Trial Outcomes & Findings for Efficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients With Motor Fluctuations (NCT NCT02687542)

NCT ID: NCT02687542

Last Updated: 2020-11-23

Results Overview

A paper Hauser diary was utilized to record motor state for half-hour intervals. Participants completed the diary by answering whether they had been OFF for 3 consecutive days in the week prior to each visit (except Day 28 visit), including 3 consecutive days during the week prior to Day 0 (Randomization). The daily OFF time was calculated as the average of the 3 consecutive daily OFF hours from the Hauser diary at each visit.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 108 participants
• Primary outcome timeframe: Week 10; Baseline was defined as the average daily OFF time (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0).
• Results posted on: 2020-11-23

Participant Flow

Participant milestones

Measure	Placebo The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Overall Study STARTED	23	13	15	13	44
Overall Study COMPLETED	15	1	1	3	24
Overall Study NOT COMPLETED	8	12	14	10	20

Reasons for withdrawal

Measure	Placebo The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Overall Study Medication error without associated AEs	0	0	0	0	1
Overall Study Lost to Follow-up	0	0	0	0	1
Overall Study Protocol Violation	0	1	0	0	0
Overall Study Other	5	9	10	6	5
Overall Study Adverse Event	3	1	3	2	9
Overall Study Withdrawal by Subject	0	1	1	2	4

Baseline Characteristics

Efficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients With Motor Fluctuations

Baseline characteristics by cohort

Measure	Placebo n=23 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	Total n=108 Participants Total of all reporting groups
Age, Continuous	66.04 years STANDARD_DEVIATION 8.79 • n=93 Participants	66.92 years STANDARD_DEVIATION 8.79 • n=4 Participants	63.80 years STANDARD_DEVIATION 7.76 • n=27 Participants	67.77 years STANDARD_DEVIATION 9.36 • n=483 Participants	63.41 years STANDARD_DEVIATION 8.47 • n=36 Participants	64.97 years STANDARD_DEVIATION 8.60 • n=10 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	6 Participants n=4 Participants	6 Participants n=27 Participants	4 Participants n=483 Participants	18 Participants n=36 Participants	40 Participants n=10 Participants
Sex: Female, Male Male	17 Participants n=93 Participants	7 Participants n=4 Participants	9 Participants n=27 Participants	9 Participants n=483 Participants	26 Participants n=36 Participants	68 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants	3 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	3 Participants n=36 Participants	11 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=93 Participants	10 Participants n=4 Participants	13 Participants n=27 Participants	12 Participants n=483 Participants	40 Participants n=36 Participants	95 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants	2 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	1 Participants n=483 Participants	6 Participants n=36 Participants	10 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	1 Participants n=36 Participants	6 Participants n=10 Participants
Race (NIH/OMB) White	20 Participants n=93 Participants	12 Participants n=4 Participants	12 Participants n=27 Participants	9 Participants n=483 Participants	36 Participants n=36 Participants	89 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants	2 Participants n=10 Participants

PRIMARY outcome

Timeframe: Week 10; Baseline was defined as the average daily OFF time (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0).

Population: Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary).

A paper Hauser diary was utilized to record motor state for half-hour intervals. Participants completed the diary by answering whether they had been OFF for 3 consecutive days in the week prior to each visit (except Day 28 visit), including 3 consecutive days during the week prior to Day 0 (Randomization).

The daily OFF time was calculated as the average of the 3 consecutive daily OFF hours from the Hauser diary at each visit.

Outcome measures

Measure	Placebo n=21 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=7 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=41 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Change From Baseline in Daily OFF Time at Week 10	-0.969 Hours Standard Error 0.4092	-1.173 Hours Standard Error 0.3482	-1.316 Hours Standard Error 0.3289	-1.480 Hours Standard Error 0.3460	-1.663 Hours Standard Error 0.4297

SECONDARY outcome

Timeframe: Weeks 3, 5, 10 and 15; Baseline was defined as the average daily OFF time (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0).

Population: Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary).

A paper Hauser diary was utilized to record motor state for half hour intervals. Participants completed the diary by answering whether they had been OFF for 3 consecutive days in the week prior to each visit (except Day 28 visit), including 3 consecutive days during the week prior to Day 0 (Randomization).

