179 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=174 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=178 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Weekly Mean Sleep Quality Score Overall (n=183,179,174,178)	-0.91 Units on a scale Standard Error 0.12	-1.57 Units on a scale Standard Error 0.12	-1.76 Units on a scale Standard Error 0.12	-2.07 Units on a scale Standard Error 0.12
Change From Baseline in Weekly Mean Sleep Quality Score Week 1 (n=183,179,174,178)	-0.38 Units on a scale Standard Error 0.14	-1.20 Units on a scale Standard Error 0.15	-1.08 Units on a scale Standard Error 0.15	-1.23 Units on a scale Standard Error 0.15
Change From Baseline in Weekly Mean Sleep Quality Score Week 2 (n=180,172,168,174)	-0.62 Units on a scale Standard Error 0.14	-1.48 Units on a scale Standard Error 0.15	-1.43 Units on a scale Standard Error 0.15	-1.59 Units on a scale Standard Error 0.15
Change From Baseline in Weekly Mean Sleep Quality Score Week 3 (n=174, 164, 159,163)	-0.75 Units on a scale Standard Error 0.15	-1.42 Units on a scale Standard Error 0.15	-1.56 Units on a scale Standard Error 0.15	-1.90 Units on a scale Standard Error 0.15
Change From Baseline in Weekly Mean Sleep Quality Score Week 4 (n=165,157,155,156)	-0.73 Units on a scale Standard Error 0.15	-1.52 Units on a scale Standard Error 0.15	-1.67 Units on a scale Standard Error 0.15	-2.01 Units on a scale Standard Error 0.15
Change From Baseline in Weekly Mean Sleep Quality Score Week 5 (n=163, 150, 152,148)	-0.82 Units on a scale Standard Error 0.15	-1.67 Units on a scale Standard Error 0.15	-1.69 Units on a scale Standard Error 0.15	-1.99 Units on a scale Standard Error 0.15
Change From Baseline in Weekly Mean Sleep Quality Score Week 6 (n=159,145,148,144)	-0.84 Units on a scale Standard Error 0.15	-1.56 Units on a scale Standard Error 0.15	-1.76 Units on a scale Standard Error 0.16	-2.15 Units on a scale Standard Error 0.16
Change From Baseline in Weekly Mean Sleep Quality Score Week 7 (n=155,140,144,133)	-0.91 Units on a scale Standard Error 0.15	-1.50 Units on a scale Standard Error 0.16	-1.83 Units on a scale Standard Error 0.16	-2.20 Units on a scale Standard Error 0.16
Change From Baseline in Weekly Mean Sleep Quality Score Week 8 (n=149,133,142,127)	-0.99 Units on a scale Standard Error 0.15	-1.60 Units on a scale Standard Error 0.16	-1.95 Units on a scale Standard Error 0.16	-2.25 Units on a scale Standard Error 0.16
Change From Baseline in Weekly Mean Sleep Quality Score Week 9 (n=146,128,141,126)	-1.11 Units on a scale Standard Error 0.15	-1.64 Units on a scale Standard Error 0.16	-1.94 Units on a scale Standard Error 0.16	-2.24 Units on a scale Standard Error 0.16
Change From Baseline in Weekly Mean Sleep Quality Score Week 10 (n=144,125,139,126)	-1.14 Units on a scale Standard Error 0.16	-1.75 Units on a scale Standard Error 0.16	-2.03 Units on a scale Standard Error 0.16	-2.34 Units on a scale Standard Error 0.17
Change From Baseline in Weekly Mean Sleep Quality Score Week 11 (n=143,123,137,121)	-1.09 Units on a scale Standard Error 0.16	-1.65 Units on a scale Standard Error 0.17	-1.92 Units on a scale Standard Error 0.16	-2.24 Units on a scale Standard Error 0.17
Change From Baseline in Weekly Mean Sleep Quality Score Week 12 (n=141,121,135,119)	-1.22 Units on a scale Standard Error 0.16	-1.62 Units on a scale Standard Error 0.17	-1.95 Units on a scale Standard Error 0.16	-2.29 Units on a scale Standard Error 0.17
Change From Baseline in Weekly Mean Sleep Quality Score Week 13 (n=140,120,133,118)	-1.05 Units on a scale Standard Error 0.16	-1.66 Units on a scale Standard Error 0.17	-1.93 Units on a scale Standard Error 0.17	-2.26 Units on a scale Standard Error 0.17
Change From Baseline in Weekly Mean Sleep Quality Score Week 14 (n=134,115,128,111)	-1.08 Units on a scale Standard Error 0.16	-1.73 Units on a scale Standard Error 0.17	-1.95 Units on a scale Standard Error 0.17	-2.29 Units on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: FAS included all randomized participants who received at least 1 dose of study medication, regardless of medication compliance. Missing data were handled using LOCF method. 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Participant-rated 12 item questionnaire assess constructs of sleep over past week.7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence (range:0-100); sleep quantity(range:0-24), optimal sleep(yes or no), as well as a 9-item overall sleep problems index. Except Adequacy, Optimal, Quantity of sleep, higher scores=more impairment. Scores transformed(actual raw score minus lowest possible score divided by possible raw score range\*100);total score range:0-100,higher score=more disturbance.

