Trial Outcomes & Findings for Long Term Study Of Pregabalin In Idiopathic Restless Legs Syndrome Patients (NCT NCT00806026)

Last Updated: 2021-01-26

Results Overview

International Restless Legs Syndrome Study Group Rating Scale (IRLS) is psychometrically and clinically valid and reliable clinician-administered instrument used to assess the severity of RLS. It assesses RLS symptom severity and impact on daily living and is comprised of 10 items, scored on 0 to 4 scale, where lower score indicates lower symptom severity/impact on living. Two subscale scores are symptom severity (6 items) ranging from 0-24 (lower score indicates lower symptom severity) and impact on daily living (3 items) ranging from 0-12 (lower score indicates lower impact on living). Item 3 is unrelated to the other items. The global score is calculated from all 10 items, range from 0 to 40, where lower scores reflect lower severity and better quality of life.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

731 participants

Primary outcome timeframe

Baseline

Results posted on

2021-01-26

Participant Flow

Participant milestones

Participant milestones
Measure	Pregabalin 300 mg Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pregabalin 300 mg PBO capsules matched to PGB 300 mg once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) for 12 weeks, re-randomized to PGB 300 mg following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pramipexole 0.25 mg PBO capsules matched to PPX 0.25 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) for 12 weeks, re-randomized to PPX 0.25 mg following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Placebo to Pramipexole 0.5 mg PBO capsules matched to PPX 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) for 12 weeks, re-randomized to PPX 0.5 mg following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Overall Study STARTED	185	183	182	61	59	61
Overall Study Treated	182	178	180	59	59	61
Overall Study COMPLETED	93	82	89	32	29	29
Overall Study NOT COMPLETED	92	101	93	29	30	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin 300 mg Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pregabalin 300 mg PBO capsules matched to PGB 300 mg once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) for 12 weeks, re-randomized to PGB 300 mg following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pramipexole 0.25 mg PBO capsules matched to PPX 0.25 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) for 12 weeks, re-randomized to PPX 0.25 mg following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Placebo to Pramipexole 0.5 mg PBO capsules matched to PPX 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) for 12 weeks, re-randomized to PPX 0.5 mg following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Overall Study Death	0	0	0	1	0	0
Overall Study Did not meet entrance criteria	4	1	2	1	0	0
Overall Study Lack of Efficacy	5	18	13	4	8	7
Overall Study Lost to Follow-up	8	15	8	2	6	6
Overall Study Withdrawal by Subject	14	17	9	2	5	3
Overall Study Other	3	6	8	2	0	4
Overall Study Protocol Violation	6	9	9	0	2	3
Overall Study Adverse Event	52	35	44	17	9	9

Baseline Characteristics

Long Term Study Of Pregabalin In Idiopathic Restless Legs Syndrome Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin 300 mg n=182 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=178 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=180 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pregabalin 300 mg n=59 Participants PBO capsules matched to PGB 300 mg once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) for 12 weeks, re-randomized to PGB 300 mg following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pramipexole 0.25 mg n=59 Participants PBO capsules matched to PPX 0.25 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) for 12 weeks, re-randomized to PPX 0.25 mg following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Placebo to Pramipexole 0.5 mg n=61 Participants PBO capsules matched to PPX 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) for 12 weeks, re-randomized to PPX 0.5 mg following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Total n=719 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=10 Participants	0 Participants n=115 Participants
Age, Customized 18 to 44 years	37 Participants n=5 Participants	34 Participants n=7 Participants	45 Participants n=5 Participants	11 Participants n=4 Participants	17 Participants n=21 Participants	20 Participants n=10 Participants	164 Participants n=115 Participants
Age, Customized 45 to 64 years	101 Participants n=5 Participants	85 Participants n=7 Participants	84 Participants n=5 Participants	29 Participants n=4 Participants	32 Participants n=21 Participants	31 Participants n=10 Participants	362 Participants n=115 Participants
Age, Customized Greater than and equal to 65 years	44 Participants n=5 Participants	59 Participants n=7 Participants	51 Participants n=5 Participants	19 Participants n=4 Participants	10 Participants n=21 Participants	10 Participants n=10 Participants	193 Participants n=115 Participants
Sex: Female, Male Female	123 Participants n=5 Participants	108 Participants n=7 Participants	99 Participants n=5 Participants	37 Participants n=4 Participants	36 Participants n=21 Participants	38 Participants n=10 Participants	441 Participants n=115 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	70 Participants n=7 Participants	81 Participants n=5 Participants	22 Participants n=4 Participants	23 Participants n=21 Participants	23 Participants n=10 Participants	278 Participants n=115 Participants

