Trial Outcomes & Findings for Polysomnography Study Of Pregabalin And Pramipexole Versus Placebo In Patients With Restless Legs Syndrome And Associated Sleep Disturbance (NCT NCT00991276)

Last Updated: 2021-02-15

Results Overview

WASO as determined by Polysomnography (PSG) was time spent awake from sleep onset to final awakening. WASO= Wake Time During Sleep \[WTDS\] epochs + Wake Time After Sleep \[WTAS\] epochs)/2. WTDS: number of wake epochs (30 seconds of PSG recording) after onset of persistent sleep and prior to final awakening or end of 8-hour recording/2 and WTAS: number of wake epochs after final awakening until end of the 8-hour recording/2. WASO was measured on 2 consecutive days within a period. Arithmetic mean of WASO of each participant for all periods was taken prior to employing linear mixed model.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

85 participants

Primary outcome timeframe

Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or Early Termination (ET)

Results posted on

2021-02-15

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Then Pramipexole 0.5 mg Then Pregabalin 300 mg Placebo (PBO) capsule matched to pramipexole (PPX) 0.5 milligram (mg) once daily or pregabalin (PGB) 300 mg once daily (matching placebo escalation and tapering scheme was followed) in first intervention period then PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in second intervention period and PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pramipexole 0.5 mg Then Pregabalin 300 mg Then Placebo PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in first intervention period then PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in second intervention period and PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pregabalin 300 mg Then Placebo Then Pramipexole 0.5 mg PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in first intervention period then PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in second intervention period and PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pregabalin 300 mg Then Pramipexole 0.5 mg Then Placebo PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in first intervention period then PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in second intervention period and PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Placebo Then Pregabalin 300 mg Then Pramipexole 0.5 mg PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in first intervention period then PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in second intervention period and PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pramipexole 0.5 mg Then Placebo Then Pregabalin 300 mg PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in first intervention period then PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in second intervention period and PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.
First Intervention Period STARTED	15	13	14	15	15	13
First Intervention Period COMPLETED	15	10	14	11	11	12
First Intervention Period NOT COMPLETED	0	3	0	4	4	1
Placebo Wash-out Period (7 Days) STARTED	14	8	14	9	10	11
Placebo Wash-out Period (7 Days) COMPLETED	14	8	14	9	10	11
Placebo Wash-out Period (7 Days) NOT COMPLETED	0	0	0	0	0	0
Second Intervention Period STARTED	15	10	14	11	11	12
Second Intervention Period COMPLETED	14	8	14	9	10	11
Second Intervention Period NOT COMPLETED	1	2	0	2	1	1
Third Intervention Period STARTED	14	8	14	9	10	11
Third Intervention Period COMPLETED	13	8	13	8	10	10
Third Intervention Period NOT COMPLETED	1	0	1	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Then Pramipexole 0.5 mg Then Pregabalin 300 mg Placebo (PBO) capsule matched to pramipexole (PPX) 0.5 milligram (mg) once daily or pregabalin (PGB) 300 mg once daily (matching placebo escalation and tapering scheme was followed) in first intervention period then PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in second intervention period and PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pramipexole 0.5 mg Then Pregabalin 300 mg Then Placebo PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in first intervention period then PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in second intervention period and PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pregabalin 300 mg Then Placebo Then Pramipexole 0.5 mg PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in first intervention period then PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in second intervention period and PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pregabalin 300 mg Then Pramipexole 0.5 mg Then Placebo PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in first intervention period then PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in second intervention period and PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Placebo Then Pregabalin 300 mg Then Pramipexole 0.5 mg PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in first intervention period then PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in second intervention period and PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pramipexole 0.5 mg Then Placebo Then Pregabalin 300 mg PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in first intervention period then PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in second intervention period and PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.
First Intervention Period Adverse Event	0	1	0	1	0	0
First Intervention Period Protocol Violation	0	0	0	0	2	0
First Intervention Period Insufficient clinical response	0	0	0	0	1	0
First Intervention Period Other	0	0	0	1	1	0
First Intervention Period Withdrawal by Subject	0	1	0	1	0	1
First Intervention Period Lost to Follow-up	0	1	0	1	0	0
Second Intervention Period Adverse Event	0	2	0	1	1	0
Second Intervention Period Protocol Violation	1	0	0	0	0	0
Second Intervention Period Other	0	0	0	1	0	1
Third Intervention Period Protocol Violation	1	0	0	0	0	0
Third Intervention Period Other	0	0	0	0	0	1
Third Intervention Period Adverse Event	0	0	1	0	0	0
Third Intervention Period Withdrawal by Subject	0	0	0	1	0	0

Baseline Characteristics

Polysomnography Study Of Pregabalin And Pramipexole Versus Placebo In Patients With Restless Legs Syndrome And Associated Sleep Disturbance

