Trial Outcomes & Findings for Dyskinesia in Parkinson's Disease (Study P04501) (NCT NCT00406029)

NCT ID: NCT00406029

Last Updated: 2018-11-09

Results Overview

"Off" time refers to periods of inadequate control of Parkinson disease symptoms (worsening or presence of symptoms). For baseline and the 12 weeks treatment period, hours spent in the "off" state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. Change from baseline in least squares (LS) means and pooled standard deviation (SD) were obtained from an analysis of covariance (ANCOVA) model with effect for treatment and baseline covariate. A negative change from baseline signifies less time spent in the "off" state.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 253 participants
• Primary outcome timeframe: Baseline (Week -1) and up to 12 weeks
• Results posted on: 2018-11-09

Participant Flow

Participant milestones

Measure	Preladenant 1 mg BID Participants received preladenant 1 mg twice daily (BID) during the 12-week treatment period.	Preladenant 2 mg BID Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID Participants received preladenant matching placebo BID during the 12-week treatment period.
Overall Study STARTED	49	49	49	57	49
Overall Study Treated	49	49	47	54	47
Overall Study COMPLETED	33	41	39	40	41
Overall Study NOT COMPLETED	16	8	10	17	8

Reasons for withdrawal

Measure	Preladenant 1 mg BID Participants received preladenant 1 mg twice daily (BID) during the 12-week treatment period.	Preladenant 2 mg BID Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID Participants received preladenant matching placebo BID during the 12-week treatment period.
Overall Study Adverse Event	12	2	5	10	7
Overall Study Withdrawal by Subject	3	4	2	2	0
Overall Study Protocol Violation	1	2	0	2	0
Overall Study Did Not Meet Eligibility Criteria	0	0	1	0	0
Overall Study Randomized in Error	0	0	2	3	1

Baseline Characteristics

Dyskinesia in Parkinson's Disease (Study P04501)

Baseline characteristics by cohort

Measure	Preladenant 1 mg BID n=49 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=49 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=47 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=54 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=47 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.	Total n=246 Participants Total of all reporting groups
Age, Customized Between 18 and 65 years	30 Participants n=5 Participants	25 Participants n=7 Participants	24 Participants n=5 Participants	32 Participants n=4 Participants	27 Participants n=21 Participants	138 Participants n=8 Participants
Age, Customized >=65 years	19 Participants n=5 Participants	24 Participants n=7 Participants	23 Participants n=5 Participants	22 Participants n=4 Participants	20 Participants n=21 Participants	108 Participants n=8 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants	22 Participants n=4 Participants	16 Participants n=21 Participants	87 Participants n=8 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	36 Participants n=7 Participants	30 Participants n=5 Participants	32 Participants n=4 Participants	31 Participants n=21 Participants	159 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline (Week -1) and up to 12 weeks

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the "off" state) was used for analysis.

"Off" time refers to periods of inadequate control of Parkinson disease symptoms (worsening or presence of symptoms). For baseline and the 12 weeks treatment period, hours spent in the "off" state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. Change from baseline in least squares (LS) means and pooled standard deviation (SD) were obtained from an analysis of covariance (ANCOVA) model with effect for treatment and baseline covariate. A negative change from baseline signifies less time spent in the "off" state.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline to Endpoint of 12 Weeks in the 3-day Average of Awake Time Per Day Spent in the "Off" State	-0.4 hours/day Standard Deviation 2.48	-1.3 hours/day Standard Deviation 2.48	-1.6 hours/day Standard Deviation 2.48	-1.7 hours/day Standard Deviation 2.48	-0.5 hours/day Standard Deviation 2.48

SECONDARY outcome

Timeframe: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the "off" state) for the assessment week was used for analysis.

"Off" time refers to periods of inadequate control of Parkinson disease symptoms (worsening or presence of symptoms). Hours spent in the "off" state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with treatment effect and baseline covariate. A negative change from baseline signifies less time spent in the "off" state.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Awake Time Per Day Spent in the "Off" State at Each Visit Week 12 (n=29,39,37,38,37)	-1.1 hours/day Standard Deviation 2.42	-1.4 hours/day Standard Deviation 2.42	-1.6 hours/day Standard Deviation 2.42	-1.9 hours/day Standard Deviation 2.42	-0.4 hours/day Standard Deviation 2.42
Change From Baseline in Awake Time Per Day Spent in the "Off" State at Each Visit Week 2 (n=46,47,43,49,45)	-0.3 hours/day Standard Deviation 2.11	-0.6 hours/day Standard Deviation 2.11	-1.0 hours/day Standard Deviation 2.11	-1.2 hours/day Standard Deviation 2.11	-0.2 hours/day Standard Deviation 2.11
Change From Baseline in Awake Time Per Day Spent in the "Off" State at Each Visit Week 4 (n=45,47,45,44,42)	-0.5 hours/day Standard Deviation 2.36	-1.1 hours/day Standard Deviation 2.36	-1.1 hours/day Standard Deviation 2.36	-0.9 hours/day Standard Deviation 2.36	-0.5 hours/day Standard Deviation 2.36
Change From Baseline in Awake Time Per Day Spent in the "Off" State at Each Visit Week 6 (n=39,46,42,41,42)	-0.3 hours/day Standard Deviation 2.58	-1.4 hours/day Standard Deviation 2.58	-1.3 hours/day Standard Deviation 2.58	-1.0 hours/day Standard Deviation 2.58	-0.8 hours/day Standard Deviation 2.58
Change From Baseline in Awake Time Per Day Spent in the "Off" State at Each Visit Week 8 (n=36,45,40,34,41)	-0.8 hours/day Standard Deviation 2.34	-1.2 hours/day Standard Deviation 2.34	-1.1 hours/day Standard Deviation 2.34	-1.7 hours/day Standard Deviation 2.34	-0.5 hours/day Standard Deviation 2.34
Change From Baseline in Awake Time Per Day Spent in the "Off" State at Each Visit Week 10 (n=35,42,40,36,41)	-0.3 hours/day Standard Deviation 2.31	-1.3 hours/day Standard Deviation 2.31	-1.7 hours/day Standard Deviation 2.31	-1.9 hours/day Standard Deviation 2.31	-0.4 hours/day Standard Deviation 2.31