Outcome measures

Outcome measures
Measure	Placebo n=182 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=182 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=175 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=182 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Percentage of Participants With Optimal Sleep Assessed Using MOS-SS	30.8 Percentage of participants	33.5 Percentage of participants	44.0 Percentage of participants	32.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: FAS included all randomized participants who received at least 1 dose of study medication, regardless of medication compliance. Missing data were handled using LOCF method. 'N' (number of participants analyzed)=participants evaluable for this measure. 'n'=participants evaluable for specified category for each arm group.

Outcome measures

Outcome measures
Measure	Placebo n=183 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=183 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=179 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=185 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Medical Outcomes Study (MOS): Sub-scales at Week 14 Somnolence (n=182,182,177,184)	-0.10 Units on a scale Standard Error 1.50	0.67 Units on a scale Standard Error 1.49	0.61 Units on a scale Standard Error 1.53	1.92 Units on a scale Standard Error 1.49
Change From Baseline in Medical Outcomes Study (MOS): Sub-scales at Week 14 Sleep Disturbance (n=183,183,177,185)	-5.99 Units on a scale Standard Error 1.79	-13.18 Units on a scale Standard Error 1.78	-19.26 Units on a scale Standard Error 1.84	-18.70 Units on a scale Standard Error 1.78
Change From Baseline in Medical Outcomes Study (MOS): Sub-scales at Week 14 Snoring (n=172,174,174,177)	-0.03 Units on a scale Standard Error 1.75	1.17 Units on a scale Standard Error 1.73	4.89 Units on a scale Standard Error 1.75	5.87 Units on a scale Standard Error 1.73
Change From Baseline in Medical Outcomes Study (MOS): Sub-scales at Week 14 Shortness of Breath, Headache (n=182,182,177,184)	-0.67 Units on a scale Standard Error 1.92	-9.62 Units on a scale Standard Error 1.91	-12.59 Units on a scale Standard Error 1.96	-9.91 Units on a scale Standard Error 1.91
Change From Baseline in Medical Outcomes Study (MOS): Sub-scales at Week 14 Quantity of Sleep (n=182,182,175,182)	0.41 Units on a scale Standard Error 0.10	0.61 Units on a scale Standard Error 0.10	0.91 Units on a scale Standard Error 0.11	0.76 Units on a scale Standard Error 0.10
Change From Baseline in Medical Outcomes Study (MOS): Sub-scales at Week 14 Sleep Adequacy (n=183,183,179,185)	7.62 Units on a scale Standard Error 1.93	10.19 Units on a scale Standard Error 1.92	16.76 Units on a scale Standard Error 1.96	11.97 Units on a scale Standard Error 1.92
Change From Baseline in Medical Outcomes Study (MOS): Sub-scales at Week 14 Overall Sleep Problem Index (n=181,181,174,184)	-4.83 Units on a scale Standard Error 1.35	-9.19 Units on a scale Standard Error 1.34	-13.07 Units on a scale Standard Error 1.39	-11.72 Units on a scale Standard Error 1.34