The daily OFF time was calculated as the average of the 3 consecutive daily OFF hours from the Hauser diary at each visit.

Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10.

Outcome measures

Measure	Placebo n=21 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=7 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=41 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Change From Baseline in Daily OFF Time Change at Week 3	-0.67 Hours Standard Error 0.620	-0.82 Hours Standard Error 1.237	-0.55 Hours Standard Error 1.091	-1.82 Hours Standard Error 1.182	-1.01 Hours Standard Error 0.464
Change From Baseline in Daily OFF Time Change at Week 5	-0.63 Hours Standard Error 0.490	-2.04 Hours Standard Error 1.054	-2.23 Hours Standard Error 0.964	-1.41 Hours Standard Error 0.937	-1.24 Hours Standard Error 0.392
Change From Baseline in Daily OFF Time Change at Week 10	-0.99 Hours Standard Error 0.628	-0.60 Hours Standard Error 1.423	-1.00 Hours Standard Error 1.508	-2.07 Hours Standard Error 1.187	-1.63 Hours Standard Error 0.502
Change From Baseline in Daily OFF Time Change at Week 15	1.05 Hours Standard Error 1.063	-0.67 Hours Standard Error 2.960	-2.75 Hours Standard Error 2.936	-1.09 Hours Standard Error 1.687	-2.47 Hours Standard Error 0.793

SECONDARY outcome

Timeframe: Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time with Troublesome Dyskinesia (using 3 Hauser patient diary Days) prior to Day -1 (study derived day and equalled to nominal visit Day 0).

Population: Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary).

A paper Hauser diary was utilized to record motor state for half hour intervals. The participants answered the Hauser diary on whether they had been ON with troublesome dyskinesia. A diary day started with the interval 24:00-0:30 through 23:30-24:00 on each chronological day for 3 consecutive days. On the days recording the home diary, participants made an entry every 30 minutes during their normal waking time and upon awakening from time asleep.

The daily ON hours was calculated as the average of the 3 consecutive daily ON hours from the Hauser diary at each visit.

Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10.

Outcome measures

Measure	Placebo n=21 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=7 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=41 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Change From Baseline in Daily ON Time With Troublesome Dyskinesia Change at Week 3	0.17 Hours Standard Error 0.236	0.07 Hours Standard Error 0.467	0.19 Hours Standard Error 0.417	0.01 Hours Standard Error 0.464	0.23 Hours Standard Error 0.179
Change From Baseline in Daily ON Time With Troublesome Dyskinesia Change at Week 5	0.23 Hours Standard Error 0.198	-0.21 Hours Standard Error 0.415	-0.02 Hours Standard Error 0.388	0.45 Hours Standard Error 0.363	0.03 Hours Standard Error 0.162
Change From Baseline in Daily ON Time With Troublesome Dyskinesia Change at Week 10	0.13 Hours Standard Error 0.191	0.24 Hours Standard Error 0.464	0.32 Hours Standard Error 0.529	-0.39 Hours Standard Error 0.389	0.13 Hours Standard Error 0.167
Change From Baseline in Daily ON Time With Troublesome Dyskinesia Change at Week 15	0.01 Hours Standard Error 0.642	-0.43 Hours Standard Error 1.349	-0.29 Hours Standard Error 1.263	0.54 Hours Standard Error 1.071	-0.21 Hours Standard Error 0.463

SECONDARY outcome

Timeframe: Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time without Troublesome Dyskinesia (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit Day 0)

Population: Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary).

A paper Hauser diary was utilized to record motor state for half hour intervals. The participants answered the Hauser diary on whether they had been ON without troublesome dyskinesia. A diary day started with the interval 24:00-0:30 through 23:30-24:00 on each chronological day for 3 consecutive days. On the days recording the home diary, participants made an entry every 30 minutes during their normal waking time and upon awakening from time asleep.

The daily ON hours was calculated as the average of the 3 consecutive daily ON hours from the Hauser diary at each visit.

Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10.