SECONDARY outcome

Timeframe: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the "on" state) for the assessment week was used for analysis.

"On" time refers to periods of adequate control of Parkinson disease symptoms (symptoms better or absent). Hours spent in the "on" state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. A positive (+) change from baseline signifies more time spent in the "on" state.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Awake Time Per Day Spent in the "on" State Endpoint (n=47,48,45,49,45)	0.4 hours/day Standard Deviation 2.59	0.7 hours/day Standard Deviation 2.59	1.4 hours/day Standard Deviation 2.59	1.3 hours/day Standard Deviation 2.59	0.2 hours/day Standard Deviation 2.59
Change From Baseline in Awake Time Per Day Spent in the "on" State Week 2 (n=46,47,43,49,45)	0.4 hours/day Standard Deviation 2.18	0.4 hours/day Standard Deviation 2.18	0.9 hours/day Standard Deviation 2.18	1.0 hours/day Standard Deviation 2.18	0.1 hours/day Standard Deviation 2.18
Change From Baseline in Awake Time Per Day Spent in the "on" State Week 4 (n=45,47,45,44,42)	0.5 hours/day Standard Deviation 2.45	0.6 hours/day Standard Deviation 2.45	0.8 hours/day Standard Deviation 2.45	0.7 hours/day Standard Deviation 2.45	0.3 hours/day Standard Deviation 2.45
Change From Baseline in Awake Time Per Day Spent in the "on" State Week 6 (n=39,46,42,41,42)	0.3 hours/day Standard Deviation 2.86	1.0 hours/day Standard Deviation 2.86	1.0 hours/day Standard Deviation 2.86	1.0 hours/day Standard Deviation 2.86	0.6 hours/day Standard Deviation 2.86
Change From Baseline in Awake Time Per Day Spent in the "on" State Week 8 (n=36,45,40,34,41)	0.8 hours/day Standard Deviation 2.59	1.0 hours/day Standard Deviation 2.59	1.1 hours/day Standard Deviation 2.59	1.1 hours/day Standard Deviation 2.59	0.2 hours/day Standard Deviation 2.59
Change From Baseline in Awake Time Per Day Spent in the "on" State Week 10 (n=35,42,40,34,41)	0.2 hours/day Standard Deviation 2.40	0.9 hours/day Standard Deviation 2.40	1.5 hours/day Standard Deviation 2.40	1.4 hours/day Standard Deviation 2.40	0.1 hours/day Standard Deviation 2.40
Change From Baseline in Awake Time Per Day Spent in the "on" State Week 12 (n=29,39,37,38,37)	1.0 hours/day Standard Deviation 2.64	0.8 hours/day Standard Deviation 2.64	1.8 hours/day Standard Deviation 2.64	1.4 hours/day Standard Deviation 2.64	0.1 hours/day Standard Deviation 2.64

SECONDARY outcome

Timeframe: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the "on" state with no dyskinesias) for the assessment week was used for analysis.

"On" time refers to periods of adequate control of Parkinson disease symptoms (better/absent). Dyskinesias refers to maintenance therapy (e.g., L-dopa) side effects of chorea, dystonia, or in combination. Hours spent in the "on" state with no dyskinesias during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained from an ANCOVA model with effect for treatment & baseline covariate. A (+) change from baseline signifies more time spent in the "on" state (no dyskinesias).

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias) Week 2 (n=46,47,43,49,45)	0.9 hours/day Standard Deviation 2.54	0.1 hours/day Standard Deviation 2.54	0.7 hours/day Standard Deviation 2.54	0.3 hours/day Standard Deviation 2.54	0.1 hours/day Standard Deviation 2.54
Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias) Week 4 (n=45,47,45,44,42)	0.8 hours/day Standard Deviation 2.90	0.3 hours/day Standard Deviation 2.90	0.6 hours/day Standard Deviation 2.90	0.1 hours/day Standard Deviation 2.90	0.1 hours/day Standard Deviation 2.90
Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias) Week 6 (n=39,46,42,41,42)	0.8 hours/day Standard Deviation 3.31	0.4 hours/day Standard Deviation 3.31	0.9 hours/day Standard Deviation 3.31	0.2 hours/day Standard Deviation 3.31	0.3 hours/day Standard Deviation 3.31
Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias) Week 8 (n=36,45,40,34,41)	1.1 hours/day Standard Deviation 3.28	0.0 hours/day Standard Deviation 3.28	1.0 hours/day Standard Deviation 3.28	0.1 hours/day Standard Deviation 3.28	0.5 hours/day Standard Deviation 3.28
Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias) Week 10 (n=35,42,40,36,41)	0.7 hours/day Standard Deviation 3.40	0.1 hours/day Standard Deviation 3.40	1.4 hours/day Standard Deviation 3.40	0.6 hours/day Standard Deviation 3.40	0.6 hours/day Standard Deviation 3.40
Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias) Week 12 (n=29,39,37,38,37)	1.2 hours/day Standard Deviation 3.70	0.2 hours/day Standard Deviation 3.70	1.4 hours/day Standard Deviation 3.70	0.5 hours/day Standard Deviation 3.70	0.9 hours/day Standard Deviation 3.70
Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias) Endpoint (n=47,48,45,49,45)	1.0 hours/day Standard Deviation 3.58	0.2 hours/day Standard Deviation 3.58	1.2 hours/day Standard Deviation 3.58	0.7 hours/day Standard Deviation 3.58	0.9 hours/day Standard Deviation 3.58