PRIMARY outcome

Timeframe: Baseline

Population: Intent-to-treat (ITT) population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.

Outcome measures

Outcome measures
Measure	Placebo n=172 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=177 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=169 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=178 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Restless Legs Syndrome (RLS) Symptom Severity	22.40 Units on a Scale Standard Deviation 5.58	22.30 Units on a Scale Standard Deviation 5.73	22.40 Units on a Scale Standard Deviation 5.37	22.10 Units on a Scale Standard Deviation 5.19

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.

IRLS is psychometrically and clinically valid and reliable clinician-administered instrument used to assess the severity of RLS. It assesses RLS symptom severity and impact on daily living and is comprised of 10 items, scored on 0 to 4 scale, where lower score indicates lower symptom severity/impact on living. Two subscale scores are symptom severity (6 items) ranging from 0-24 (lower score indicates lower symptom severity) and impact on daily living (3 items) ranging from 0-12 (lower score indicates lower impact on living). Item 3 is unrelated to the other items. The global score is calculated from all 10 items, range from 0 to 40, where lower scores reflect lower severity and better quality of life.

Outcome measures

Outcome measures
Measure	Placebo n=172 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=177 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=169 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=178 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Change From Baseline in the RLS Symptom Severity at Week 12	-7.30 Units on a Scale Standard Error 0.48	-11.80 Units on a Scale Standard Error 0.47	-7.90 Units on a Scale Standard Error 0.49	-10.50 Units on a Scale Standard Error 0.47

PRIMARY outcome

Timeframe: Week 12

Population: ITT population. Last observation carried forward (LOCF) method was used. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.

CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. Responders were defined as participants who report CGI-I score of "very much improved" or "much improved".

Outcome measures

Outcome measures
Measure	Placebo n=173 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=175 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=168 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=177 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Percentage of Participants Responding to Treatment at Week 12	46.80 Percentage of participants	71.40 Percentage of participants	51.20 Percentage of participants	62.70 Percentage of participants

PRIMARY outcome

Timeframe: Baseline up to Week 52

Augmentation was worsening of RLS symptoms, attributable to a specific long-term therapeutic intervention for RLS. Percentage of participants with augmentation was evaluated by centralized evaluation board using a set of assessment criteria for potential augmentation which included structured interview for diagnosis of augmentation during RLS treatment (SIDA-RLS), augmentation severity rating scale (ASRS), clinical judgment. ASRS measures severity of augmentation and consist of three items to be completed by clinician. Clinician would score participants' answers by comparing post-baseline evaluations to those at baseline. ASRS total score range: 0-24, with higher score indicating more severe augmentation.

Outcome measures

Outcome measures
Measure	Placebo PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=176 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=167 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=178 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Percentage of Participants With Augmentation	—	1.70 Percentage of participants	6.60 Percentage of participants	9.00 Percentage of participants

SECONDARY outcome

Timeframe: Baseline

SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). WASO is time spent awake from sleep onset to final awakening. Total WASO subscale (in minutes): numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Total WASO subscale score ranges from 0-1440 minutes. Lower value indicates better sleep.

Outcome measures

Outcome measures
Measure	Placebo n=163 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=168 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=158 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=169 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Subjective Sleep Questionnaire (SSQ): Subjective Waking After Sleep Onset (WASO)	79.50 minutes Standard Deviation 69.85	90.60 minutes Standard Deviation 76.10	100.20 minutes Standard Deviation 85.92	83.90 minutes Standard Deviation 77.35

SECONDARY outcome

Timeframe: Baseline, Week 12

Outcome measures

Outcome measures
Measure	Placebo n=163 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=168 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=158 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=169 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Change From Baseline in SSQ: Subjective WASO at Week 12	-32.61 minutes Standard Error 3.10	-49.86 minutes Standard Error 3.06	-33.69 minutes Standard Error 3.15	-37.18 minutes Standard Error 3.04

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.

SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Latency subscale (in minutes): numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Latency subscale score ranges from 0-840 minutes. Lower value indicates better sleep.

Outcome measures

Outcome measures
Measure	Placebo n=165 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=169 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=161 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=174 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Subjective Sleep Questionnaire (SSQ): Latency Subscale Score at Week 12	47.70 minutes Standard Deviation 44.89	41.60 minutes Standard Deviation 35.76	43.10 minutes Standard Deviation 35.84	35.90 minutes Standard Deviation 33.08

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.

SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Hours of sleep subscale: numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Hours of sleep subscale score ranges from 0-16 hours. Higher value indicates better sleep.

Outcome measures

Outcome measures
Measure	Placebo n=165 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=170 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=161 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=174 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Subjective Sleep Questionnaire (SSQ): Hours of Sleep Subscale Score at Week 12	6.70 hours Standard Deviation 1.16	7.00 hours Standard Deviation 1.05	6.70 hours Standard Deviation 1.19	6.80 hours Standard Deviation 1.09

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.

SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Number of awakenings subscale: numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Number of awakenings subscale score ranges from 0-30. Lower value indicates better sleep.

Outcome measures

Outcome measures
Measure	Placebo n=165 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=170 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=161 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=174 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale Score at Week 12	1.80 awakenings Standard Deviation 2.14	1.10 awakenings Standard Deviation 1.14	1.70 awakenings Standard Deviation 1.22	1.50 awakenings Standard Deviation 1.08

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.

SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Quality of sleep subscale: numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Quality of sleep subscale score ranges from 0-100. Higher score indicates better quality of sleep.

Outcome measures

Outcome measures
Measure	Placebo n=165 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=170 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=161 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=174 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale Score at Week 12	57.70 Units on a scale Standard Deviation 20.27	66.50 Units on a scale Standard Deviation 20.00	57.40 Units on a scale Standard Deviation 19.83	60.20 Units on a scale Standard Deviation 19.43

SECONDARY outcome

Timeframe: Baseline

The RLS-NDI is a participant-rated instrument designed to assess daytime performance as related to RLS and the participant's previous night's sleep. The instrument consists of 14 items that encompass 5 domains: tiredness; emotional functioning; social functioning; cognitive functioning; and activities of daily living. There is also 1 global item assessing overall well -being. Each item is scored on a 0-10 numeric rating scale. Total score is the sum of scores from question 1 to 14. The total score ranges from 0 to 140 where higher scores indicate a more severe impact.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=26 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=30 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=34 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
RLS-Next Day Impact (RLS-NDI)	50.00 Units on a Scale Standard Deviation 22.64	49.30 Units on a Scale Standard Deviation 22.03	51.90 Units on a Scale Standard Deviation 18.62	58.40 Units on a Scale Standard Deviation 20.27

SECONDARY outcome

Timeframe: Baseline, Week 12

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=26 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=30 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=34 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Change From Baseline in RLS-NDI at Week 12	-6.60 Units on a Scale Standard Error 2.68	-8.10 Units on a Scale Standard Error 2.88	-4.30 Units on a Scale Standard Error 2.65	-14.50 Units on a Scale Standard Error 2.50

SECONDARY outcome

Timeframe: Baseline

100 millimeter (mm) line (Visual Analog Scale) marked by participant. Intensity of pain range (over past week): 0 mm = no pain to 100 mm = worst possible pain.

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=163 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=155 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=167 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Limb Pain-Visual Analog Scale (Limb Pain-VAS)	4.10 mm Standard Deviation 2.52	4.20 mm Standard Deviation 2.70	4.30 mm Standard Deviation 2.58	4.00 mm Standard Deviation 2.53

SECONDARY outcome

Timeframe: Baseline, Week 12

100 mm line (VAS) marked by participant. Intensity of pain range (over past week): 0 mm = no pain to 100 mm = worst possible pain. Change = observation mean minus baseline mean.