Outcome measures

Measure	Placebo n=21 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=7 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=41 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Change From Baseline in Daily ON Time Without Troublesome Dyskinesia Change at Week 3	0.61 Hours Standard Error 0.577	1.74 Hours Standard Error 1.173	-0.49 Hours Standard Error 1.047	1.93 Hours Standard Error 1.128	0.77 Hours Standard Error 0.443
Change From Baseline in Daily ON Time Without Troublesome Dyskinesia Change at Week 5	0.02 Hours Standard Error 0.548	2.39 Hours Standard Error 1.150	1.31 Hours Standard Error 1.058	1.12 Hours Standard Error 1.029	1.31 Hours Standard Error 0.436
Change From Baseline in Daily ON Time Without Troublesome Dyskinesia Change at Week 10	0.61 Hours Standard Error 0.618	0.92 Hours Standard Error 1.413	0.45 Hours Standard Error 1.598	2.64 Hours Standard Error 1.194	1.65 Hours Standard Error 0.508
Change From Baseline in Daily ON Time Without Troublesome Dyskinesia Change at Week 15	-0.81 Hours Standard Error 1.099	0.37 Hours Standard Error 2.999	-4.48 Hours Standard Error 3.192	0.94 Hours Standard Error 1.781	1.50 Hours Standard Error 0.825

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 5, 10 and 15; Baseline was defined as the Day -1 (study derived day and equalled to nominal visit Day 0) measurement

Population: Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary).

MDS-UPDRS Part III assessed the motor signs of Parkinson's disease and was administered by the investigator. It was comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question was anchored with 5 responses that were linked to commonly accepted clinical terms: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. If more than 7 of the Part III items were missing, the score for that time point was missing, otherwise MDS-UPDRS Part III score was imputed as sum of the non-missing items*(total number of items)/ (number of items non-missing). The MDS-UPDRS Part III total score range is 0-132. Higher score indicated more severe motor signs of Parkinson's disease.

Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10.

Outcome measures

Measure	Placebo n=21 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=7 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=41 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Change at Week 1	-3.90 units on a scale Standard Error 2.054	-4.44 units on a scale Standard Error 3.965	-4.61 units on a scale Standard Error 3.593	-1.90 units on a scale Standard Error 3.594	-3.22 units on a scale Standard Error 1.524
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Change at Week 2	-0.95 units on a scale Standard Error 2.078	-15.78 units on a scale Standard Error 6.252	—	0.56 units on a scale Standard Error 6.129	-3.70 units on a scale Standard Error 1.584
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Change at Week 3	-3.80 units on a scale Standard Error 2.848	-12.39 units on a scale Standard Error 8.240	—	—	-3.06 units on a scale Standard Error 2.069
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Change at Week 4	-6.28 units on a scale Standard Error 2.182	-0.84 units on a scale Standard Error 3.940	-2.48 units on a scale Standard Error 3.572	-2.91 units on a scale Standard Error 3.575	-6.05 units on a scale Standard Error 1.574
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Change at Week 5	-5.12 units on a scale Standard Error 2.386	-6.14 units on a scale Standard Error 4.414	3.10 units on a scale Standard Error 4.347	-1.22 units on a scale Standard Error 3.935	-4.86 units on a scale Standard Error 1.765
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Change at Week 10	-5.09 units on a scale Standard Error 1.967	-2.21 units on a scale Standard Error 3.902	5.77 units on a scale Standard Error 5.365	-2.36 units on a scale Standard Error 3.607	-9.32 units on a scale Standard Error 1.526
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Change at Week 15	-0.18 units on a scale Standard Error 3.170	7.72 units on a scale Standard Error 8.660	2.09 units on a scale Standard Error 9.495	-5.44 units on a scale Standard Error 5.364	-1.84 units on a scale Standard Error 2.519

SECONDARY outcome

Timeframe: Weeks 5, 10 and 15; Baseline was defined as the Day -1 (study derived day and equalled to nominal visit Day 0) measurement

Population: Full Analysis Set included all participants randomized who completed at least 1 postdose efficacy measurement(Hauser home diary).