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Then Pramipexole 0.5 mg Then Pregabalin 300 mg n=15 Participants Placebo (PBO) capsule matched to pramipexole (PPX) 0.5 milligram (mg) once daily or pregabalin (PGB) 300 mg once daily (matching placebo escalation and tapering scheme was followed) in first intervention period then PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in second intervention period and PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pramipexole 0.5 mg Then Pregabalin 300 mg Then Placebo n=13 Participants PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in first intervention period then PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in second intervention period and PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pregabalin 300 mg Then Placebo Then Pramipexole 0.5 mg n=14 Participants PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in first intervention period then PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in second intervention period and PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pregabalin 300 mg Then Pramipexole 0.5 mg Then Placebo n=15 Participants PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in first intervention period then PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in second intervention period and PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Placebo Then Pregabalin 300 mg Then Pramipexole 0.5 mg n=15 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in first intervention period then PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in second intervention period and PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Pramipexole 0.5 mg Then Placebo Then Pregabalin 300 mg n=13 Participants PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in first intervention period then PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in second intervention period and PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period.	Total n=85 Participants Total of all reporting groups
Age, Customized Less than 18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants
Age, Customized 18 to 44 years	3 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants	5 participants n=21 Participants	3 participants n=8 Participants	18 participants n=8 Participants
Age, Customized 45 to 64 years	8 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants	10 participants n=4 Participants	8 participants n=21 Participants	8 participants n=8 Participants	52 participants n=8 Participants
Age, Customized Greater than or equal to 65 years	4 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	2 participants n=21 Participants	2 participants n=8 Participants	15 participants n=8 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	12 Participants n=21 Participants	7 Participants n=8 Participants	54 Participants n=8 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	3 Participants n=21 Participants	6 Participants n=8 Participants	31 Participants n=8 Participants

PRIMARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or Early Termination (ET)

Population: Intent to Treat (ITT) population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Wake After Sleep Onset (WASO)	51.50 minutes Interval 43.2 to 59.79	78.42 minutes Interval 70.34 to 86.51	78.60 minutes Interval 70.29 to 86.9

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least one post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.

PLMAI, as determined by PSG was number of periodic limb movements leading to arousal per hour (per hour of Total Sleep Time \[TST\]). Arithmetic mean of PLMAI of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Periodic Limb Movement Arousal Index (PLMAI)	3.93 movement/hour Interval 2.49 to 5.36	2.66 movement/hour Interval 1.27 to 4.06	7.61 movement/hour Interval 6.17 to 9.04

SECONDARY outcome

Timeframe: Week 3 and Week 5 of Each Intervention Period or ET

Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.

sTST as derived from Subjective Sleep Questionnaire (SSQ), a participant reported subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. Completed by the participant 30 minutes after waking; recall period is the night before. Arithmetic mean of sTST of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=72 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=70 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Subjective Total Sleep Time (sTST)	400.97 minutes Interval 386.36 to 415.58	374.19 minutes Interval 360.0 to 388.37	370.16 minutes Interval 355.69 to 384.63

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

Minutes of Stage 1 Non-Rapid Eye Movement (Non-REM) sleep (Stage N1), Stage 2 Non-REM sleep (Stage N2), Stage 3 Non-REM sleep (Stage N3) or Slow Wave Sleep (SWS) and Stage REM (Stage R) sleep, as determined by PSG were calculated as total number of Stage N1 30-second (30-sec) epochs divided by 2, total number of Stage N2 30-sec epochs divided by 2, total number of Stage N3 30-sec epochs divided by 2 and total number of Stage R 30-sec epochs divided by 2 respectively. Arithmetic mean of minutes of stage N1, N2, N3 and R sleep of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Minutes of Stage N1, N2, N3 and R Sleep Stage N1 Sleep	38.06 minutes Interval 32.97 to 43.14	48.38 minutes Interval 43.38 to 53.38	43.72 minutes Interval 38.63 to 48.81
Minutes of Stage N1, N2, N3 and R Sleep Stage N2 Sleep	227.05 minutes Interval 215.01 to 239.09	241.52 minutes Interval 229.76 to 253.27	204.35 minutes Interval 192.29 to 216.4
Minutes of Stage N1, N2, N3 and R Sleep Stage N3 Sleep/SWS	66.88 minutes Interval 57.78 to 75.98	34.78 minutes Interval 25.87 to 43.69	45.95 minutes Interval 36.85 to 55.06
Minutes of Stage N1, N2, N3 and R Sleep Stage R Sleep	70.40 minutes Interval 64.32 to 76.48	51.80 minutes Interval 45.86 to 57.75	75.37 minutes Interval 69.29 to 81.45

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

NAASO1, as determined by PSG, was the number of times there was a wake period of at least 1 epoch from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage 2 Non-REM \[Stage N2\] 30-second (30-sec) epoch, Stage 3 Non-REM \[Stage N3\] 30-sec epoch, or stage rapid eye movement \[stage R\] 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO1 of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1)	18.43 awakenings Interval 16.49 to 20.36	26.30 awakenings Interval 24.41 to 28.19	21.10 awakenings Interval 19.16 to 23.04

SECONDARY outcome

Timeframe: Week 3 and Week 5 of Each Intervention Period or ET

RLS-NDI:participant-rated instrument to assess daytime performance and participant's previous night's sleep, consists of 14 items encompassing 5 domains:tiredness;emotional functioning;social functioning;cognitive functioning;activities of daily living and 1 global item for overall well-being. Each item: 0-10 scale; 0=Not at all; 10=Extremely. Total score: sum of scores from question 1-14 (question 10, 11: scores reversed). Total score range: 0-140; higher scores: more severe impact. Arithmetic mean of RLS-NDI of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=72 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=70 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Restless Legs Syndrome-Next Day Impact (RLS-NDI)	41.43 units on a scale Interval 35.36 to 47.5	46.33 units on a scale Interval 40.39 to 52.27	46.78 units on a scale Interval 40.75 to 52.81

