Trial Outcomes & Findings for A 17-Week Trial To Assess Pregabalin For The Treatment Of Nerve Pain Due To Spinal Cord Injury (NCT NCT00407745)

Results Overview

DAAC was derived from participant's daily pain diary, where pain was measured on an 11-point Numerical Rating Scale (NRS-Pain)ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]). The DAAC was calculated as the mean of all daily pain diary rating post baseline minus the baseline score then multiplied by the proportion of the planned study duration completed by the participant.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

220 participants

Primary outcome timeframe

Baseline, Week 16

Results posted on

2021-01-25

Participant Flow

1 participant was randomized after the first dose of study drug was taken; the participant was randomized to placebo, but the actual drug taken was pregabalin. This partcipant was included in the placebo group for all baseline characteristics and efficacy outcome measures; and in the pregabalin group for overall study and adverse events reporting.

Participant milestones

Participant milestones
Measure	Pregabalin Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo Placebo matching study treatment.
Overall Study STARTED	112	108
Overall Study Treated	112	107
Overall Study COMPLETED	93	91
Overall Study NOT COMPLETED	19	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo Placebo matching study treatment.
Overall Study Lack of Efficacy	1	2
Overall Study Withdrawal by Subject	3	3
Overall Study Protocol Violation	5	3
Overall Study Adverse Event	8	8
Overall Study Other	2	0
Overall Study Randomized, unknown if treated	0	1

Baseline Characteristics

A 17-Week Trial To Assess Pregabalin For The Treatment Of Nerve Pain Due To Spinal Cord Injury

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin n=111 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=108 Participants Placebo matching study treatment.	Total n=219 Participants Total of all reporting groups
Age, Continuous	46.1 years STANDARD_DEVIATION 12.7 • n=99 Participants	45.6 years STANDARD_DEVIATION 13.8 • n=107 Participants	45.9 years STANDARD_DEVIATION 13.3 • n=206 Participants
Age, Customized Between 18 and 44 years	52 participants n=99 Participants	53 participants n=107 Participants	105 participants n=206 Participants
Age, Customized Between 45 and 64 years	50 participants n=99 Participants	45 participants n=107 Participants	95 participants n=206 Participants
Age, Customized >= 65 years	9 participants n=99 Participants	10 participants n=107 Participants	19 participants n=206 Participants
Sex: Female, Male Female	27 Participants n=99 Participants	16 Participants n=107 Participants	43 Participants n=206 Participants
Sex: Female, Male Male	84 Participants n=99 Participants	92 Participants n=107 Participants	176 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: mITT: all randomized participants who received at least one dose of study medication except the 8 participants who were randomized before protocol amendment 2.

DAAC was derived from participant's daily pain diary, where pain was measured on an 11-point Numerical Rating Scale (NRS-Pain)ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]). The DAAC was calculated as the mean of all daily pain diary rating post baseline minus the baseline score then multiplied by the proportion of the planned study duration completed by the participant.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Duration Adjusted Average Change (DAAC) of Mean Pain Score	-1.66 score on scale Standard Error 0.157	-1.07 score on scale Standard Error 0.149

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; modified baseline observation carried forward (mBOCF) imputation: mBOCF mean pain score was defined as the baseline mean pain score for participants who discontinued double-blind treatment due to adverse event or who had no postbaseline observations and as the last observation carried forward (LOCF) mean pain score for all other participants.

Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Weekly Mean Pain Score Baseline	6.5 score on scale Standard Deviation 1.45	6.5 score on scale Standard Deviation 1.41
Change From Baseline in Weekly Mean Pain Score Change from baseline at endpoint	-1.9 score on scale Standard Deviation 1.91	-1.2 score on scale Standard Deviation 1.78

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF: LOCF Endpoint corresponded to the last 7 days of diary data up to and including Week 16 and applied if the Week 16 assessment was missing; (N) = number of participants that can be analyzed for the endpoint.

Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=105 Participants Placebo matching study treatment.
Number of Participants With >=30% Reduction in Weekly Mean Pain Score From Baseline	48 participants	33 participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (N) = number of participants with data available for analysis

The PGIC is a participant-rated instrument measuring change in the participant's overall status on a 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse.