SECONDARY outcome

Timeframe: Baseline, Week 14

FIQ: 20-item self-administered questionnaire designed to assess areas such as health status, progress, and outcomes in participants with fibromyalgia. 11 items related to physical functioning, other items assess pain, fatigue, stiffness, difficulty working, and symptoms of anxiousness and depression. FIQ contains 10 sub-scales scored from 0 to 10, with higher scores indicating more impairment in the subscale attribute. Total score range from 0 to 100 with higher scores indicating more impairment.

Outcome measures

Outcome measures
Measure	Placebo n=183 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=184 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=179 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=186 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Physical Impairment (n=183,184,179,186)	-0.09 Units on a scale Standard Error 0.14	-0.26 Units on a scale Standard Error 0.14	-0.35 Units on a scale Standard Error 0.14	-0.26 Units on a scale Standard Error 0.14
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Feel Good (n=182,184,178,183)	-1.15 Units on a scale Standard Error 0.22	-1.11 Units on a scale Standard Error 0.22	-1.77 Units on a scale Standard Error 0.22	-1.26 Units on a scale Standard Error 0.22
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Work Missed (n=182,181,178,184)	-0.13 Units on a scale Standard Error 0.19	-0.29 Units on a scale Standard Error 0.18	-0.75 Units on a scale Standard Error 0.19	-0.27 Units on a scale Standard Error 0.18
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Do Work (n=182,183,179,185)	-0.90 Units on a scale Standard Error 0.18	-1.04 Units on a scale Standard Error 0.18	-1.60 Units on a scale Standard Error 0.18	-0.98 Units on a scale Standard Error 0.18
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Pain (n=183,184,179,185)	-0.97 Units on a scale Standard Error 0.17	-1.18 Units on a scale Standard Error 0.17	-1.72 Units on a scale Standard Error 0.17	-1.10 Units on a scale Standard Error 0.17
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Fatigue (n=183,184,179,184)	-0.81 Units on a scale Standard Error 0.18	-0.86 Units on a scale Standard Error 0.18	-1.36 Units on a scale Standard Error 0.18	-1.05 Units on a scale Standard Error 0.18
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Rested (n=183,184,179,185)	-0.94 Units on a scale Standard Error 0.19	-1.17 Units on a scale Standard Error 0.19	-1.47 Units on a scale Standard Error 0.20	-1.40 Units on a scale Standard Error 0.19
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Stiffness (n=183,184,179,185)	-1.06 Units on a scale Standard Error 0.18	-1.02 Units on a scale Standard Error 0.18	-1.28 Units on a scale Standard Error 0.18	-0.94 Units on a scale Standard Error 0.18
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Anxiety (n=183,184,179,185)	-0.48 Units on a scale Standard Error 0.20	-0.66 Units on a scale Standard Error 0.20	-1.12 Units on a scale Standard Error 0.20	-0.68 Units on a scale Standard Error 0.20
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Subscale Scores at Week 14 FIQ Depression (n=181,184,179,184)	-0.22 Units on a scale Standard Error 0.20	-0.56 Units on a scale Standard Error 0.20	-1.19 Units on a scale Standard Error 0.20	-0.43 Units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Week 14

Outcome measures

Outcome measures
Measure	Placebo n=184 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=184 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=179 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=186 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Fibromyalgia Impact Questionnaire (FIQ) Total Scores at Week 14	-6.94 Units on a scale Standard Error 1.30	-8.11 Units on a scale Standard Error 1.29	-12.79 Units on a scale Standard Error 1.32	-8.38 Units on a scale Standard Error 1.29

SECONDARY outcome

Timeframe: Baseline, Week 14

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning) and is reported as 2 summary scores; Physical Component Score and Mental Component Score. Total score range for the summary scores = 0- 100, where higher score represents higher level of functioning.