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

PLMI, as determined by PSG was number of periodic limb movements per hour based on time in bed (TIB). Arithmetic mean of PLMI of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Periodic Limb Movement Index (PLMI)	25.45 movement/hour Interval 20.99 to 29.91	14.11 movement/hour Interval 9.79 to 18.42	39.95 movement/hour Interval 35.48 to 44.41

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

PLMSI, as determined by PSG was number of periodic limb movements in sleep per hour based on TST. Arithmetic mean of PLMSI of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Periodic Limb Movement in Sleep Index (PLMSI)	22.42 movement/hour Interval 17.46 to 27.39	8.00 movement/hour Interval 3.2 to 12.8	36.95 movement/hour Interval 31.99 to 41.92

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

NAASO2, as determined by PSG, was the number of times there was a wake period of at least 2 30-sec epochs from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO2 of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Number of Awakenings of at Least 2 Epochs After Sleep Onset (NAASO2)	7.68 awakenings Interval 6.55 to 8.82	12.39 awakenings Interval 11.28 to 13.5	10.55 awakenings Interval 9.42 to 11.68

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

NASO, as determined by PSG, was calculated as number of times there is a shift from a stage N2 to N3 or R 30-sec epoch to a stage N1 30-sec epoch from the onset of persistent sleep to light on. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NASO of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Number of Arousals (NASO)	17.84 arousals Interval 15.06 to 20.61	24.19 arousals Interval 21.47 to 26.9	20.29 arousals Interval 17.51 to 23.06

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

Arousal index, as determined by PSG, was NASO per hours of sleep from the onset of persistent sleep to light on. Arithmetic mean of NASOI of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Arousal Index (NASOI)	2.75 arousals/hour Interval 2.23 to 3.28	4.18 arousals/hour Interval 3.67 to 4.69	3.44 arousals/hour Interval 2.92 to 3.96

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

IRLS: psychometrically; clinically valid; clinician-administered instrument assesses severity of RLS. RLS symptom severity and impact on daily living comprise of 10 items giving 2 subscale scores and 1 global score. Subscale scores: symptom severity(6 items) and impact on daily living(3 items), item 3 loaded equally on both subscales. Global score calculated from 10 items. Score of all items range from 0-4, total score range:0-40. Lower scores: lower severity and better quality of life. Arithmetic mean of IRLS of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=68 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=70 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=69 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
International Restless Legs Syndrome Study Group Rating Scale (IRLS)	12.28 units on a scale Interval 10.32 to 14.24	15.35 units on a scale Interval 13.42 to 17.28	18.38 units on a scale Interval 16.42 to 20.34

SECONDARY outcome

Timeframe: Baseline, Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

CGI-I: 7-point clinician rated scale to assess improvement in disease condition as compared to the start of the study medication (baseline), ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved). Higher score = more affected.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=70 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=69 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Percentage of Participants With Response to Clinical Global Impression - Improvement (CGI-I) Scale	61.2 percentage of participants	50.0 percentage of participants	33.3 percentage of participants

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

LREM, as determined by PSG, was number of non-wake epochs from the beginning of the recording to the first occurrence of Stage R sleep divided by 2. Arithmetic mean of LREM of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Latency to Stage R Sleep (LREM)	95.22 minutes Interval 82.11 to 108.33	130.99 minutes Interval 118.26 to 143.72	84.52 minutes Interval 71.4 to 97.64

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

LPS, as determined by PSG, was number of epochs from the beginning of the recording ("lights-out") to the start of the first 20 consecutive non-wake epochs (10 minutes of persistent sleep) divided by 2. Arithmetic mean of LPS of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Latency to Persistent Sleep (LPS)	31.13 minutes Interval 22.06 to 40.19	31.52 minutes Interval 22.68 to 40.36	38.86 minutes Interval 29.78 to 47.93

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

WTDS, as determined by PSG, was the number of wake (30-sec) epochs after the onset of persistent sleep and prior to the final awakening or at the end of 8-hour recording. WTDS was the sum of 2 consecutive days of recordings divided by 2 at the end of each intervention period. Arithmetic mean of WTDS of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Wake Time During Sleep (WTDS)	45.77 minutes Interval 37.81 to 53.73	70.51 minutes Interval 62.77 to 78.25	69.75 minutes Interval 61.78 to 77.72

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

WTAS, as determined by PSG, was the number of wake (30-sec) epochs after the final awakening until the end of the 8-hour recording. WTAS was the sum of 2 consecutive days of recordings divided by 2 at the end of each intervention period. Arithmetic mean of WTAS of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Wake Time After Sleep (WTAS)	5.58 minutes Interval 2.15 to 9.0	7.86 minutes Interval 4.53 to 11.19	8.88 minutes Interval 5.45 to 12.3

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

TST, as determined by PSG, was the number of non-wake (30-sec) epochs from the beginning of recording to the end of the recording. TST was the sum of 2 consecutive days of recording divided by 2 at the end of each intervention period. Arithmetic mean of TST of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Total Sleep Time (TST)	402.38 minutes Interval 390.6 to 414.15	376.52 minutes Interval 364.99 to 388.05	369.66 minutes Interval 357.88 to 381.44

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

SE, as determined by PSG, was the TST divided by the time in bed (TIB)(both in minutes), multiplied by 100. Sum of 2 consecutive days of recording divided by 2 at the end of each intervention period. Arithmetic mean of SE of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Sleep Efficiency (SE)	83.81 Percentage of time asleep Interval 81.36 to 86.27	78.58 Percentage of time asleep Interval 76.17 to 80.98	77.02 Percentage of time asleep Interval 74.56 to 79.48

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. Here "n" signifies number of participants analyzed at that particular time point for each arm group respectively.