SECONDARY outcome

Timeframe: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the "on" state with troublesome dyskinesias) for the assessment week was used for analysis.

"On" time refers to periods of adequate control of Parkinson disease symptoms (better/absent). Troublesome dyskinesias refers to maintenance therapy side effects of chorea, dystonia, or in combination that impair function. Hours spent in the "on" state with troublesome dyskinesias during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained using ANCOVA with treatment effect & baseline covariate. A (+) change from baseline signifies more time spent in the "on" state (troublesome dyskinesias).

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias) Week 2 (n=46,47,43,49,45)	-0.2 hours/day Standard Deviation 1.21	-0.2 hours/day Standard Deviation 1.21	0.0 hours/day Standard Deviation 1.21	0.2 hours/day Standard Deviation 1.21	0.3 hours/day Standard Deviation 1.21
Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias) Week 4 (n=45,47,45,44,42)	-0.1 hours/day Standard Deviation 1.39	0.0 hours/day Standard Deviation 1.39	0.0 hours/day Standard Deviation 1.39	0.2 hours/day Standard Deviation 1.39	0.2 hours/day Standard Deviation 1.39
Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias) Week 6 (n=39,46,42,41,42)	-0.2 hours/day Standard Deviation 1.81	0.1 hours/day Standard Deviation 1.81	-0.3 hours/day Standard Deviation 1.81	0.2 hours/day Standard Deviation 1.81	0.3 hours/day Standard Deviation 1.81
Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias) Week 8 (n=36,45,40,34,41)	-0.2 hours/day Standard Deviation 1.65	0.2 hours/day Standard Deviation 1.65	0.0 hours/day Standard Deviation 1.65	0.1 hours/day Standard Deviation 1.65	0.1 hours/day Standard Deviation 1.65
Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias) Week 10 (n=35,42,40,36,41)	-0.3 hours/day Standard Deviation 1.61	0.1 hours/day Standard Deviation 1.61	-0.1 hours/day Standard Deviation 1.61	0.1 hours/day Standard Deviation 1.61	0.1 hours/day Standard Deviation 1.61
Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias) Week 12 (n=29,39,37,38,37)	0.0 hours/day Standard Deviation 1.84	0.2 hours/day Standard Deviation 1.84	0.2 hours/day Standard Deviation 1.84	0.4 hours/day Standard Deviation 1.84	0.1 hours/day Standard Deviation 1.84
Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias) Endpoint (n=47,48,45,49,45)	-0.1 hours/day Standard Deviation 1.79	0.1 hours/day Standard Deviation 1.79	0.1 hours/day Standard Deviation 1.79	0.4 hours/day Standard Deviation 1.79	0.1 hours/day Standard Deviation 1.79

SECONDARY outcome

Timeframe: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the "on" state without troublesome dyskinesias) for the assessment week was used for analysis.

"On" time refers to periods of adequate control of Parkinson disease symptoms (better/absent). Troublesome dyskinesias refers to maint. therapy side effects of chorea, dystonia, or in combination that impair function. Hours spent in the "on" state without troubles. dyskinesias during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained using ANCOVA with treatment effect & baseline covariate. A (+) change from baseline signifies more time spent in the "on" state (without troubles. dyskinesias).

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias) Week 2 (n=46,47,43,49,45)	-0.3 hours/day Standard Deviation 1.95	0.5 hours/day Standard Deviation 1.95	0.2 hours/day Standard Deviation 1.95	0.5 hours/day Standard Deviation 1.95	-0.3 hours/day Standard Deviation 1.95
Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias) Week 4 (n=45,47,45,44,42)	-0.2 hours/day Standard Deviation 2.31	0.2 hours/day Standard Deviation 2.31	0.3 hours/day Standard Deviation 2.31	0.4 hours/day Standard Deviation 2.31	0.0 hours/day Standard Deviation 2.31
Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias) Week 6 (n=39,46,42,41,42)	-0.2 hours/day Standard Deviation 2.64	0.5 hours/day Standard Deviation 2.64	0.5 hours/day Standard Deviation 2.64	0.5 hours/day Standard Deviation 2.64	-0.1 hours/day Standard Deviation 2.64
Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias) Week 8 (n=36,45,40,34,41)	-0.1 hours/day Standard Deviation 2.73	0.8 hours/day Standard Deviation 2.73	0.3 hours/day Standard Deviation 2.73	0.8 hours/day Standard Deviation 2.73	-0.5 hours/day Standard Deviation 2.73
Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias) Week 10 (n=35,42,40,36,41)	-0.2 hours/day Standard Deviation 2.64	0.7 hours/day Standard Deviation 2.64	0.2 hours/day Standard Deviation 2.64	0.7 hours/day Standard Deviation 2.64	-0.5 hours/day Standard Deviation 2.64
Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias) Week 12 (n=29,39,37,38,37)	-0.2 hours/day Standard Deviation 2.73	0.4 hours/day Standard Deviation 2.73	0.2 hours/day Standard Deviation 2.73	0.5 hours/day Standard Deviation 2.73	-1.0 hours/day Standard Deviation 2.73
Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias) Endpoint (n=47,48,45,49,45	-0.4 hours/day Standard Deviation 2.59	0.4 hours/day Standard Deviation 2.59	0.2 hours/day Standard Deviation 2.59	0.2 hours/day Standard Deviation 2.59	-0.8 hours/day Standard Deviation 2.59