Outcome measures

Outcome measures
Measure	Pregabalin n=100 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=99 Participants Placebo matching study treatment.
Number of Participants With Categorical Scores on the Patient Global Impression of Change (PGIC) (Full Scale) 1-Very much improved	7 participants	2 participants
Number of Participants With Categorical Scores on the Patient Global Impression of Change (PGIC) (Full Scale) 2-Much improved	33 participants	25 participants
Number of Participants With Categorical Scores on the Patient Global Impression of Change (PGIC) (Full Scale) 3-Minimally improved	38 participants	24 participants
Number of Participants With Categorical Scores on the Patient Global Impression of Change (PGIC) (Full Scale) 4-No change	19 participants	40 participants
Number of Participants With Categorical Scores on the Patient Global Impression of Change (PGIC) (Full Scale) 5-Minimally worse	2 participants	5 participants
Number of Participants With Categorical Scores on the Patient Global Impression of Change (PGIC) (Full Scale) 6-Much worse	0 participants	3 participants
Number of Participants With Categorical Scores on the Patient Global Impression of Change (PGIC) (Full Scale) 7-Very much worse	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Weekly Mean Sleep Interference Score Baseline (n = 105, 105)	4.9 score on scale Standard Deviation 2.48	5.2 score on scale Standard Deviation 2.24
Change From Baseline in Weekly Mean Sleep Interference Score Change from baseline at endpoint (n = 105, 104)	-2.0 score on scale Standard Deviation 2.35	-1.0 score on scale Standard Deviation 1.77

SECONDARY outcome

Timeframe: Baseline, Week 1 through16

Population: ITT population: defined as all randomized participants who took at least one dose of study medication. (This population included the 8 participants who were randomized before the protocol amendment 2). (n) = number of participants with data for analysis.

Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=111 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=108 Participants Placebo matching study treatment.
Change From Baseline in Weekly Mean Pain Score by Week Baseline (n = 111, 108)	6.44 score on scale Standard Deviation 1.44	6.51 score on scale Standard Deviation 1.40
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 1 (n = 111, 107)	-0.85 score on scale Standard Deviation 1.04	-0.38 score on scale Standard Deviation 0.89
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 2 (n = 110, 105)	-1.26 score on scale Standard Deviation 1.21	-0.62 score on scale Standard Deviation 1.30
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 3 (n = 107, 105)	-1.35 score on scale Standard Deviation 1.35	-0.86 score on scale Standard Deviation 1.35
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 4 (n = 107, 103)	-1.64 score on scale Standard Deviation 1.61	-1.03 score on scale Standard Deviation 1.53
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 5 (n = 105, 101)	-1.87 score on scale Standard Deviation 1.73	-1.07 score on scale Standard Deviation 1.50
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 6 (n = 105, 99)	-1.89 score on scale Standard Deviation 1.90	-1.22 score on scale Standard Deviation 1.72
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 7 (n = 103, 98)	-2.02 score on scale Standard Deviation 1.86	-1.34 score on scale Standard Deviation 1.75
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 8 (n = 101, 97)	-1.96 score on scale Standard Deviation 1.82	-1.32 score on scale Standard Deviation 1.82
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 9 (n = 98, 97)	-1.99 score on scale Standard Deviation 1.81	-1.37 score on scale Standard Deviation 1.75
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 10 (n = 97, 91)	-2.03 score on scale Standard Deviation 1.75	-1.32 score on scale Standard Deviation 1.81
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 11 (n = 96, 90)	-2.04 score on scale Standard Deviation 1.82	-1.43 score on scale Standard Deviation 1.84
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 12 (n = 96, 91)	-1.90 score on scale Standard Deviation 1.83	-1.44 score on scale Standard Deviation 1.93
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 13 (n = 93, 91)	-2.02 score on scale Standard Deviation 1.76	-1.39 score on scale Standard Deviation 1.92
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 14 (n = 93, 92)	-2.00 score on scale Standard Deviation 1.76	-1.34 score on scale Standard Deviation 1.89
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 15 (n = 93, 92)	-2.09 score on scale Standard Deviation 1.80	-1.41 score on scale Standard Deviation 1.85
Change From Baseline in Weekly Mean Pain Score by Week Change at Week 16 (n = 89, 90)	-2.17 score on scale Standard Deviation 1.78	-1.36 score on scale Standard Deviation 1.87

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (N) = number of participants with data available for analysis

Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=105 Participants Placebo matching study treatment.
Number of Participants With >=50% Reduction in Weekly Mean Pain Score From Baseline	31 participants	16 participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