WASO, as determined by PSG was time spent awake from sleep onset to final awakening. WASO = (sum of WTDS 30-sec epochs and WTAS 30-sec epochs)/2, measured on 2 consecutive days at end of each intervention period by each individual hour (8 hours total) and each individual quarter of night (eight hours in 2 hour increments). Arithmetic mean of WASO of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=73 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=76 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=72 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Quarter 4 (n= 67, 71, 68)	22.37 minutes Interval 17.7 to 27.04	29.55 minutes Interval 25.0 to 34.1	30.21 minutes Interval 25.54 to 34.89
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Hour 1 (n= 66, 67, 66)	1.62 minutes 95% Confidence Interval 4.12 • Interval 0.7 to 2.54	2.26 minutes 95% Confidence Interval 2.69 • Interval 1.35 to 3.17	3.35 minutes 95% Confidence Interval 3.84 • Interval 2.41 to 4.28
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Hour 2 (n= 67, 70, 66)	5.04 minutes 95% Confidence Interval 6.15 • Interval 3.54 to 6.53	7.07 minutes 95% Confidence Interval 5.48 • Interval 5.61 to 8.53	7.39 minutes 95% Confidence Interval 6.85 • Interval 5.86 to 8.93
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Hour 3 (n= 67, 70, 67)	4.89 minutes Interval 3.14 to 6.64	8.23 minutes Interval 6.52 to 9.93	8.90 minutes Interval 7.13 to 10.68
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Hour 4 (n= 67, 70, 68)	6.21 minutes Interval 4.29 to 8.13	11.54 minutes Interval 9.67 to 13.42	9.52 minutes Interval 7.59 to 11.44
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Hour 5 (n= 67, 70, 68)	5.93 minutes Interval 3.8 to 8.06	10.39 minutes Interval 8.32 to 12.46	10.04 minutes Interval 7.91 to 12.17
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Hour 6 (n= 67, 71, 68)	5.78 minutes Interval 3.49 to 8.08	10.54 minutes Interval 8.32 to 12.76	10.52 minutes Interval 8.22 to 12.81
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Hour 7 (n= 67, 71, 68)	9.18 minutes Interval 6.72 to 11.64	11.44 minutes Interval 9.06 to 13.82	12.09 minutes Interval 9.63 to 14.55
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Hour 8 (n= 67, 71, 68)	13.16 minutes Interval 10.09 to 16.23	18.27 minutes Interval 15.28 to 21.25	18.15 minutes Interval 15.08 to 21.22
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Quarter 1 (n= 67, 70, 66)	6.42 minutes Interval 4.59 to 8.26	8.99 minutes Interval 7.2 to 10.78	10.35 minutes Interval 8.47 to 12.23
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Quarter 2 (n= 67, 70, 68)	11.08 minutes Interval 8.09 to 14.07	19.77 minutes Interval 16.86 to 22.69	18.18 minutes Interval 15.19 to 21.17
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) Quarter 3 (n= 67, 71, 68)	11.81 minutes Interval 8.03 to 15.59	20.77 minutes Interval 17.11 to 24.42	20.55 minutes Interval 16.77 to 24.33

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

NAASO1, as determined by PSG, was the number of times there was a wake period of at least 1 30-sec epoch from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NAASO1 of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=73 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=76 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=72 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Hour 1 (n= 66, 67, 66)	0.70 awakenings 95% Confidence Interval 0.90 • Interval 0.47 to 0.93	1.39 awakenings 95% Confidence Interval 1.12 • Interval 1.16 to 1.62	1.10 awakenings 95% Confidence Interval 0.76 • Interval 0.87 to 1.34
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Hour 2 (n= 67, 70, 66)	2.06 awakenings 95% Confidence Interval 1.41 • Interval 1.68 to 2.44	3.32 awakenings 95% Confidence Interval 1.74 • Interval 2.96 to 3.69	2.47 awakenings 95% Confidence Interval 1.44 • Interval 2.09 to 2.86
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Hour 3 (n= 67, 70, 67)	2.09 awakenings Interval 1.69 to 2.48	3.42 awakenings Interval 3.03 to 3.81	2.66 awakenings Interval 2.25 to 3.06
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Hour 4 (n= 67, 70, 68)	2.44 awakenings Interval 2.0 to 2.88	3.83 awakenings Interval 3.4 to 4.25	2.71 awakenings Interval 2.27 to 3.15
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Hour 5 (n= 67, 70, 68)	2.47 awakenings Interval 2.06 to 2.89	3.76 awakenings Interval 3.36 to 4.17	2.87 awakenings Interval 2.46 to 3.29
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Hour 6 (n= 67, 71, 68)	2.91 awakenings Interval 2.46 to 3.36	3.68 awakenings Interval 3.24 to 4.12	3.16 awakenings Interval 2.71 to 3.62
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Hour 7 (n= 67, 71, 68)	3.07 awakenings Interval 2.62 to 3.53	4.04 awakenings Interval 3.6 to 4.47	3.32 awakenings Interval 2.87 to 3.77
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Hour 8 (n= 67, 71, 68)	2.76 awakenings Interval 2.3 to 3.21	3.46 awakenings Interval 3.02 to 3.9	3.11 awakenings Interval 2.65 to 3.56
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Quarter 1 (n= 67, 70, 66)	2.71 awakenings Interval 2.22 to 3.2	4.61 awakenings Interval 4.13 to 5.09	3.49 awakenings Interval 2.98 to 3.99
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Quarter 2 (n= 67, 70, 68)	4.53 awakenings Interval 3.86 to 5.21	7.27 awakenings Interval 6.61 to 7.93	5.32 awakenings Interval 4.64 to 5.99
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Quarter 3 (n= 67, 71, 68)	5.39 awakenings Interval 4.66 to 6.12	7.37 awakenings Interval 6.66 to 8.08	6.04 awakenings Interval 5.31 to 6.77
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) Quarter 4 (n= 67, 71, 68)	5.87 awakenings Interval 5.15 to 6.59	7.36 awakenings Interval 6.67 to 8.06	6.44 awakenings Interval 5.73 to 7.16