SECONDARY outcome

Timeframe: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (awake time per day in the "on" state with troublesome and not troblesome dyskinesias) for the assessment week was used for analysis.

Dyskinesias refers to maintenance therapy side effects of chorea, dystonia, or in combination (that occur in the ON time). Hours spent with dyskinesias (troublesome and not troublesome) were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained using ANCOVA with treatment effect & baseline covariate. A negative change from baseline signifies less time spent with dyskinesia.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Absolute Duration of Dyskinesias Week 2 (n=46,47,43,49,45)	-0.5 hours/day Standard Deviation 2.26	0.3 hours/day Standard Deviation 2.26	0.2 hours/day Standard Deviation 2.26	0.7 hours/day Standard Deviation 2.26	0.0 hours/day Standard Deviation 2.26
Change From Baseline in Absolute Duration of Dyskinesias Week 4 (n=45,47,45,44,42)	-0.4 hours/day Standard Deviation 2.81	0.2 hours/day Standard Deviation 2.81	0.3 hours/day Standard Deviation 2.81	0.6 hours/day Standard Deviation 2.81	0.2 hours/day Standard Deviation 2.81
Change From Baseline in Absolute Duration of Dyskinesias Week 6 (n=39,46,42,41,42)	-0.5 hours/day Standard Deviation 3.25	0.6 hours/day Standard Deviation 3.25	0.2 hours/day Standard Deviation 3.25	0.7 hours/day Standard Deviation 3.25	0.2 hours/day Standard Deviation 3.25
Change From Baseline in Absolute Duration of Dyskinesias Week 8 (n=36,45,40,34,41)	-0.3 hours/day Standard Deviation 3.25	1.0 hours/day Standard Deviation 3.25	0.2 hours/day Standard Deviation 3.25	0.9 hours/day Standard Deviation 3.25	-0.3 hours/day Standard Deviation 3.25
Change From Baseline in Absolute Duration of Dyskinesias Week 10 (n=35,42,40,36,41)	-0.5 hours/day Standard Deviation 3.11	0.8 hours/day Standard Deviation 3.11	0.1 hours/day Standard Deviation 3.11	0.8 hours/day Standard Deviation 3.11	-0.4 hours/day Standard Deviation 3.11
Change From Baseline in Absolute Duration of Dyskinesias Week 12 (n=29,39,37,38,37)	-0.2 hours/day Standard Deviation 3.27	0.6 hours/day Standard Deviation 3.27	0.4 hours/day Standard Deviation 3.27	0.9 hours/day Standard Deviation 3.27	-0.9 hours/day Standard Deviation 3.27
Change From Baseline in Absolute Duration of Dyskinesias Endpoint (n=47,48,45,49,45	-0.6 hours/day Standard Deviation 3.18	0.5 hours/day Standard Deviation 3.18	0.2 hours/day Standard Deviation 3.18	0.6 hours/day Standard Deviation 3.18	-0.7 hours/day Standard Deviation 3.18

SECONDARY outcome

Timeframe: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (total sleep time) for the assessment week was used for analysis.