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=163 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=155 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=167 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Change From Baseline in Limb Pain-VAS at Week 12	-2.20 mm Standard Error 0.20	-3.20 mm Standard Error 0.20	-2.64 mm Standard Error 0.20	-2.75 mm Standard Error 0.21

SECONDARY outcome

Timeframe: Week 12

ASRS measures severity of augmentation and consist of three items to be completed by clinician. Clinician would score participants' answers by comparing post-baseline evaluations to those at baseline. ASRS total score range: 0-24, with higher score indicating more severe augmentation.

Outcome measures

Outcome measures
Measure	Placebo n=170 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=176 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=167 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=177 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Severity of Augmentation Symptoms at Week 12	1.40 Units on a Scale Standard Deviation 1.95	0.90 Units on a Scale Standard Deviation 1.60	1.60 Units on a Scale Standard Deviation 2.29	1.30 Units on a Scale Standard Deviation 1.87

SECONDARY outcome

Timeframe: Week 12

CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal-not ill at all) to 7 (among the most extremely ill participants). Higher score = more affected.

Outcome measures

Outcome measures
Measure	Placebo n=173 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=176 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=169 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=178 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Clinical Global Impressions-Severity (CGI-S) at Week 12	3.70 Units on a Scale Standard Deviation 1.17	2.90 Units on a Scale Standard Deviation 1.18	3.50 Units on a Scale Standard Deviation 1.22	3.10 Units on a Scale Standard Deviation 1.17

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'n' is signifying those participants who were evaluable for particular category for each group respectively.

MOS-SS: Participant rated instrument to assess sleep quantity, quality; comprised of 12 items yielding 7 subscale scores: sleep disturbance, snoring, awakening short of breath/headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, 2 composite index scores: sleep problems Index I, II. Sleep adequacy data was reported at week 12 and not for first 12 weeks (average). Subscale scores range: 0-100; exception quantity of sleep (range 0-24 hours). With exception of sleep quantity and sleep adequacy, higher scores reflect poorer sleep outcomes.

Outcome measures

Outcome measures
Measure	Placebo n=174 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=177 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=169 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=178 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 Sleep disturbance (n = 175, 169, 178, 171)	38.60 Units on a Scale Standard Deviation 21.43	30.50 Units on a Scale Standard Deviation 21.84	39.30 Units on a Scale Standard Deviation 23.72	34.40 Units on a Scale Standard Deviation 20.89
Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 Sleep adequacy (n = 128, 120, 133, 125 )	50.00 Units on a Scale Standard Deviation 28.74	61.30 Units on a Scale Standard Deviation 28.57	54.80 Units on a Scale Standard Deviation 29.45	55.20 Units on a Scale Standard Deviation 27.87
Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 Sleep problem index II (n = 175, 169, 178, 171)	36.30 Units on a Scale Standard Deviation 16.81	30.70 Units on a Scale Standard Deviation 17.15	36.60 Units on a Scale Standard Deviation 18.90	34.10 Units on a Scale Standard Deviation 17.05
Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 Snoring (n = 172, 169, 178, 170)	24.60 Units on a Scale Standard Deviation 24.57	29.00 Units on a Scale Standard Deviation 27.50	25.80 Units on a Scale Standard Deviation 28.46	25.80 Units on a Scale Standard Deviation 25.81
Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 Awakening short of breath (n = 175, 169, 178, 171)	9.60 Units on a Scale Standard Deviation 15.13	10.50 Units on a Scale Standard Deviation 15.78	12.30 Units on a Scale Standard Deviation 17.09	13.80 Units on a Scale Standard Deviation 18.22
Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 Somnolence (n = 175, 169, 178, 171)	26.00 Units on a Scale Standard Deviation 18.77	23.90 Units on a Scale Standard Deviation 17.57	27.60 Units on a Scale Standard Deviation 18.61	25.50 Units on a Scale Standard Deviation 18.67
Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 Sleep quantity (n = 175, 169, 178, 171)	6.50 Units on a Scale Standard Deviation 1.26	6.80 Units on a Scale Standard Deviation 1.08	6.50 Units on a Scale Standard Deviation 1.25	6.60 Units on a Scale Standard Deviation 1.16
Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 Sleep problem index I (n = 175, 169, 178, 171)	35.00 Units on a Scale Standard Deviation 16.54	29.40 Units on a Scale Standard Deviation 17.26	35.30 Units on a Scale Standard Deviation 18.82	33.40 Units on a Scale Standard Deviation 16.73