The Modified Brief Pain Inventory (mBPI-10) Interference Scale is a self administered questionnaire that assessed pain interference with functional activities over the past week. The items were measured on an 11 point scale, ranging from "does not interfere" (0) to "completely interferes" (10). A composite score, the pain interference index, was calculated by averaging the 10 items that comprised the scale.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Modified Brief Pain Inventory Interference Scale (10-Item) (mBPI-10) Total Score Baseline	4.7 score on scale Standard Deviation 2.18	4.9 score on scale Standard Deviation 2.21
Change From Baseline in Modified Brief Pain Inventory Interference Scale (10-Item) (mBPI-10) Total Score Change from baseline at endpoint (n = 100, 99)	-1.6 score on scale Standard Deviation 2.19	-1.1 score on scale Standard Deviation 2.02

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated pain scale. The pain produced by the applied stimulus (static mechanical allodynia - gentle constant mechanical pressure) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP) - Static Mechanical Allodynia Baseline (n = 83, 82)	2.9 score on scale Standard Deviation 3.16	2.6 score on scale Standard Deviation 2.95
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP) - Static Mechanical Allodynia Change from baseline at endpoint (n = 79, 75)	-1.0 score on scale Standard Deviation 2.69	-0.3 score on scale Standard Deviation 2.48

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated pain scale. The pain produced by the applied stimulus (dynamic mechanical allodynia - gentle stroking with foam brush) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP) - Dynamic Mechanical Allodynia Baseline (n = 83, 82)	2.7 score on scale Standard Deviation 2.81	2.3 score on scale Standard Deviation 2.84
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP) - Dynamic Mechanical Allodynia Change from baseline at endpoint (n = 79, 75)	-0.6 score on scale Standard Deviation 2.35	-0.3 score on scale Standard Deviation 2.32

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated pain scale. The pain produced by the applied stimulus (Punctata hyperalgesia - pinprick) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Punctata Hyperalgesia Baseline (n=83,82)	3.9 score on scale Standard Deviation 3.41	3.4 score on scale Standard Deviation 3.19
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Punctata Hyperalgesia Change from baseline at endpoint (n=79,75)	-1.0 score on scale Standard Deviation 2.36	-0.4 score on scale Standard Deviation 2.15

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated pain scale. The pain produced by the applied stimulus (Temporal summation to tactile stimuli - repeated touching/tapping) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Temporal Summation to Tactile Stimuli Baseline (n = 83, 82)	4.1 score on scale Standard Deviation 3.54	3.9 score on scale Standard Deviation 3.48
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Temporal Summation to Tactile Stimuli Change from baseline at endpoint (n = 79, 75)	-0.5 score on scale Standard Deviation 2.21	-0.8 score on scale Standard Deviation 2.37

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated pain scale. The pain produced by the applied stimulus (Cold allodynia - touch with cool metal rod 13-17 degrees celsius was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Cold Allodynia Baseline (n = 83, 82)	2.5 score on scale Standard Deviation 2.97	2.7 score on scale Standard Deviation 3.13
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Cold Allodynia Change from baseline at endpoint (n = 79, 72)	-0.1 score on scale Standard Deviation 2.12	0.4 score on scale Standard Deviation 2.66

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated pain scale. The pain produced by the applied stimulus (Cold hyperalgesia - touch with cold metal rod 4 degrees celsius) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain).

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Cold Hyperalgesia Subscales Baseline (n = 83, 82)	2.8 score on scale Standard Deviation 3.18	2.8 score on scale Standard Deviation 3.25
Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Cold Hyperalgesia Subscales Change from baseline at endpoint (n = 79, 72)	-0.1 score on scale Standard Deviation 2.60	0.4 score on scale Standard Deviation 2.82

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - 12 Items Total Intensity Score Baseline (n = 104, 106)	0.4 score on scale Standard Deviation 0.20	0.4 score on scale Standard Deviation 0.22
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - 12 Items Total Intensity Score Change from baseline at endpoint (n = 99, 99)	-0.1 score on scale Standard Deviation 0.21	-0.1 score on scale Standard Deviation 0.17

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF;(n) = number of participants with data available for analysis

Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Burning Spontaneous Pain Baseline	0.5 score on scale Standard Deviation 0.32	0.5 score on scale Standard Deviation 0.30
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Burning Spontaneous Pain Change from baseline at endpoint (n = 100, 99)	-0.1 score on scale Standard Deviation 0.34	-0.1 score on scale Standard Deviation 0.28