Hours spent in the sleep state were recorded using a daily diary at least 3 full days before scheduled visit. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. For treatment period visits, the 24-hour average was derived for the final 3 consecutive days with data available for the particular visit. Change from baseline in LS means & pooled SD were obtained using ANCOVA with treatment effect & baseline covariate. A positive change from baseline means more time asleep and a negative change means less time asleep.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Total Sleep Time Endpoint (n=47,48,45,49,45)	0.2 hours/day Standard Deviation 1.33	0.5 hours/day Standard Deviation 1.33	0.1 hours/day Standard Deviation 1.33	0.2 hours/day Standard Deviation 1.33	0.1 hours/day Standard Deviation 1.33
Change From Baseline in Total Sleep Time Week 2 (n=46,47,43,49,45)	0.0 hours/day Standard Deviation 1.14	0.2 hours/day Standard Deviation 1.14	0.1 hours/day Standard Deviation 1.14	0.1 hours/day Standard Deviation 1.14	0.0 hours/day Standard Deviation 1.14
Change From Baseline in Total Sleep Time Week 4 (n=45,47,45,44,42)	0.1 hours/day Standard Deviation 1.23	0.5 hours/day Standard Deviation 1.23	0.1 hours/day Standard Deviation 1.23	0.2 hours/day Standard Deviation 1.23	0.1 hours/day Standard Deviation 1.23
Change From Baseline in Total Sleep Time Week 6 (n=39,46,42,41,42)	0.1 hours/day Standard Deviation 1.28	0.4 hours/day Standard Deviation 1.28	-0.1 hours/day Standard Deviation 1.28	0.1 hours/day Standard Deviation 1.28	0.2 hours/day Standard Deviation 1.28
Change From Baseline in Total Sleep Time Week 8 (n=36,45,40,34,41)	0.1 hours/day Standard Deviation 1.43	0.2 hours/day Standard Deviation 1.43	0.1 hours/day Standard Deviation 1.43	0.2 hours/day Standard Deviation 1.43	0.2 hours/day Standard Deviation 1.43
Change From Baseline in Total Sleep Time Week 10 (n=35,42,40,36,41)	0.2 hours/day Standard Deviation 1.34	0.3 hours/day Standard Deviation 1.34	0.3 hours/day Standard Deviation 1.34	0.5 hours/day Standard Deviation 1.34	0.2 hours/day Standard Deviation 1.34
Change From Baseline in Total Sleep Time Week 12 (n=29,39,37,38,37)	0.2 hours/day Standard Deviation 1.24	0.5 hours/day Standard Deviation 1.24	0.0 hours/day Standard Deviation 1.24	0.3 hours/day Standard Deviation 1.24	0.2 hours/day Standard Deviation 1.24

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Week 2

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 2) (as reported by the participant). For example, someone who had >2 sleep attacks at BL who had a decrease of 1-2 by Week 2 would be reported as BL >2 to WK2 1-2. BL = baseline. WK = week.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 0 to WK2 <-2 (n=36,42,39,43,41)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 0 to WK2 -1,-2 (n=36,42,39,43,41)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 0 to WK2 0 (n=36,42,39,43,41)	31 Participants	39 Participants	36 Participants	41 Participants	37 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 0 to WK2 1,2 (n=36,42,39,43,41)	3 Participants	1 Participants	1 Participants	1 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 0 to WK2 >-2 (n=36,42,39,43,41)	2 Participants	2 Participants	2 Participants	1 Participants	3 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 1,2 to WK2 <-2 (n=4,2,2,2,1)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 1,2 to WK2 -1,-2 (n=4,2,2,2,1)	2 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 1,2 to WK2 0 (n=4,2,2,2,1)	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 1,2 to WK2 1,2 (n=4,2,2,2,1)	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL 1,2 to WK2 >-2 (n=4,2,2,2,1)	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL >2 to WK2 <-2 (n=6,2,4,0,2)	3 Participants	0 Participants	2 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL >2 to WK2 -1,-2 (n=6,2,4,0,2)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL >2 to WK2 0 (n=6,2,4,0,2)	3 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL >2 to WK2 1,2 (n=6,2,4,0,2)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 2 BL >2 to WK2 >-2 (n=6,2,4,0,2)	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Week 4

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 4) (as reported by the participant). For example, someone who had >2 sleep attacks at BL who had a decrease of 1-2 by Week 4 would be reported as BL >2 to WK4 1-2. BL = baseline. WK = week.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 0 to WK4 <-2 (n=32,43,39,43,39)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 0 to WK4 -1,-2 (n=32,43,39,43,39)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 0 to WK4 0 (n=32,43,39,43,39)	30 Participants	40 Participants	34 Participants	40 Participants	36 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 0 to WK4 1,2 (n=32,43,39,43,39)	1 Participants	3 Participants	3 Participants	2 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 0 to WK4 >-2 (n=32,43,39,43,39)	1 Participants	0 Participants	2 Participants	1 Participants	2 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 1,2 to WK4 <-2 (n=3,2,2,1,1)	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 1,2 to WK4 -1,-2 (n=3,2,2,1,1)	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 1,2 to WK4 0 (n=3,2,2,1,1)	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 1,2 to WK4 1,2 (n=3,2,2,1,1)	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL 1,2 to WK4 >-2 (n=3,2,2,1,1)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL >2 to WK4 <-2 (n=6,2,4,0,2)	5 Participants	1 Participants	2 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL >2 to WK4 -1,-2 (n=6,2,4,0,2)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL >2 to WK4 0 (n=6,2,4,0,2)	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL >2 to WK4 1,2 (n=6,2,4,0,2)	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 4 BL >2 to WK4 >-2 (n=6,2,4,0,2)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Week 6

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 6) (as reported by the participant). For example, someone who had >2 sleep attacks at BL who had a decrease of 1-2 by Week 6 would be reported as BL >2 to WK6 1-2. BL = baseline. WK = week.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 0 to WK6 <-2 (n=30,39,37,34,39)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 0 to WK6 -1,-2 (n=30,39,37,34,39)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 0 to WK6 0 (n=30,39,37,34,39)	28 Participants	38 Participants	32 Participants	34 Participants	36 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 0 to WK6 1,2 (n=30,39,37,34,39)	1 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 0 to WK6 >-2 (n=30,39,37,34,39)	1 Participants	1 Participants	4 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 1,2 to WK6 <-2 (n=4,2,2,1,1)	1 Participants	1 Participants	2 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 1,2 to WK6 -1,-2 (n=4,2,2,1,1)	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 1,2 to WK6 0 (n=4,2,2,1,1)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 1,2 to WK6 1,2 (n=4,2,2,1,1)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL 1,2 to WK6 >-2 (n=4,2,2,1,1)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL >2 to WK6 <-2 (n=6,2,4,0,2)	5 Participants	1 Participants	3 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL >2 to WK6 -1,-2 (n=6,2,4,0,2)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL >2 to WK6 0 (n=6,2,4,0,2)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL >2 to WK6 1,2 (n=6,2,4,0,2)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 6 BL >2 to WK6 >-2 (n=6,2,4,0,2)	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Week 8