SECONDARY outcome

Timeframe: Week 12

MOS-SS: Participant rated instrument to assess sleep quantity, quality; comprised of 12 items yielding 7 subscale scores: sleep disturbance, snoring, awakening short of breath/ headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, 2 composite index scores: sleep problems Index I, II. Optimal sleep subscale scores range: 0-1; Optimal sleep = 1 if 'Average hours sleep' = 7 or 8, is 0 if 'Average hours sleep' is non-missing and less than 7, and is missing if 'Average hours sleep' is missing. Higher scores reflect better sleep outcomes.

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=128 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=120 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=132 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Number of Participants With Medical Outcomes Study-Sleep Scale (MOS-SS)- Optimal Sleep at Week 12	68 Participants	84 Participants	64 Participants	77 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to lack of sufficient knowledge as how to analyze mood data inferentially in RLS population.

POMS are participant-rated instrument comprising 6 sub-scales (tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment) and each subscale comprising 5 items, on 'How you feel right now?' (Scale: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely). All items were rated in the same direction except for vigor-activity. A total score is obtained for each scale. The range of total score is 0 - 100, with higher score indicating more mood disturbance.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 12

RLS QoL: Participant rated instrument used to assess the impact of RLS on quality of life and health status function (symptom severity, daily activity, social functioning, sleep, concentrating and decision making, traveling, sexual activity, and work) yielding a summary score ranging from 0-100. Higher scores reflect better quality of life.

Outcome measures

Outcome measures
Measure	Placebo n=168 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=173 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=169 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=176 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Restless Legs Syndrome-Quality of Life Scale (RLS-QoL) at Week 12	73.23 Units on Scale Standard Deviation 13.98	77.75 Units on Scale Standard Deviation 10.92	73.33 Units on Scale Standard Deviation 13.02	75.48 Units on Scale Standard Deviation 12.69

SECONDARY outcome

Timeframe: Week 12

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health); 2 summary scores (physical and mental component); and self evaluated change in health status (summary of health status). The score for subscale scores and 2 summary score is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Summary of health status is a 5-point Likert scale ranging from "0=much worse now" to "4=much better now". Higher subscale and summary score reflect better health status.