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

NAASO2, as determined by PSG, was the number of times there was a wake period of at least 2 30-sec epochs from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NAASO2 of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=73 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=76 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=72 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Hour 5 (n= 67, 70, 68)	1.06 awakenings Interval 0.81 to 1.31	1.76 awakenings Interval 1.52 to 2.01	1.48 awakenings Interval 1.22 to 1.73
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Hour 6 (n= 67, 71, 68)	1.02 awakenings Interval 0.79 to 1.26	1.57 awakenings Interval 1.34 to 1.8	1.44 awakenings Interval 1.2 to 1.68
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Hour 7 (n= 67, 71, 68)	1.24 awakenings Interval 0.97 to 1.51	1.94 awakenings Interval 1.68 to 2.2	1.57 awakenings Interval 1.3 to 1.84
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Hour 8 (n= 67, 71, 68)	1.00 awakenings Interval 0.75 to 1.24	1.56 awakenings Interval 1.32 to 1.79	1.28 awakenings Interval 1.04 to 1.52
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Quarter 1 (n= 67, 70, 66)	1.43 awakenings Interval 1.11 to 1.75	2.27 awakenings Interval 1.96 to 2.58	2.06 awakenings Interval 1.73 to 2.38
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Quarter 2 (n= 67, 70, 68)	1.99 awakenings Interval 1.58 to 2.39	3.56 awakenings Interval 3.16 to 3.96	2.85 awakenings Interval 2.44 to 3.26
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Quarter 3 (n= 67, 71, 68)	2.10 awakenings Interval 1.68 to 2.51	3.30 awakenings Interval 2.89 to 3.7	2.92 awakenings Interval 2.5 to 3.34
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Quarter 4 (n= 67, 71, 68)	2.25 awakenings Interval 1.86 to 2.64	3.44 awakenings Interval 3.06 to 3.82	2.86 awakenings Interval 2.47 to 3.25
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Hour 3 (n= 67, 70, 67)	0.99 awakenings Interval 0.75 to 1.23	1.71 awakenings Interval 1.48 to 1.95	1.41 awakenings Interval 1.17 to 1.65
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Hour 4 (n= 67, 70, 68)	1.01 awakenings Interval 0.74 to 1.27	1.84 awakenings Interval 1.58 to 2.09	1.48 awakenings Interval 1.22 to 1.74
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Hour 1 (n= 66, 67, 66)	0.42 awakenings 95% Confidence Interval 0.60 • Interval 0.26 to 0.58	0.61 awakenings 95% Confidence Interval 0.71 • Interval 0.45 to 0.76	0.73 awakenings 95% Confidence Interval 0.59 • Interval 0.57 to 0.89
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) Hour 2 (n= 67, 70, 66)	1.04 awakenings 95% Confidence Interval 0.83 • Interval 0.79 to 1.29	1.72 awakenings 95% Confidence Interval 1.13 • Interval 1.48 to 1.96	1.37 awakenings 95% Confidence Interval 1.06 • Interval 1.12 to 1.63