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 8) (as reported by the participant). For example, someone who had >2 sleep attacks at BL who had a decrease of 1-2 by Week 8 would be reported as BL >2 to WK8 1-2. BL = baseline. WK = week.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 0 to WK8 <-2 (n=27,39,35,37,39)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 0 to WK8 -1,-2 (n=27,39,35,37,39)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 0 to WK8 0 (n=27,39,35,37,39)	24 Participants	37 Participants	33 Participants	36 Participants	36 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 0 to WK8 1,2 (n=27,39,35,37,39)	2 Participants	2 Participants	1 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 0 to WK8 >-2 (n=27,39,35,37,39)	1 Participants	0 Participants	1 Participants	1 Participants	2 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 1,2 to WK8 <-2 (n=2,2,2,1,0)	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 1,2 to WK8 -1,-2 (n=2,2,2,1,0)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 1,2 to WK8 0 (n=2,2,2,1,0)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 1,2 to WK8 1,2 (n=2,2,2,1,0)	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL 1,2 to WK8 >-2 (n=2,2,2,1,0)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL >2 to WK8 <-2 (n=5,2,4,0,2)	3 Participants	2 Participants	4 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL >2 to WK8 -1,-2 (n=5,2,4,0,2)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL >2 to WK8 0 (n=5,2,4,0,2)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL >2 to WK8 1,2 (n=5,2,4,0,2)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 8 BL >2 to WK8 >-2 (n=5,2,4,0,2)	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Week 10

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 10) (as reported by the participant). For example, someone who had >2 sleep attacks at BL who had a decrease of 1-2 by Week 10 would be reported as BL >2 to WK10 1-2. BL = baseline. WK = week.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 0 to WK10 <-2 (n=25,36,34,35,38)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 0 to WK10 -1,-2 (n=25,36,34,35,38)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 0 to WK10 0 (n=25,36,34,35,38)	21 Participants	35 Participants	31 Participants	35 Participants	36 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 0 to WK10 1,2 (n=25,36,34,35,38)	4 Participants	1 Participants	3 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 0 to WK10 >-2 (n=25,36,34,35,38)	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 1,2 to WK10 <-2 (n=3,2,2,1,1)	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 1,2 to WK10 -1,-2 (n=3,2,2,1,1)	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 1,2 to WK10 0 (n=3,2,2,1,1)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 1,2 to WK10 1,2 (n=3,2,2,1,1)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL 1,2 to WK10 >-2 (n=3,2,2,1,1)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL >2 to WK10 <-2 (n=5,2,4,0,2)	4 Participants	2 Participants	3 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL >2 to WK10 -1,-2 (n=5,2,4,0,2)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL >2 to WK10 0 (n=5,2,4,0,2)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL >2 to WK10 1,2 (n=5,2,4,0,2)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 10 BL >2 to WK10 >-2 (n=5,2,4,0,2)	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Week 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (sleep attacks) for the assessment week was used for analysis.