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Pressing Spontaneous Pain Baseline	0.4 score on scale Standard Deviation 0.31	0.4 score on scale Standard Deviation 0.31
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Pressing Spontaneous Pain Change from baseline at endpoint (n = 100, 99)	-0.1 score on scale Standard Deviation 0.28	-0.0 score on scale Standard Deviation 0.26

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Paroxysmal Pain Baseline	0.4 score on scale Standard Deviation 0.29	0.3 score on scale Standard Deviation 0.30
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Paroxysmal Pain Change from baseline at endpoint (n = 100, 99)	-0.1 score on scale Standard Deviation 0.31	-0.1 score on scale Standard Deviation 0.26

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Evoked Pain Baseline	0.4 score on scale Standard Deviation 0.29	0.4 score on scale Standard Deviation 0.29
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Evoked Pain Change from baseline at endpoint (n = 100, 99)	-0.1 score on scale Standard Deviation 0.24	-0.1 score on scale Standard Deviation 0.22

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Paresthesia/Dysesthesia Baseline (n = 104, 106)	0.5 score on scale Standard Deviation 0.28	0.5 score on scale Standard Deviation 0.28
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Paresthesia/Dysesthesia Change from baseline at endpoint (n = 99, 99)	-0.1 score on scale Standard Deviation 0.29	-0.1 score on scale Standard Deviation 0.27

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire used to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score of 0-100. Higher score indicates a greater intensity of pain.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 1- Burning pain (n = 100, 99)	-1.39 score on scale Standard Deviation 3.420	-1.00 score on scale Standard Deviation 2.825
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 2- Squeezing pain (n = 100, 99)	-1.04 score on scale Standard Deviation 3.181	-0.41 score on scale Standard Deviation 3.110
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 3- Pain like pressure (n = 100, 99)	-0.73 score on scale Standard Deviation 3.429	-0.20 score on scale Standard Deviation 3.326
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 5- Electric shocks (n = 100, 99)	-1.77 score on scale Standard Deviation 3.426	-0.68 score on scale Standard Deviation 3.664
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 6- Stabbing pain (n = 100, 99)	-1.13 score on scale Standard Deviation 3.541	-0.52 score on scale Standard Deviation 2.804
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 8- By light touching (n = 100, 99)	-0.78 score on scale Standard Deviation 3.080	-0.94 score on scale Standard Deviation 2.683
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 9- By pressure (n = 100, 99)	-1.22 score on scale Standard Deviation 2.784	-1.10 score on scale Standard Deviation 2.675
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 10- By something cold (n = 100, 99)	-0.89 score on scale Standard Deviation 3.372	-0.52 score on scale Standard Deviation 2.459
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 11- Pins and needles (n = 99, 99)	-1.01 score on scale Standard Deviation 3.125	-0.62 score on scale Standard Deviation 3.269
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score 12- Tingling (n = 99, 99)	-0.99 score on scale Standard Deviation 3.559	-0.83 score on scale Standard Deviation 3.034

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: MITT; LOCF; (N) = number of participants with data available for analysis

NPSI - Temporal item which assesses the duration (number of hours during the last 24 hours) of spontaneous ongoing pain. Improved duration would be a decrease in the number of hours of spontaneous ongoing pain during the last 24 hours compared to baseline.

Outcome measures

Outcome measures
Measure	Pregabalin n=100 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=97 Participants Placebo matching study treatment.
Number of Participants With Improved Duration of Brief Pain Attacks Based on NPSI - Duration (Item 4)	39 participants	28 participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: MITT; LOCF; (N) = number of participants with data available for analysis

NPSI - Temporal item which assesses the paroxysmal pain (number of pain attacks during the last 24 hours). Improvement in the number of attacks would be a decrease in the number of paroxysms during the last 24 hours compared to baseline.

Outcome measures

Outcome measures
Measure	Pregabalin n=100 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=99 Participants Placebo matching study treatment.
Number of Participants With Improvement in the Number of Attacks Based on NPSI - Number of Attacks (Item 7)	48 participants	38 participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS)- 9-Item Overall Sleep Problems Index Baseline (n = 105, 103)	45.7 score on scale Standard Deviation 18.02	45.9 score on scale Standard Deviation 19.00
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS)- 9-Item Overall Sleep Problems Index Change from baseline at endpoint (n = 100, 95)	-10.8 score on scale Standard Deviation 16.70	-5.8 score on scale Standard Deviation 16.21