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

NASO, as determined by PSG was the number of times there is a shift from a stage N2 to N3 or R 30-sec epoch to a stage N1 30-sec epoch from the onset of persistent sleep to light on. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NASO for each participant at each period was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=73 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=76 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=72 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Hourly and Quarterly Assessment of Number of Arousals (NASO) Hour 1 (n= 66, 67, 66)	1.48 arousals 95% Confidence Interval 1.65 • Interval 1.01 to 1.94	2.06 arousals 95% Confidence Interval 2.22 • Interval 1.6 to 2.52	1.79 arousals 95% Confidence Interval 1.78 • Interval 1.32 to 2.26
Hourly and Quarterly Assessment of Number of Arousals (NASO) Hour 2 (n= 67, 70, 66)	2.36 arousals 95% Confidence Interval 2.03 • Interval 1.85 to 2.86	3.23 arousals 95% Confidence Interval 2.15 • Interval 2.74 to 3.72	2.68 arousals 95% Confidence Interval 1.99 • Interval 2.16 to 3.19
Hourly and Quarterly Assessment of Number of Arousals (NASO) Hour 3 (n= 67, 70, 67)	2.31 arousals Interval 1.75 to 2.87	3.23 arousals Interval 2.68 to 3.78	2.80 arousals Interval 2.23 to 3.37
Hourly and Quarterly Assessment of Number of Arousals (NASO) Hour 4 (n= 67, 70, 68)	2.94 arousals Interval 2.39 to 3.49	3.41 arousals Interval 2.88 to 3.94	2.76 arousals Interval 2.22 to 3.31
Hourly and Quarterly Assessment of Number of Arousals (NASO) Hour 5 (n= 67, 70, 68)	2.33 arousals Interval 1.76 to 2.9	3.20 arousals Interval 2.64 to 3.75	2.89 arousals Interval 2.32 to 3.46
Hourly and Quarterly Assessment of Number of Arousals (NASO) Hour 6 (n= 67, 71, 68)	2.39 arousals Interval 1.88 to 2.9	3.30 arousals Interval 2.8 to 3.8	2.70 arousals Interval 2.19 to 3.22
Hourly and Quarterly Assessment of Number of Arousals (NASO) Hour 7 (n= 67, 71, 68)	2.15 arousals Interval 1.67 to 2.63	3.28 arousals Interval 2.81 to 3.75	2.66 arousals Interval 2.18 to 3.14
Hourly and Quarterly Assessment of Number of Arousals (NASO) Hour 8 (n= 67, 71, 68)	2.07 arousals Interval 1.56 to 2.57	2.98 arousals Interval 2.49 to 3.46	2.46 arousals Interval 1.96 to 2.97
Hourly and Quarterly Assessment of Number of Arousals (NASO) Quarter 1 (n= 67, 70, 66)	3.75 arousals Interval 2.93 to 4.57	5.09 arousals Interval 4.28 to 5.89	4.26 arousals Interval 3.43 to 5.09
Hourly and Quarterly Assessment of Number of Arousals (NASO) Quarter 2 (n= 67, 70, 68)	5.25 arousals Interval 4.32 to 6.18	6.67 arousals Interval 5.76 to 7.57	5.55 arousals Interval 4.62 to 6.48
Hourly and Quarterly Assessment of Number of Arousals (NASO) Quarter 3 (n= 67, 71, 68)	4.75 arousals Interval 3.86 to 5.64	6.44 arousals Interval 5.58 to 7.3	5.61 arousals Interval 4.72 to 6.5
Hourly and Quarterly Assessment of Number of Arousals (NASO) Quarter 4 (n= 67, 71, 68)	4.23 arousals Interval 3.39 to 5.06	6.24 arousals Interval 5.43 to 7.04	5.13 arousals Interval 4.29 to 5.96

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

Population: ITT population included set of randomized participants who had at least one dose of study medication and had at least one post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.

PLM, as determined by PSG was number of periodic limb movements based on time in bed (TIB). Calculated at each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of PLM of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Hour 1	31.45 movement/hour 95% Confidence Interval 29.70 • Interval 23.6 to 39.3	21.57 movement/hour 95% Confidence Interval 27.03 • Interval 13.96 to 29.18	54.67 movement/hour 95% Confidence Interval 39.98 • Interval 46.81 to 62.53
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Hour 2	26.38 movement/hour 95% Confidence Interval 29.20 • Interval 19.25 to 33.51	12.49 movement/hour 95% Confidence Interval 14.51 • Interval 5.59 to 19.39	52.93 movement/hour 95% Confidence Interval 40.92 • Interval 45.8 to 60.07
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Hour 3	40.93 movement/hour Interval 32.38 to 49.48	14.05 movement/hour Interval 5.77 to 22.32	48.76 movement/hour Interval 40.2 to 57.32
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Hour 4	30.35 movement/hour Interval 23.05 to 37.64	14.50 movement/hour Interval 7.45 to 21.55	46.58 movement/hour Interval 39.29 to 53.88
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Hour 5	25.70 movement/hour Interval 19.02 to 32.38	11.93 movement/hour Interval 5.47 to 18.38	36.17 movement/hour Interval 29.49 to 42.86
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Hour 6	21.02 movement/hour Interval 15.01 to 27.04	10.57 movement/hour Interval 4.75 to 16.38	32.47 movement/hour Interval 26.45 to 38.49
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Hour 7	14.22 movement/hour Interval 9.06 to 19.37	11.11 movement/hour Interval 6.12 to 16.09	27.04 movement/hour Interval 21.88 to 32.2
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Hour 8	13.37 movement/hour Interval 8.54 to 18.2	16.55 movement/hour Interval 11.86 to 21.24	20.97 movement/hour Interval 16.14 to 25.81
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Quarter 1	57.82 movement/hour Interval 44.51 to 71.12	34.02 movement/hour Interval 21.14 to 46.91	107.56 movement/hour Interval 94.24 to 120.87
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Quarter 2	71.29 movement/hour Interval 56.94 to 85.64	28.55 movement/hour Interval 14.66 to 42.43	95.31 movement/hour Interval 80.95 to 109.67
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Quarter 3	46.77 movement/hour Interval 35.42 to 58.11	22.49 movement/hour Interval 11.51 to 33.46	68.66 movement/hour Interval 57.3 to 80.01
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) Quarter 4	27.60 movement/hour Interval 18.97 to 36.24	27.64 movement/hour Interval 19.28 to 36.0	48.01 movement/hour Interval 39.36 to 56.65