Each question of Part I,II or IV with 5 responses was linked to the same clinical terms as Part III.The score was missing if more than 7 items were missing for a time point; otherwise Part I,II or IV score was imputed as sum of non-missing items*(total number of items)/(number of items non-missing).•PartI (Non-Motor Aspects of Experiences of Daily Living) assessed non-motor experiences of daily living using 13questions(Range:0-52).•PartII(Motor Aspects of Experiences of Daily Living) assessed motor experiences of daily living using 13questions(Range:0-52).•PartIV(Motor Complications) assessed motor complications,dyskinesias, and motor fluctuations using historical and objective information with 6questions(Range:0-24).•MDS-UPDRS Total Score:the sum of Parts I,II,III,and IV(Range:0-260).Higher score indicated more severe motor signs of Parkinson's disease.Week15's results were interpreted cautiously given almost half participants were not available for the analysis as compared to Week10

Outcome measures

Measure	Placebo n=21 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=7 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=9 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=41 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 5 (Part I Score)	-0.75 units on a scale Standard Deviation 5.508	-0.83 units on a scale Standard Deviation 1.941	0.67 units on a scale Standard Deviation 4.885	2.00 units on a scale Standard Deviation 4.408	1.12 units on a scale Standard Deviation 4.879
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 10 (Part I Score)	-0.69 units on a scale Standard Deviation 4.557	-0.80 units on a scale Standard Deviation 2.168	-1.00 units on a scale Standard Deviation 2.828	0.00 units on a scale Standard Deviation 2.449	0.17 units on a scale Standard Deviation 4.086
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 15 (Part I Score)	-2.86 units on a scale Standard Deviation 6.176	2.00 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	6.00 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	-1.00 units on a scale Standard Deviation 1.732	1.00 units on a scale Standard Deviation 5.745
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 5 (Part II Score)	0.06 units on a scale Standard Deviation 5.836	-1.83 units on a scale Standard Deviation 2.639	3.00 units on a scale Standard Deviation 4.940	-0.03 units on a scale Standard Deviation 3.083	-0.24 units on a scale Standard Deviation 4.068
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 10 (Part II Score)	-0.35 units on a scale Standard Deviation 5.267	-1.00 units on a scale Standard Deviation 1.225	5.00 units on a scale Standard Deviation 1.414	0.13 units on a scale Standard Deviation 2.428	-0.43 units on a scale Standard Deviation 4.240
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 15 (Part II Score)	-1.38 units on a scale Standard Deviation 4.779	2.00 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	8.00 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	-2.42 units on a scale Standard Deviation 5.270	1.47 units on a scale Standard Deviation 5.986
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 5 (Part IV Score)	-1.50 units on a scale Standard Deviation 2.895	-0.83 units on a scale Standard Deviation 2.401	-0.50 units on a scale Standard Deviation 4.848	0.25 units on a scale Standard Deviation 2.053	-0.65 units on a scale Standard Deviation 2.806
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 10 (Part IV Score)	-2.00 units on a scale Standard Deviation 2.318	0.80 units on a scale Standard Deviation 1.304	-3.00 units on a scale Standard Deviation 5.657	0.00 units on a scale Standard Deviation 1.789	-1.13 units on a scale Standard Deviation 3.530
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 15 (Part IV Score)	-2.75 units on a scale Standard Deviation 2.493	-2.00 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	-7.00 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	-1.33 units on a scale Standard Deviation 2.082	-1.27 units on a scale Standard Deviation 2.404
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 5 (Total Score)	-8.88 units on a scale Standard Deviation 12.832	-10.00 units on a scale Standard Deviation 7.616	5.33 units on a scale Standard Deviation 16.860	2.34 units on a scale Standard Deviation 12.010	-4.21 units on a scale Standard Deviation 18.216
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 10 (Total Score)	-8.75 units on a scale Standard Deviation 10.951	-3.60 units on a scale Standard Deviation 8.649	6.50 units on a scale Standard Deviation 7.778	0.13 units on a scale Standard Deviation 10.569	-11.40 units on a scale Standard Deviation 18.448
Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score Change at Week 15 (Total Score)	-7.86 units on a scale Standard Deviation 12.456	0.00 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	13.00 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	-9.08 units on a scale Standard Deviation 13.135	0.73 units on a scale Standard Deviation 17.260

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 17

Population: Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo.