Outcome measures

Outcome measures
Measure	Placebo n=184 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=184 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=178 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=186 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 Emotional Role Limitations (n=183,183,177,185)	-2.31 Units on a scale Standard Error 1.94	1.44 Units on a scale Standard Error 1.93	3.93 Units on a scale Standard Error 1.98	1.56 Units on a scale Standard Error 1.93
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 Bodily Pain (n=183,184,178,186)	4.95 Units on a scale Standard Error 1.31	7.77 Units on a scale Standard Error 1.30	10.32 Units on a scale Standard Error 1.33	7.53 Units on a scale Standard Error 1.30
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 Vitality (n=183,184,178,186)	4.15 Units on a scale Standard Error 1.42	4.89 Units on a scale Standard Error 1.41	9.25 Units on a scale Standard Error 1.45	7.29 Units on a scale Standard Error 1.41
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 General Health Perception (n=183,184,177,186)	0.94 Units on a scale Standard Error 1.16	2.76 Units on a scale Standard Error 1.15	3.67 Units on a scale Standard Error 1.18	2.21 Units on a scale Standard Error 1.14
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 Mental Component Score (n=182,183,176,184)	-1.27 Units on a scale Standard Error 0.81	0.87 Units on a scale Standard Error 0.81	2.39 Units on a scale Standard Error 0.83	1.35 Units on a scale Standard Error 0.81
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 Physical Component Score (n=182,183,176,184)	2.47 Units on a scale Standard Error 0.52	2.60 Units on a scale Standard Error 0.52	3.01 Units on a scale Standard Error 0.53	2.34 Units on a scale Standard Error 0.52
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 Physical Functioning (n=184,184,177,186)	4.64 Units on a scale Standard Error 1.32	5.22 Units on a scale Standard Error 1.31	6.63 Units on a scale Standard Error 1.35	4.13 Units on a scale Standard Error 1.31
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 Physical Role Limitations (n=183,183,177,185)	4.01 Units on a scale Standard Error 1.63	4.40 Units on a scale Standard Error 1.62	5.50 Units on a scale Standard Error 1.66	5.03 Units on a scale Standard Error 1.62
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 Social Functioning (n=183,184,178,186)	0.75 Units on a scale Standard Error 1.77	4.10 Units on a scale Standard Error 1.76	5.76 Units on a scale Standard Error 1.81	3.60 Units on a scale Standard Error 1.76
Change From Baseline in Short Form-36 (SF-36) Health Survey at Week 14 Mental Health (n=183,184,178,186)	-1.67 Units on a scale Standard Error 1.35	1.65 Units on a scale Standard Error 1.34	4.25 Units on a scale Standard Error 1.38	2.41 Units on a scale Standard Error 1.34

SECONDARY outcome

Timeframe: Baseline, Week 14

MAF is a 16-item self-administered questionnaire that yields a Global Fatigue Index (GFI), measures 4 dimensions of fatigue: degree and severity, amount of distress it causes, its timing and degree to which fatigue interferes with activities of daily living. Only 15 items are used to calculate the GFI. GFI score range from 1 (no fatigue) to 50 (severe fatigue).

Outcome measures

Outcome measures
Measure	Placebo n=183 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=176 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=175 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=181 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Multidimensional Assessment of Fatigue (MAF) at Week 14	-1.91 Units on a scale Standard Error 0.62	-2.78 Units on a scale Standard Error 0.63	-3.32 Units on a scale Standard Error 0.64	-2.19 Units on a scale Standard Error 0.62

SECONDARY outcome

Timeframe: Baseline, Week 14

HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=182 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=181 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=176 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=185 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 14 HADS Anxiety (HADS-A) Total	-0.31 Units on a scale Standard Error 0.25	-0.42 Units on a scale Standard Error 0.25	-0.81 Units on a scale Standard Error 0.26	-0.90 Units on a scale Standard Error 0.25
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 14 HADS Depression (HADS-D) Total	-0.11 Units on a scale Standard Error 0.24	-0.33 Units on a scale Standard Error 0.24	-0.70 Units on a scale Standard Error 0.25	0.04 Units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline, Week 14

Pain visual analog scale (VAS): Participants assessed the severity of their pain using a 100 mm visual analog scale (VAS). The scale ranged from 0 (no pain) to 100 (worst possible pain), measurement on a scale corresponds to the magnitude of their pain.