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

SE, as determined by PSG, was the TST divided by the time in bed (TIB)(both in minutes), multiplied by 100. Sum of 2 consecutive days of recording divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean for SE of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=68 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Hour 3	90.22 percentage of time asleep Interval 86.68 to 93.77	84.86 percentage of time asleep Interval 81.43 to 88.29	81.86 percentage of time asleep Interval 78.32 to 85.4
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Hour 1	62.31 percentage of time asleep 95% Confidence Interval 24.14 • Interval 56.62 to 68.01	66.88 percentage of time asleep 95% Confidence Interval 24.30 • Interval 61.33 to 72.43	57.80 percentage of time asleep 95% Confidence Interval 22.90 • Interval 52.1 to 63.49
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Hour 2	86.13 percentage of time asleep 95% Confidence Interval 16.94 • Interval 81.85 to 90.41	83.43 percentage of time asleep 95% Confidence Interval 16.03 • Interval 79.26 to 87.6	77.31 percentage of time asleep 95% Confidence Interval 20.49 • Interval 73.03 to 81.6
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Hour 4	89.41 percentage of time asleep Interval 85.86 to 92.97	79.84 percentage of time asleep Interval 76.4 to 83.28	82.61 percentage of time asleep Interval 79.05 to 86.16
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Hour 5	90.00 percentage of time asleep Interval 86.3 to 93.7	81.85 percentage of time asleep Interval 78.27 to 85.43	82.92 percentage of time asleep Interval 79.22 to 86.63
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Hour 6	90.33 percentage of time asleep Interval 86.45 to 94.21	81.64 percentage of time asleep Interval 77.88 to 85.39	82.49 percentage of time asleep Interval 78.61 to 86.38
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Hour 7	84.70 percentage of time asleep Interval 80.6 to 88.8	80.90 percentage of time asleep Interval 76.92 to 84.87	79.86 percentage of time asleep Interval 75.76 to 83.96
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Hour 8	78.07 percentage of time asleep Interval 72.95 to 83.19	69.51 percentage of time asleep Interval 64.53 to 74.5	69.75 percentage of time asleep Interval 64.63 to 74.88
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Quarter 3	90.09 percentage of time asleep Interval 86.83 to 93.34	81.74 percentage of time asleep Interval 78.59 to 84.9	82.75 percentage of time asleep Interval 79.49 to 86.01
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Quarter 4	81.37 percentage of time asleep Interval 77.45 to 85.28	75.16 percentage of time asleep Interval 71.35 to 78.97	74.84 percentage of time asleep Interval 70.93 to 78.76
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Quarter 1	74.21 percentage of time asleep Interval 69.69 to 78.73	75.15 percentage of time asleep Interval 70.73 to 79.57	67.62 percentage of time asleep Interval 63.1 to 72.15
Hourly and Quarterly Assessment of Sleep Efficiency (SE) Quarter 2	89.84 percentage of time asleep Interval 86.77 to 92.92	82.37 percentage of time asleep Interval 79.38 to 85.35	82.30 percentage of time asleep Interval 79.23 to 85.38

SECONDARY outcome

Timeframe: Week 3 and Week 5 of Each Intervention Period or ET

SSQ: participant-rated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items giving 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This (1 item) subscale: numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0 awakenings to 30 awakenings. Lower value indicates better quality of sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=72 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=70 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale	1.69 awakenings Interval 1.34 to 2.03	2.64 awakenings Interval 2.31 to 2.98	2.51 awakenings Interval 2.17 to 2.86

SECONDARY outcome

Timeframe: Week 3 and Week 5 of each intervention period or ET

SSQ: participant-rated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This 1 item subscale (in minutes): numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0-1440 minutes. Lower value: better sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=65 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=70 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Subjective Sleep Questionnaire (SSQ): Total Wake Time After Sleep Onset Subscale	53.78 minutes Interval 42.94 to 64.61	82.23 minutes Interval 71.76 to 92.7	79.09 minutes Interval 68.46 to 89.72

SECONDARY outcome

Timeframe: Week 3 and Week 5 of each intervention period or ET

SSQ: participant-rated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This 1 item subscale: numerical rating completed by participant 30 minutes after waking; recall period: night before, Range: 0 to 100, higher score: better quality of sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=72 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=70 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale	6.74 units on a scale Interval 6.35 to 7.13	5.69 units on a scale Interval 5.31 to 6.06	5.70 units on a scale Interval 5.32 to 6.08

SECONDARY outcome

Timeframe: Week 3 and Week 5 of each intervention period or ET

SSQ: participant-rated instrument assesses sleep behavior; measures sleep quantity, quality. Comprised of 5 items giving 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. Latency (time to fall asleep \[in minutes\]): numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0 - 840 minutes, lower value: better sleep. Arithmetic mean of subscale score of each participant for all periods was taken prior to employing linear mixed model. Hours of sleep subscale results reported as sTST.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=67 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=72 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=70 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Subjective Sleep Questionnaire (SSQ): Latency Subscale	42.49 minutes Interval 34.26 to 50.72	40.59 minutes Interval 32.52 to 48.66	50.07 minutes Interval 41.89 to 58.25

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. Here "n" signifies number of participants analyzed for particular subscale for each arm group respectively.