Sleep attacks are uncontrollable episodes of sleep that occur during the daytime lasting a few seconds to several minutes. A questionnaire to determine sleep attacks over the prior 2 week period was administered at baseline and at 2-week intervals during the treatment period. Frequency of sleep attacks over the two-week treatment period intervals were tabulated in relation to the baseline assessment. Results are presented as participants showing the respective change in frequency of sleep attacks at baseline to the week of assessment (Week 12) (as reported by the participant). For example, someone who had >2 sleep attacks at BL who had a decrease of 1-2 by Week 12 would be reported as BL >2 to WK12 1-2. BL = baseline. WK = week.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 0 to WK12 <-2 (n=24,36,33,39,37)	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 0 to WK12 -1,-2 (n=24,36,33,39,37)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 0 to WK12 0 (n=24,36,33,39,37)	21 Participants	35 Participants	31 Participants	35 Participants	34 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 0 to WK12 1,2 (n=24,36,33,39,37)	2 Participants	1 Participants	0 Participants	3 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 0 to WK12 >-2 (n=24,36,33,39,37)	1 Participants	0 Participants	2 Participants	0 Participants	2 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 1,2 to WK12 <-2 (n=3,2,2,1,1)	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 1,2 to WK12 -1,-2 (n=3,2,2,1,1)	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 1,2 to WK12 0 (n=3,2,2,1,1)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 1,2 to WK12 1,2 (n=3,2,2,1,1)	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL 1,2 to WK12 >-2 (n=3,2,2,1,1)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL >2 to WK12 <-2 (n=4,2,4,0,2)	2 Participants	1 Participants	3 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL >2 to WK12 -1,-2 (n=4,2,4,0,2)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL >2 to WK12 0 (n=4,2,4,0,2)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL >2 to WK12 1,2 (n=4,2,4,0,2)	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Change From Baseline in Frequency of Sleep Attacks at Week 12 BL >2 to WK12 >-2 (n=4,2,4,0,2)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (UPDRS Part 1) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. Part 1 assesses mentation (4 items scored from 0 [best] to 4 [worst]; total range 0-16). Assessments were obtained at baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part 1 Week 2 (n=44,42,40,41,41)	0.1 Units on a Scale Standard Deviation 1.18	-0.2 Units on a Scale Standard Deviation 1.18	-0.2 Units on a Scale Standard Deviation 1.18	-0.5 Units on a Scale Standard Deviation 1.18	0.2 Units on a Scale Standard Deviation 1.18
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part 1 Week 4 (n=40,45,41,43,43)	-0.1 Units on a Scale Standard Deviation 1.24	0.0 Units on a Scale Standard Deviation 1.24	-0.2 Units on a Scale Standard Deviation 1.24	-0.2 Units on a Scale Standard Deviation 1.24	0.2 Units on a Scale Standard Deviation 1.24
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part 1 Week 6 (n=39,41,39,35,42)	-0.1 Units on a Scale Standard Deviation 1.16	-0.1 Units on a Scale Standard Deviation 1.16	-0.4 Units on a Scale Standard Deviation 1.16	-0.2 Units on a Scale Standard Deviation 1.16	0.3 Units on a Scale Standard Deviation 1.16
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part 1 Week 8 (n=33,42,38,37,41)	0.2 Units on a Scale Standard Deviation 1.21	-0.1 Units on a Scale Standard Deviation 1.21	-0.5 Units on a Scale Standard Deviation 1.21	-0.2 Units on a Scale Standard Deviation 1.21	0.1 Units on a Scale Standard Deviation 1.21
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part 1 Week 10 (n=32,39,37,35,41)	0.2 Units on a Scale Standard Deviation 1.19	0.1 Units on a Scale Standard Deviation 1.19	-0.5 Units on a Scale Standard Deviation 1.19	0.0 Units on a Scale Standard Deviation 1.19	-0.1 Units on a Scale Standard Deviation 1.19
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part 1 Week 12 (n=31,37,36,38,37)	0.0 Units on a Scale Standard Deviation 1.23	-0.1 Units on a Scale Standard Deviation 1.23	-0.6 Units on a Scale Standard Deviation 1.23	-0.3 Units on a Scale Standard Deviation 1.23	0.2 Units on a Scale Standard Deviation 1.23
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part 1 Endpoint (n=45,46,41,47,44)	0.1 Units on a Scale Standard Deviation 1.28	0.1 Units on a Scale Standard Deviation 1.28	-0.5 Units on a Scale Standard Deviation 1.28	-0.2 Units on a Scale Standard Deviation 1.28	0.3 Units on a Scale Standard Deviation 1.28

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (UPDRS Part 2) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. Part 2 assesses daily living (13 items scored from 0 [best] to 4 [worst]; total range 0-52). Assessments were obtained at baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=48 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=45 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=49 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=45 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in UPDRS Part 2 Week 2 (n=44,42,40,41,41)	0.0 Units on a Scale Standard Deviation 3.13	-1.0 Units on a Scale Standard Deviation 3.13	-1.0 Units on a Scale Standard Deviation 3.13	-1.2 Units on a Scale Standard Deviation 3.13	0.2 Units on a Scale Standard Deviation 3.13
Change From Baseline in UPDRS Part 2 Week 4 (n=40,45,41,43,43)	-0.6 Units on a Scale Standard Deviation 3.54	-0.4 Units on a Scale Standard Deviation 3.54	-1.8 Units on a Scale Standard Deviation 3.54	-1.7 Units on a Scale Standard Deviation 3.54	-0.8 Units on a Scale Standard Deviation 3.54
Change From Baseline in UPDRS Part 2 Week 6 (n=39,41,39,35,42)	-1.0 Units on a Scale Standard Deviation 3.37	-1.3 Units on a Scale Standard Deviation 3.37	-1.8 Units on a Scale Standard Deviation 3.37	-0.3 Units on a Scale Standard Deviation 3.37	-0.7 Units on a Scale Standard Deviation 3.37
Change From Baseline in UPDRS Part 2 Week 8 (n=33,42,38,37,41)	-0.2 Units on a Scale Standard Deviation 3.27	-0.9 Units on a Scale Standard Deviation 3.27	-2.2 Units on a Scale Standard Deviation 3.27	-1.8 Units on a Scale Standard Deviation 3.27	-0.9 Units on a Scale Standard Deviation 3.27
Change From Baseline in UPDRS Part 2 Week 10 (n=32,39,37,35,41)	-0.4 Units on a Scale Standard Deviation 3.63	-0.8 Units on a Scale Standard Deviation 3.63	-2.0 Units on a Scale Standard Deviation 3.63	-0.8 Units on a Scale Standard Deviation 3.63	-0.6 Units on a Scale Standard Deviation 3.63
Change From Baseline in UPDRS Part 2 Week 12 (n=31,37,36,38,37)	-0.4 Units on a Scale Standard Deviation 3.48	-1.1 Units on a Scale Standard Deviation 3.48	-2.7 Units on a Scale Standard Deviation 3.48	-0.8 Units on a Scale Standard Deviation 3.48	-0.8 Units on a Scale Standard Deviation 3.48
Change From Baseline in UPDRS Part 2 Endpoint (n=45,46,41,47,44)	-0.3 Units on a Scale Standard Deviation 3.61	-0.9 Units on a Scale Standard Deviation 3.61	-2.5 Units on a Scale Standard Deviation 3.61	-0.9 Units on a Scale Standard Deviation 3.61	-1.0 Units on a Scale Standard Deviation 3.61