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Disturbance Baseline (n = 105, 104)	51.9 score on scale Standard Deviation 25.88	51.2 score on scale Standard Deviation 26.68
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Disturbance Change from baseline at endpoint (n = 100, 97)	-17.3 score on scale Standard Deviation 25.25	-8.0 score on scale Standard Deviation 21.70

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Adequacy Baseline (n = 105, 104)	42.3 score on scale Standard Deviation 25.92	43.8 score on scale Standard Deviation 26.92
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Adequacy Change from baseline at endpoint (n = 100, 97)	11.6 score on scale Standard Deviation 27.26	5.7 score on scale Standard Deviation 28.83

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Snoring Baseline (n = 105, 104)	31.2 score on scale Standard Deviation 34.07	35.6 score on scale Standard Deviation 35.47
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Snoring Change from baseline at endpoint (n = 100, 97)	2.2 score on scale Standard Deviation 25.88	-4.7 score on scale Standard Deviation 27.50

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Awaken Short of Breath or With a Headache Baseline (n = 105, 105)	15.0 score on scale Standard Deviation 23.00	12.8 score on scale Standard Deviation 23.23
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Awaken Short of Breath or With a Headache Change from baseline at endpoint (n = 100, 98)	-6.2 score on scale Standard Deviation 22.33	-0.2 score on scale Standard Deviation 22.52

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Quantity Baseline (n = 104,105)	5.9 score on scale Standard Deviation 1.45	6.2 score on scale Standard Deviation 1.64
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Quantity Change from baseline at endpoint (n = 100, 98)	0.6 score on scale Standard Deviation 1.42	0.2 score on scale Standard Deviation 1.29

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.

Outcome measures

Outcome measures
Measure	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Somnolence Baseline (n = 105, 105)	36.3 score on scale Standard Deviation 19.81	39.7 score on scale Standard Deviation 23.43
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Somnolence Change from baseline at endpoint (n = 100, 97)	-0.8 score on scale Standard Deviation 20.64	-4.9 score on scale Standard Deviation 22.31

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (N) = number of participants with data available for analysis

Participant rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.

Outcome measures

Outcome measures
Measure	Pregabalin n=100 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=99 Participants Placebo matching study treatment.
Number of Participants Having Optimal Sleep Based on Medical Outcomes Study Sleep Scale (MOS-SS)	49 participants	30 participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

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	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Hospital and Anxiety Depression Scale (HADS) - Anxiety Baseline	6.7 score on scale Standard Deviation 4.41	6.9 score on scale Standard Deviation 4.12
Change From Baseline in Hospital and Anxiety Depression Scale (HADS) - Anxiety Change from baseline at endpoint (n = 100, 99)	-1.4 score on scale Standard Deviation 3.21	-0.8 score on scale Standard Deviation 3.55

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: mITT; LOCF; (n) = number of participants with data available for analysis

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	Pregabalin n=105 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=106 Participants Placebo matching study treatment.
Change From Baseline in Hospital and Anxiety Depression Scale (HADS) - Depression Baseline	5.2 score on scale Standard Deviation 3.96	6.3 score on scale Standard Deviation 3.99
Change From Baseline in Hospital and Anxiety Depression Scale (HADS) - Depression Change from baseline at endpoint (n = 100, 99)	-1.0 score on scale Standard Deviation 3.44	-0.5 score on scale Standard Deviation 3.56

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 1 through 16

Population: ITT; (n) = number of participants with data available for analysis

Pain related sleep interference was assessed on an 11 point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]).