The safety laboratory tests including Hematology, Clinical Chemistry and Urinalysis were performed.

Determination if there were any laboratory data abnormalities of potential clinical concern was based on Pfizer Data Standards.

Incidence of laboratory test abnormalities (without regard to baseline abnormality) was summarized within each treatment group.

Outcome measures

Measure	Placebo n=23 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=12 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality	19 Participants	4 Participants	9 Participants	7 Participants	25 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 17

Population: Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified categories.

Vital Signs including blood pressure and pulse rate were measured. Vital signs were collected first while the participant was in the supine position and then in the standing position.

Outcome measures

Measure	Placebo n=23 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization >140 bpm (Standing Pulse Rate)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization <90 mmHg (Supine Systolic Blood Pressure [SBP])	1 Participants	1 Participants	2 Participants	0 Participants	3 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization Max-Increase from Baseline >= 30 mmHg (Supine SBP)	4 Participants	1 Participants	2 Participants	1 Participants	3 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization Max-Decrease from Baseline >= 30 mmHg (Supine SBP)	4 Participants	1 Participants	2 Participants	2 Participants	11 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization <90 mmHg (Standing SBP)	4 Participants	1 Participants	3 Participants	2 Participants	7 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization Max-Increase from Baseline >=30mmHg (Standing SBP)	4 Participants	0 Participants	3 Participants	1 Participants	3 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization Max-Decrease from Baseline >=30mmHg (Standing SBP)	3 Participants	0 Participants	3 Participants	2 Participants	12 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization <50 mmHg (Supine Diastolic Blood Pressure [DBP])	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization Max-Increase from Baseline >=20 mmHg (Supine DBP)	1 Participants	0 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization Max-Decrease from Baseline >=20 mmHg (Supine DBP)	1 Participants	0 Participants	2 Participants	1 Participants	13 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization <50 mmHg (Standing DBP)	2 Participants	0 Participants	1 Participants	2 Participants	1 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization Max-Increase from Baseline >=20mmHg (Standing DBP)	3 Participants	0 Participants	2 Participants	0 Participants	1 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization Max-Decrease from Baseline >=20mmHg (Standing DBP)	5 Participants	2 Participants	3 Participants	2 Participants	17 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization <40 beats per minute (bpm) (Supine Pulse Rate)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization >120 bpm (Supine Pulse Rate)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization <40 bpm (Standing Pulse Rate)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 17

Population: Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified categories.

The average of the triplicate readings of ECG data was collected at each assessment time.

Number of participants with ECG results meeting the criteria for categorical summarization for time from the beginning of the P wave until the beginning of the QRS complex (PR Interval), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS Duration), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT Interval) and corrected QT (Fridericia correction) (QTcF Interval) were presented.

Outcome measures

Measure	Placebo n=23 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=12 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization Max-Increase From Baseline >=60 (QTcF Interval)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization >=300 msec (PR Interval)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization Max-Increase From Baseline(%)>=25/50%(PR Interval)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization >=140 msec (QRS Duration)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization Max-Increase From Baseline(%)>=50% (QRS Duration)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization >=500 msec (QT Interval)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization 450 - <480 msec (QTcF Interval)	2 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization 480 - <500 msec (QTcF Interval)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization >=500 msec (QTcF Interval)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization Max-Increase From Baseline 30-<60 (QTcF Interval)	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Days 0 (Baseline), 7, 14, 21, 28, 35, 70, 77, 84, 91, 105 and 119

Population: Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified time points.

The Columbia Suicide Severity Rating Scale (C-SSRS) was an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS responses were mapped to the C-CASA. There were 3 key endpoints for suicidality data analysis and evaluation:

• Suicidal Behavior: A participant was said to have suicidal behavior if the participant had experienced completed suicide / suicide attempt / reparatory acts toward imminent suicidal behavior.
• Suicidal Ideation: Any observed suicidal ideation mapped to a single C-CASA category.
• Suicidal Behavior or Ideation (participants with new onset suicidality): A participant was considered to have a new onset of suicidality if the participant reported no ideation and no behavior at the baseline assessment and reported any behavior or ideation post-baseline. Data observed at screening was not considered in the definition of worsening.