MOS-SS:Participant rated instrument, assesses sleep quantity, quality;with 12 items(7 subscale scores:sleep disturbance, snoring, awakening short of breath/with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep;2 composite index scores:sleep problems Index I, II). Subscale scores total range:0-100(except sleep quantity\[range 0-24 hours\], optimal sleep\[range 0-1: 0= \<7 or \>8 hours;1=7/8 hours\]). Higher scores=poorer sleep outcomes(except sleep quantity, adequacy). Arithmetic mean of MOS-SS scores of each participant for all periods was taken before linear mixed model analysis.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=73 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=76 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=72 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Medical Outcomes Study - Sleep Scale (MOS-SS) Awaken Short of Breath/with Headache (n= 68,71,69)	11.59 units on a scale Interval 6.2 to 16.97	13.10 units on a scale Interval 7.77 to 18.44	10.88 units on a scale Interval 5.49 to 16.27
Medical Outcomes Study - Sleep Scale (MOS-SS) Adequacy (n= 68,71,69)	54.96 units on a scale Interval 48.11 to 61.81	43.90 units on a scale Interval 37.21 to 50.58	40.79 units on a scale Interval 33.93 to 47.65
Medical Outcomes Study - Sleep Scale (MOS-SS) Somnolence (n= 68,71,69)	21.28 units on a scale Interval 17.08 to 25.47	21.32 units on a scale Interval 17.21 to 25.44	23.71 units on a scale Interval 19.51 to 27.9
Medical Outcomes Study - Sleep Scale (MOS-SS) Sleep Quantity (n= 68,71,69)	6.43 units on a scale Interval 5.95 to 6.91	6.50 units on a scale Interval 6.03 to 6.97	5.97 units on a scale Interval 5.49 to 6.46
Medical Outcomes Study - Sleep Scale (MOS-SS) 9-Item Sleep Problems Index (n= 68,71,69)	32.75 units on a scale Interval 28.06 to 37.44	37.88 units on a scale Interval 33.28 to 42.47	42.89 units on a scale Interval 38.2 to 47.59
Medical Outcomes Study - Sleep Scale (MOS-SS) Optimal Sleep (n= 68,71,69)	0.43 units on a scale Interval 0.32 to 0.54	0.35 units on a scale Interval 0.24 to 0.46	0.29 units on a scale Interval 0.18 to 0.4
Medical Outcomes Study - Sleep Scale (MOS-SS) Sleep Disturbance (n= 68,71,69)	34.08 units on a scale Interval 28.11 to 40.06	40.19 units on a scale Interval 34.34 to 46.04	48.65 units on a scale Interval 42.66 to 54.63
Medical Outcomes Study - Sleep Scale (MOS-SS) Snoring (n= 67,71,68)	15.27 units on a scale Interval 10.05 to 20.49	15.97 units on a scale Interval 10.86 to 21.08	17.96 units on a scale Interval 12.75 to 23.17
Medical Outcomes Study - Sleep Scale (MOS-SS) 6-Item Sleep Problems Index (n= 68,71,69)	30.69 units on a scale Interval 25.94 to 35.45	37.24 units on a scale Interval 32.58 to 41.89	40.59 units on a scale Interval 35.83 to 45.34

SECONDARY outcome

Timeframe: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET

RLS-QoL: psychometrically and clinically valid and reliable participant-rated instrument, assesses impact of RLS on participant quality of life. Specifically, it assessed effects of RLS on health status function (symptom severity, daily activity, social functioning, sleep, concentrating and decision making, travelling, sexual activity, and work) giving a summary score ranging from 0-100. Higher scores reflect better quality of life. Recall period: 1 week prior to assessment. Arithmetic mean of RLS-QoL score of each participant for all periods was taken prior to employing linear mixed model.

Outcome measures

Outcome measures
Measure	Pregabalin 300 mg n=68 Participants PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=71 Participants PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=69 Participants PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
Restless Leg Syndrome - Quality of Life Scale (RLS-QoL)	73.30 units on a scale Interval 69.72 to 76.87	70.05 units on a scale Interval 66.53 to 73.56	68.03 units on a scale Interval 64.45 to 71.61

Adverse Events

Pregabalin 300 mg

Serious events: 2 serious events

Other events: 46 other events

Deaths: 0 deaths

Pramipexole 0.5 mg

Serious events: 1 serious events

Other events: 40 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pregabalin 300 mg n=75 participants at risk PGB capsule 300 mg once daily in any intervention period.	Pramipexole 0.5 mg n=76 participants at risk PPX capsule 0.5 mg once daily in any intervention period.	Placebo n=73 participants at risk PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in any of the intervention period.
Infections and infestations Gastroenteritis	0.00% 0/75 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	0.00% 0/76 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	1.4% 1/73 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.
Investigations Blood pressure orthostatic decreased	1.3% 1/75 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	0.00% 0/76 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	0.00% 0/73 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/75 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	0.00% 0/76 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	1.4% 1/73 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.
Nervous system disorders Dizziness postural	1.3% 1/75 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	0.00% 0/76 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	0.00% 0/73 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.
Psychiatric disorders Suicidal ideation	0.00% 0/75 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	1.3% 1/76 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	1.4% 1/73 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.
Vascular disorders Deep vein thrombosis	1.3% 1/75 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	0.00% 0/76 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.	0.00% 0/73 The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of 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.
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