Outcome measures

Outcome measures
Measure	Pregabalin n=111 Participants Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=108 Participants Placebo matching study treatment.
Change From Baseline in Weekly Mean Sleep Interference Score by Week Baseline (n = 111, 107)	4.86 score on scale Standard Deviation 2.46	5.18 score on scale Standard Deviation 2.23
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 1 (n = 111, 106)	-0.96 score on scale Standard Deviation 1.45	-0.26 score on scale Standard Deviation 0.85
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 2 (n = 110, 104)	-1.29 score on scale Standard Deviation 1.63	-0.49 score on scale Standard Deviation 1.17
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 3 (n = 107, 104)	-1.36 score on scale Standard Deviation 1.68	-0.61 score on scale Standard Deviation 1.27
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 4 (n = 107, 102)	-1.59 score on scale Standard Deviation 1.85	-0.90 score on scale Standard Deviation 1.45
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 5 (n = 105, 100)	-1.81 score on scale Standard Deviation 2.05	-0.91 score on scale Standard Deviation 1.38
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 6 (n = 105, 98)	-1.86 score on scale Standard Deviation 2.14	-0.99 score on scale Standard Deviation 1.48
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 7 (n = 103, 97)	-1.98 score on scale Standard Deviation 2.19	-1.10 score on scale Standard Deviation 1.50
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 8 (n = 101, 96)	-1.97 score on scale Standard Deviation 2.18	-1.11 score on scale Standard Deviation 1.59
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 9 (n = 98, 96)	-2.03 score on scale Standard Deviation 2.13	-1.11 score on scale Standard Deviation 1.72
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 10 (n = 97, 90)	-2.18 score on scale Standard Deviation 2.06	-1.12 score on scale Standard Deviation 1.74
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 11 (n = 96, 89)	-2.08 score on scale Standard Deviation 2.15	-1.20 score on scale Standard Deviation 1.85
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 12 (n = 96, 90)	-2.07 score on scale Standard Deviation 2.21	-1.20 score on scale Standard Deviation 1.75
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 13 (n = 93, 90)	-2.08 score on scale Standard Deviation 2.21	-1.19 score on scale Standard Deviation 1.82
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 14 (n = 93, 91)	-2.09 score on scale Standard Deviation 2.13	-1.18 score on scale Standard Deviation 1.83
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 15 (n = 93, 91)	-2.15 score on scale Standard Deviation 2.10	-1.11 score on scale Standard Deviation 1.83
Change From Baseline in Weekly Mean Sleep Interference Score by Week Change at Week 16 (n = 89, 89)	-2.25 score on scale Standard Deviation 2.24	-1.17 score on scale Standard Deviation 1.82

Adverse Events

Pregabalin

Serious events: 9 serious events

Other events: 78 other events

Deaths: 0 deaths

Placebo

Serious events: 10 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Pregabalin n=112 participants at risk Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=107 participants at risk Placebo matching study treatment.
Cardiac disorders Bradycardia	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Cardiac disorders Prinzmetal angina	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Ear and labyrinth disorders Ear haemorrhage	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Hepatobiliary disorders Cholecystitis	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Hepatobiliary disorders Cholelithiasis	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Osteomyelitis chronic	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Pneumonia	2.7% 3/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Pyelonephritis acute	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Urinary tract infection	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Injury, poisoning and procedural complications Fall	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Injury, poisoning and procedural complications Head injury	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Injury, poisoning and procedural complications Ulna fracture	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Blood amylase increased	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Metabolism and nutrition disorders Hypoglycaemia	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Back pain	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Muscle spasms	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Pain in extremity	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Periarthritis	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Dystonia	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Renal and urinary disorders Calculus urinary	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Renal and urinary disorders Dysuria	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Renal and urinary disorders Haematuria	0.00% 0/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.93% 1/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Vascular disorders Hypotension	0.89% 1/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.

Measure	Pregabalin n=112 participants at risk Pregabalin 75 milligram (mg) capsule administered by mouth (PO) twice daily (BID) for 7 days. On Day 8, dose may have been maintained at 150 mg per day or increased to 300 mg per day. Each week thereafter, including at Visit 4, a dose increase or decrease may have occurred depending on clinical judgement on adequate pain relief and tolerability. Following the end of adjustment phase, at Visit 4, participants were at their optimized dose (150 mg per day, 300 mg per day, 450 mg per day, or 600 mg per day). Participants remained at this maintenance dose throughout the next 12 weeks of the study.	Placebo n=107 participants at risk Placebo matching study treatment.
Eye disorders Vision blurred	6.2% 7/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	0.00% 0/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	5.4% 6/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	5.6% 6/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	5.4% 6/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	4.7% 5/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	8.0% 9/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	2.8% 3/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	5.4% 6/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	2.8% 3/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	8.9% 10/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	2.8% 3/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	5.4% 6/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	1.9% 2/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	13.4% 15/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	4.7% 5/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Pain	5.4% 6/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	1.9% 2/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	11.6% 13/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	7.5% 8/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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 Urinary tract infection	10.7% 12/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	15.9% 17/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	19.6% 22/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	5.6% 6/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	7.1% 8/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	4.7% 5/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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	33.0% 37/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	13.1% 14/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.
Psychiatric disorders Insomnia	6.2% 7/112 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.	3.7% 4/107 • Baseline up to and including 28 calendar days after the last administration of the study treatment 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.