Outcome measures

Measure	Placebo n=23 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Baseline	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 7	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 14	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 21	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 28	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 35	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 70	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 77	0 Participants	—	—	—	0 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 84	0 Participants	—	—	—	0 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 91	0 Participants	—	—	—	0 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 105	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits Day 119	0 Participants	0 Participants	—	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0) and Weeks 5, 10 and 15

Population: Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified time points.

The QUIP-RS was a brief, patient reported outcome measure designed to assess the severity of symptoms of Impulsive-Compulsive Disorders (ICDs) and related behaviors reported to occur in Parkinson's disease.

The QUIP-RS assessed 7 disorders (Gambling, Sex, Buying, Eating, Hobbyism-punding [performing tasks and repeating activities] and Taking medications). If more than 5 items were missing, the total QUIP-RS score was set as missing; otherwise, the total QUIP-RS score was imputed as follows: sum of the non-missing item scores * (total number of items) / (number of items non-missing). The higher score indicated a greater level of the ICD.

The total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112.

Outcome measures

Measure	Placebo n=23 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Change From Baseline in Total Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Baseline	17.1 units on a scale Standard Deviation 16.98	9.0 units on a scale Standard Deviation 12.56	9.0 units on a scale Standard Deviation 14.39	12.5 units on a scale Standard Deviation 11.69	6.8 units on a scale Standard Deviation 11.40
Change From Baseline in Total Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Change at Week 5	-5.6 units on a scale Standard Deviation 11.37	2.3 units on a scale Standard Deviation 10.05	4.7 units on a scale Standard Deviation 9.58	-5.4 units on a scale Standard Deviation 12.28	0.5 units on a scale Standard Deviation 11.13
Change From Baseline in Total Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Change at Week 10	-3.3 units on a scale Standard Deviation 12.16	-1.8 units on a scale Standard Deviation 7.98	-6.5 units on a scale Standard Deviation 9.63	-5.8 units on a scale Standard Deviation 13.50	1.0 units on a scale Standard Deviation 10.62
Change From Baseline in Total Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Change at Week 15	-11.5 units on a scale Standard Deviation 16.29	3.0 units on a scale Standard Deviation 10.30	-3.3 units on a scale Standard Deviation 5.77	-17.0 units on a scale Standard Deviation 11.34	0.4 units on a scale Standard Deviation 5.91

SECONDARY outcome

Timeframe: Days 105 and 119

Population: Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified time points.

The PWC-20 is a physician completed, 20 item reliable and sensitive instrument for the assessment of discontinuation symptoms. The PWC-20 was collected after the completion of study treatment and also at the first visit of follow-up.

The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60. If more than 5 items were missing, the total PWC-20 score was missing; otherwise, the total PWC-20 score was imputed as follows: sum of the non-missing items * (total number of items) / (number of items non-missing). The higher score indicated more frequent/severe symptoms.

Outcome measures

Measure	Placebo n=23 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Total Physician Withdrawal Checklist (PWC-20) on Days 105 and 119, and Change From Day 105 to Day 119 Day 105 Early Termination (ET)	3.5 units on a scale Standard Deviation 3.73	5.6 units on a scale Standard Deviation 5.68	5.8 units on a scale Standard Deviation 6.65	8.2 units on a scale Standard Deviation 8.78	7.1 units on a scale Standard Deviation 6.06
Total Physician Withdrawal Checklist (PWC-20) on Days 105 and 119, and Change From Day 105 to Day 119 Day 119 Follow-up (FU)	3.3 units on a scale Standard Deviation 3.08	6.0 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	—	7.7 units on a scale Standard Deviation 4.16	5.8 units on a scale Standard Deviation 5.45
Total Physician Withdrawal Checklist (PWC-20) on Days 105 and 119, and Change From Day 105 to Day 119 Change From Day 105 ET to Day 119 FU	-0.6 units on a scale Standard Deviation 3.08	-11.0 units on a scale Standard Deviation NA Only 1 participant evaluable in this treatment group.	—	-1.7 units on a scale Standard Deviation 4.73	-0.4 units on a scale Standard Deviation 4.79

SECONDARY outcome

Timeframe: Day 1 to follow-up (Week 19 visit)

Population: Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo.