Outcome measures

Outcome measures
Measure	Placebo n=171 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=175 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=168 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=178 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Social functioning	86.80 Units on a Scale Standard Deviation 18.37	87.20 Units on a Scale Standard Deviation 18.01	84.50 Units on a Scale Standard Deviation 18.14	84.00 Units on a Scale Standard Deviation 18.75
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Mental health	78.70 Units on a Scale Standard Deviation 15.23	77.40 Units on a Scale Standard Deviation 16.13	74.60 Units on a Scale Standard Deviation 16.80	76.10 Units on a Scale Standard Deviation 16.29
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Summary mental score	78.00 Units on a Scale Standard Deviation 15.76	78.00 Units on a Scale Standard Deviation 15.73	75.50 Units on a Scale Standard Deviation 15.60	76.10 Units on a Scale Standard Deviation 15.32
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Physical functioning	83.00 Units on a Scale Standard Deviation 19.22	83.70 Units on a Scale Standard Deviation 18.30	81.90 Units on a Scale Standard Deviation 19.56	82.40 Units on a Scale Standard Deviation 19.98
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Role physical	81.50 Units on a Scale Standard Deviation 19.70	81.20 Units on a Scale Standard Deviation 20.75	79.60 Units on a Scale Standard Deviation 19.37	79.10 Units on a Scale Standard Deviation 20.71
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Bodily pain	65.50 Units on a Scale Standard Deviation 20.03	73.30 Units on a Scale Standard Deviation 20.51	65.20 Units on a Scale Standard Deviation 20.14	69.00 Units on a Scale Standard Deviation 20.40
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 General health	72.80 Units on a Scale Standard Deviation 19.47	73.60 Units on a Scale Standard Deviation 18.37	69.80 Units on a Scale Standard Deviation 18.33	70.50 Units on a Scale Standard Deviation 17.68
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Vitality	59.30 Units on a Scale Standard Deviation 20.51	62.40 Units on a Scale Standard Deviation 19.27	59.00 Units on a Scale Standard Deviation 19.69	59.80 Units on a Scale Standard Deviation 20.17
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Role emotional	87.00 Units on a Scale Standard Deviation 18.25	85.10 Units on a Scale Standard Deviation 18.91	83.90 Units on a Scale Standard Deviation 17.77	84.60 Units on a Scale Standard Deviation 18.09
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Summary physical score	75.70 Units on a Scale Standard Deviation 16.03	78.00 Units on a Scale Standard Deviation 16.50	74.20 Units on a Scale Standard Deviation 15.92	75.30 Units on a Scale Standard Deviation 16.43
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 Summary of health status	3.10 Units on a Scale Standard Deviation 0.53	3.10 Units on a Scale Standard Deviation 0.47	3.10 Units on a Scale Standard Deviation 0.49	3.20 Units on a Scale Standard Deviation 0.54

SECONDARY outcome

Timeframe: Week 12

Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'n' is signifying those participants who were evaluable for particular category for each group respectively.

WPAI: 6 question participant rated questionnaire to determine degree to which SHP affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 10 (completely affected/impaired). WPAI outcomes expressed as impairment percentages with higher numbers indicating greater impairment and less productivity.

Outcome measures

Outcome measures
Measure	Placebo n=174 Participants PBO capsules matched to PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg once daily following a two week up escalation for 12 weeks, re-randomized to 1 of the 3 active treatments (PGB 300 mg/ PPX 0.5 mg/ PPX 0.25 mg) and dose was escalated to the assigned fixed dose over 2 weeks and continued up to 40 weeks followed by dose tapering over 1 week similar to the active treatment.	Pregabalin 300 mg n=177 Participants Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=169 Participants Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=178 Participants PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 Overall work (n= 10, 7, 11, 10)	14.60 Percentage of impairment Standard Deviation 23.39	6.00 Percentage of impairment Standard Deviation 9.66	5.70 Percentage of impairment Standard Deviation 11.34	9.10 Percentage of impairment Standard Deviation 20.71
Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 Work time missed (n= 10, 7, 11, 10)	1.50 Percentage of impairment Standard Deviation 3.62	0.00 Percentage of impairment Standard Deviation 0.00	0.00 Percentage of impairment Standard Deviation 0.00	0.00 Percentage of impairment Standard Deviation 0.00
Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 Activity (n= 18, 22, 25, 20)	23.00 Percentage of impairment Standard Deviation 24.52	12.20 Percentage of impairment Standard Deviation 19.27	20.90 Percentage of impairment Standard Deviation 24.28	22.80 Percentage of impairment Standard Deviation 23.01