Outcome measures

Outcome measures
Measure	Placebo n=184 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=184 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=181 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=186 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Change From Baseline in Pain Visual Analogue Scale (VAS) Scores at Week 14	-10.30 mm Standard Error 1.67	-12.86 mm Standard Error 1.66	-17.75 mm Standard Error 1.69	-11.74 mm Standard Error 1.66

SECONDARY outcome

Timeframe: Week 14

Acetaminophen (up to 4 gram/day as needed for pain relief) was an allowable concomitant medication as a rescue therapy. The total daily acetaminophen dose taken during double-blind treatment was calculated for each participant as: (total acetaminophen dose during the study) divided by (total number of study days).

Outcome measures

Outcome measures
Measure	Placebo n=184 Participants Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=184 Participants Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=182 Participants Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=186 Participants Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Total Daily Acetaminophen Dose	460.65 mg/day Standard Error 125.43	449.14 mg/day Standard Error 124.79	508.53 mg/day Standard Error 126.71	724.42 mg/day Standard Error 124.72

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 97 other events

Deaths: 0 deaths

Pregabalin 300 mg

Serious events: 2 serious events

Other events: 137 other events

Deaths: 0 deaths

Pregabalin 450 mg

Serious events: 8 serious events

Other events: 141 other events

Deaths: 0 deaths

Pregabalin 600 mg

Serious events: 4 serious events

Other events: 154 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Organization: Pfizer, Inc.

Phone: 800-718-1021

Email: [email protected]

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 mo 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

Measure	Placebo n=184 participants at risk Placebo matched to pregabalin capsules orally twice daily up to Week 14.	Pregabalin 300 mg n=184 participants at risk Pregabalin capsule 150 milligram (mg) orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily and Day 4 onwards: 150 mg orally twice daily fixed dose up to Week 14.	Pregabalin 450 mg n=182 participants at risk Pregabalin capsule 225 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12 onwards: 225 mg orally twice daily fixed dose up to Week 14.	Pregabalin 600 mg n=186 participants at risk Pregabalin capsule 300 mg orally twice daily following a 2 week titration phase, Day 1-3: 75 mg orally twice daily, Day 4-8: 150 mg orally twice daily, Day 9-11: 200 mg orally twice daily and Day 12-14: 225 mg orally twice daily and then 300 mg orally twice daily fixed dose up to Week 14.
Ear and labyrinth disorders Vertigo	2.2% 4/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.1% 13/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.6% 12/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.1% 15/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vision blurred	0.54% 1/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 6/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.9% 9/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.0% 13/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	4.3% 8/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.8% 18/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.6% 12/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.1% 15/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	6.5% 12/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.8% 7/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 6/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.3% 8/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	2.2% 4/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.7% 16/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.0% 20/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.8% 20/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	10.9% 20/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.0% 22/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 6/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.5% 12/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	8.2% 15/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.6% 14/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.3% 26/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 17/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	3.8% 7/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.3% 19/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.2% 15/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.5% 27/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Influenza	3.3% 6/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.7% 5/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.8% 7/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.4% 10/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	3.8% 7/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.8% 7/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.5% 10/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.2% 6/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Weight increased	3.3% 6/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.0% 24/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.2% 24/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.9% 24/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	4.3% 8/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.4% 10/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 6/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.7% 5/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Disturbance in attention	2.2% 4/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.4% 10/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.6% 12/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.1% 15/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	15.2% 28/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	37.0% 68/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	41.8% 76/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 93/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	16.3% 30/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.7% 27/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.7% 25/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.6% 16/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Somnolence	6.0% 11/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	20.1% 37/184 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.2% 24/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	18.3% 34/186 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.