An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not need necessarily to have a causal relationship with the treatment or usage.

An SAE was any untoward medical occurrence at any dose that:

• Resulted in death;
• Was life threatening (immediate risk of death);
• Required inpatient hospitalization or prolongation of existing hospitalization;
• Resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions);
• Resulted in congenital anomaly/birth defect.

Outcome measures

Measure	Placebo n=23 Participants The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 Participants The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs and Deaths AEs	20 Participants	7 Participants	11 Participants	10 Participants	37 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs and Deaths SAEs	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs and Deaths Discontinuation due to AEs	3 Participants	1 Participants	3 Participants	2 Participants	9 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs and Deaths Death	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 15 other events

Deaths: 1 deaths

PF-06649751 1 mg QD

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

PF-06649751 3 mg QD

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

PF-06649751 7 mg QD

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

PF-06649751 15 mg QD

Serious events: 2 serious events

Other events: 31 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo n=23 participants at risk The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=13 participants at risk The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 participants at risk The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 participants at risk The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 participants at risk The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Nephrolithiasis	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Ureterolithiasis	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Abdominal pain	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Immune system disorders Allergic oedema	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Other adverse events

Measure	Placebo n=23 participants at risk The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 1 mg QD n=13 participants at risk The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 3 mg QD n=15 participants at risk The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 7 mg QD n=13 participants at risk The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.	PF-06649751 15 mg QD n=44 participants at risk The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety.
Cardiac disorders Ventricular extrasystoles	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Abdominal pain	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Constipation	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Diarrhoea	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Dysphagia	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Flatulence	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.8% 3/44 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Nausea	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 2/13 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	13.3% 2/15 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	25.0% 11/44 • Number of events 14 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Vomiting	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	4.5% 2/44 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Asthenia	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Fatigue	13.0% 3/23 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	13.3% 2/15 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 2/13 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Malaise	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Pyrexia	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Asymptomatic bacteriuria	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Chronic sinusitis	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Nasopharyngitis	13.0% 3/23 • Number of events 4 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Tooth abscess	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Bone contusion	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Contusion	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 2/13 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Fall	8.7% 2/23 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 2/13 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 2/13 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	4.5% 2/44 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Joint injury	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Laceration	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood pressure decreased	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Urine output decreased	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Decreased appetite	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.8% 3/44 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Pain in extremity	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Posture abnormal	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Balance disorder	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Dizziness	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 2/13 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	9.1% 4/44 • Number of events 4 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Dyskinesia	8.7% 2/23 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	23.1% 3/13 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.9% 7/44 • Number of events 7 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Dystonia	8.7% 2/23 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Headache	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	15.4% 2/13 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	23.1% 3/13 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	25.0% 11/44 • Number of events 14 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Memory impairment	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Myoclonus	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Neuropathy peripheral	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Parkinson's disease	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Somnolence	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Abnormal dreams	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.8% 3/44 • Number of events 4 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Aggression	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Anxiety	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.8% 3/44 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Delusion	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Depersonalisation/derealisation disorder	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Depression	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Dysphemia	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Hallucination	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Hypersexuality	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Insomnia	13.0% 3/23 • Number of events 3 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	4.5% 2/44 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Irritability	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	9.1% 4/44 • Number of events 4 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Rapid eye movement sleep behaviour disorder	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Sleep disorder	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Nephrolithiasis	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Flushing	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Hot flush	4.3% 1/23 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/15 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	7.7% 1/13 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	2.3% 1/44 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Hypertension	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Hypotension	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	13.3% 2/15 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/44 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Orthostatic hypotension	0.00% 0/23 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	6.7% 1/15 • Number of events 1 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	0.00% 0/13 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.	4.5% 2/44 • Number of events 2 • Day 1 to follow-up (Week 19 visit) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Additional Information

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Results disclosure agreements

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

Restriction type: OTHER