Adverse Events

Pregabalin 300 mg

Serious events: 9 serious events

Other events: 134 other events

Deaths: 0 deaths

Pramipexole 0.25 mg

Serious events: 12 serious events

Other events: 110 other events

Deaths: 0 deaths

Pramipexole 0.5 mg

Serious events: 9 serious events

Other events: 118 other events

Deaths: 0 deaths

Placebo to Pregabalin 300 mg

Serious events: 5 serious events

Other events: 42 other events

Deaths: 0 deaths

Placebo to Pramipexole 0.25 mg

Serious events: 2 serious events

Other events: 34 other events

Deaths: 0 deaths

Placebo to Pramipexole 0.5 mg

Serious events: 0 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pregabalin 300 mg n=182 participants at risk Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=178 participants at risk Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=180 participants at risk PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pregabalin 300 mg n=59 participants at risk PBO capsules matched to PGB 300 mg once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) for 12 weeks, re-randomized to PGB 300 mg following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pramipexole 0.25 mg n=59 participants at risk PBO capsules matched to PPX 0.25 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) for 12 weeks, re-randomized to PPX 0.25 mg following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Placebo to Pramipexole 0.5 mg n=61 participants at risk PBO capsules matched to PPX 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) for 12 weeks, re-randomized to PPX 0.5 mg following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Cardiac disorders Acute myocardial infarction	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Angina pectoris	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Atrial fibrillation	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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% 0/59 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% 0/59 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% 0/61 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 Bradyarrhythmia	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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% 0/59 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% 0/59 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% 0/61 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Amaurosis fugax	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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% 0/59 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% 0/59 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% 0/61 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 Pancreatitis acute	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Chest pain	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 2/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Device dislocation	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 acute	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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.	1.7% 1/59 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% 0/59 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% 0/61 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 Hepatitis acute	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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.
Immune system disorders Allergy to arthropod sting	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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% 0/59 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% 0/59 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% 0/61 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 Ankle fracture	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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.	1.1% 2/180 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% 0/59 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% 0/59 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% 0/61 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 Fractured coccyx	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Hand fracture	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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% 0/59 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% 0/59 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% 0/61 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 Rib fracture	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Tendon rupture	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Tibia fracture	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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% 0/59 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% 0/59 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% 0/61 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 Wound	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Intervertebral disc protrusion	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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% 0/59 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% 0/59 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% 0/61 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 Osteoarthritis	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Spinal osteoarthritis	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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% 0/59 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% 0/59 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% 0/61 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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.	1.7% 1/59 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% 0/59 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% 0/61 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Carotid artery stenosis	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Cerebrovascular accident	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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.	1.7% 1/59 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% 0/59 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% 0/61 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 Loss of consciousness	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Multiple sclerosis	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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.	1.7% 1/59 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% 0/61 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 Neurological symptom	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Syncope	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Transient ischaemic attack	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Mental status changes	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Suicidal ideation	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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.	1.7% 1/59 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% 0/59 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% 0/61 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 Withdrawal syndrome	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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.	1.7% 1/59 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% 0/59 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% 0/61 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 Bladder dysplasia	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Urinary retention	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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.	0.56% 1/180 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% 0/59 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% 0/59 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% 0/61 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.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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.
Surgical and medical procedures Bladder calculus removal	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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.
Surgical and medical procedures Spinal deformity correction	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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.	1.7% 1/59 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% 0/61 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 Deep vein thrombosis	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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 Hypertension	0.00% 0/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.56% 1/178 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% 0/180 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% 0/59 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% 0/59 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% 0/61 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.

Other adverse events

Other adverse events
Measure	Pregabalin 300 mg n=182 participants at risk Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Pramipexole 0.25 mg n=178 participants at risk Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Pramipexole 0.5 mg n=180 participants at risk PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pregabalin 300 mg n=59 participants at risk PBO capsules matched to PGB 300 mg once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) for 12 weeks, re-randomized to PGB 300 mg following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.	Placebo to Pramipexole 0.25 mg n=59 participants at risk PBO capsules matched to PPX 0.25 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) for 12 weeks, re-randomized to PPX 0.25 mg following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment.	Placebo to Pramipexole 0.5 mg n=61 participants at risk PBO capsules matched to PPX 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) for 12 weeks, re-randomized to PPX 0.5 mg following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment.
Ear and labyrinth disorders Vertigo	7.1% 13/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 2/178 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% 5/180 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.	5.1% 3/59 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% 0/59 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% 0/61 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vision blurred	1.6% 3/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.2% 4/178 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.	0.56% 1/180 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.	5.1% 3/59 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.	1.7% 1/59 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% 0/61 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 Abdominal pain upper	2.7% 5/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.1% 9/178 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% 5/180 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 4/59 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.	1.7% 1/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.9% 3/61 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	7.7% 14/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.7% 3/178 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.	1.1% 2/180 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.5% 5/59 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.	1.7% 1/59 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% 0/61 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	3.8% 7/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.1% 9/178 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% 10/180 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.	3.4% 2/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.5% 5/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.2% 5/61 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	4.9% 9/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.2% 4/178 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.	7.8% 14/180 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.	3.4% 2/59 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.	1.7% 1/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 2/61 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	6.0% 11/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.1% 18/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.4% 26/180 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.	5.1% 3/59 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.	5.1% 3/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.6% 4/61 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 Vomiting	1.6% 3/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.2% 4/178 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% 10/180 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.	5.1% 3/59 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.	3.4% 2/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.2% 5/61 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	12.6% 23/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.7% 19/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.2% 22/180 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.9% 7/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.5% 5/59 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% 8/61 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 Irritability	2.7% 5/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.1% 9/178 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.	1.1% 2/180 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.	3.4% 2/59 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.	1.7% 1/59 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.	1.6% 1/61 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	6.6% 12/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.2% 4/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 6/180 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.	1.7% 1/59 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.	3.4% 2/59 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.	1.6% 1/61 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 Cystitis	1.6% 3/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.2% 4/178 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% 0/180 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.	1.7% 1/59 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.	1.7% 1/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.6% 4/61 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Influenza	4.9% 9/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.3% 13/178 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.	1.7% 3/180 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 4/59 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.	13.6% 8/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.5% 7/61 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	10.4% 19/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.2% 20/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.4% 17/180 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.	5.1% 3/59 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.	5.1% 3/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.8% 9/61 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 Sinusitis	3.3% 6/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.7% 3/178 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.	2.2% 4/180 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 4/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 4/59 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% 0/61 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	3.3% 6/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 2/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 6/180 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.	5.1% 3/59 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.	5.1% 3/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 2/61 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Weight increased	8.8% 16/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.7% 12/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.7% 12/180 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.	3.4% 2/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.9% 7/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.6% 4/61 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	3.8% 7/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.1% 9/178 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.	4.4% 8/180 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.	1.7% 1/59 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.	5.1% 3/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.6% 4/61 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	5.5% 10/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.4% 15/178 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.	7.2% 13/180 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.	3.4% 2/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 4/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.6% 4/61 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 Musculoskeletal pain	2.7% 5/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.2% 4/178 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.	2.2% 4/180 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.	1.7% 1/59 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.	5.1% 3/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 2/61 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	3.8% 7/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.9% 7/178 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.	3.9% 7/180 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 4/59 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.	3.4% 2/59 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.	1.6% 1/61 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 Balance disorder	1.1% 2/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 2/178 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.	0.56% 1/180 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 4/59 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% 0/59 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% 0/61 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	21.4% 39/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.4% 15/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.4% 17/180 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.	16.9% 10/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.2% 6/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.9% 3/61 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	12.1% 22/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	16.9% 30/178 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.	19.4% 35/180 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.	15.3% 9/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.2% 6/59 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.	19.7% 12/61 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 Paraesthesia	2.7% 5/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.2% 4/178 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.	1.7% 3/180 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.	5.1% 3/59 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.	1.7% 1/59 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% 0/61 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	17.6% 32/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.7% 12/178 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.	7.8% 14/180 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.9% 7/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 4/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.2% 5/61 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 Depression	5.5% 10/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.2% 4/178 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.	3.9% 7/180 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.	5.1% 3/59 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.	3.4% 2/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 2/61 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.
Respiratory, thoracic and mediastinal disorders Cough	2.2% 4/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.9% 7/178 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.	3.9% 7/180 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% 0/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.8% 4/59 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.	1.6% 1/61 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 Hypertension	3.8% 7/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.4% 6/178 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.	2.2% 4/180 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.	1.7% 1/59 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.	5.1% 3/59 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 2/61 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 Orthostatic hypotension	0.55% 1/182 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/178 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% 0/180 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.	5.1% 3/59 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% 0/59 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% 0/61 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.

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

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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.
Publication restrictions are in place

Restriction type: OTHER