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 1 hour postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (UPDRS Part 3) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. The Part 3 subscale assesses motor function across 14 categories for 27 items. Scores for each item range from 0 (best) to 4 (worst) with a total range of 0-108. Assessments were obtained at baseline (predose Day 1) and 1 hour postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=47 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=43 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=53 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=47 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in UPDRS Part 3 (1 Hour Post-dose) Week 2 (n=42,40,37,39,43)	-1.1 Units on a Scale Standard Deviation 8.49	-1.4 Units on a Scale Standard Deviation 8.49	-0.9 Units on a Scale Standard Deviation 8.49	-5.8 Units on a Scale Standard Deviation 8.49	-2.7 Units on a Scale Standard Deviation 8.49
Change From Baseline in UPDRS Part 3 (1 Hour Post-dose) Week 4 (n=40,44,40,43,43)	-3.3 Units on a Scale Standard Deviation 8.52	-2.4 Units on a Scale Standard Deviation 8.52	-3.7 Units on a Scale Standard Deviation 8.52	-5.8 Units on a Scale Standard Deviation 8.52	-1.0 Units on a Scale Standard Deviation 8.52
Change From Baseline in UPDRS Part 3 (1 Hour Post-dose) Week 6 (n=39,41,38,33,41)	-1.2 Units on a Scale Standard Deviation 8.63	-3.3 Units on a Scale Standard Deviation 8.63	-3.4 Units on a Scale Standard Deviation 8.63	-4.3 Units on a Scale Standard Deviation 8.63	-2.4 Units on a Scale Standard Deviation 8.63
Change From Baseline in UPDRS Part 3 (1 Hour Post-dose) Week 8 (n=31,42,36,35,41)	-2.1 Units on a Scale Standard Deviation 8.82	-2.7 Units on a Scale Standard Deviation 8.82	-5.1 Units on a Scale Standard Deviation 8.82	-6.8 Units on a Scale Standard Deviation 8.82	-3.8 Units on a Scale Standard Deviation 8.82
Change From Baseline in UPDRS Part 3 (1 Hour Post-dose) Week 10 (n=31,38,36,34,41)	-2.9 Units on a Scale Standard Deviation 8.76	-5.3 Units on a Scale Standard Deviation 8.76	-4.1 Units on a Scale Standard Deviation 8.76	-5.0 Units on a Scale Standard Deviation 8.76	-1.6 Units on a Scale Standard Deviation 8.76
Change From Baseline in UPDRS Part 3 (1 Hour Post-dose) Week 12 (n=30,39,35,38,40)	-2.2 Units on a Scale Standard Deviation 9.16	-3.3 Units on a Scale Standard Deviation 9.16	-4.0 Units on a Scale Standard Deviation 9.16	-5.2 Units on a Scale Standard Deviation 9.16	-3.0 Units on a Scale Standard Deviation 9.16
Change From Baseline in UPDRS Part 3 (1 Hour Post-dose) Endpoint (n=47,47,43,53,47)	-1.9 Units on a Scale Standard Deviation 9.32	-2.3 Units on a Scale Standard Deviation 9.32	-3.8 Units on a Scale Standard Deviation 9.32	-5.5 Units on a Scale Standard Deviation 9.32	-2.2 Units on a Scale Standard Deviation 9.32

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline data (UPDRS Part 3) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. The Part 3 subscale assesses motor function across 14 categories for 27 items. Scores for each item range from 0 (best) to 4 (worst) with a total range of 0-108. Assessments were obtained at baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled standard deviation were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Outcome measures

Measure	Preladenant 1 mg BID n=47 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=47 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=43 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=53 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=47 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in UPDRS Part 3 (2 Hours Post-dose) Week 2 (n=44,44,41,44,44)	-2.7 Units on a Scale Standard Deviation 8.04	-2.9 Units on a Scale Standard Deviation 8.04	-3.5 Units on a Scale Standard Deviation 8.04	-5.1 Units on a Scale Standard Deviation 8.04	-2.6 Units on a Scale Standard Deviation 8.04
Change From Baseline in UPDRS Part 3 (2 Hours Post-dose) Week 4 (n=40,45,41,43,43)	-3.2 Units on a Scale Standard Deviation 8.48	-1.5 Units on a Scale Standard Deviation 8.48	-4.0 Units on a Scale Standard Deviation 8.48	-6.0 Units on a Scale Standard Deviation 8.48	-2.9 Units on a Scale Standard Deviation 8.48
Change From Baseline in UPDRS Part 3 (2 Hours Post-dose) Week 6 (n=38,41,39,34,42)	-2.5 Units on a Scale Standard Deviation 8.31	-2.4 Units on a Scale Standard Deviation 8.31	-4.0 Units on a Scale Standard Deviation 8.31	-6.4 Units on a Scale Standard Deviation 8.31	-2.5 Units on a Scale Standard Deviation 8.31
Change From Baseline in UPDRS Part 3 (2 Hours Post-dose) Week 8 (n=33,42,38,37,41)	-1.9 Units on a Scale Standard Deviation 8.85	-1.7 Units on a Scale Standard Deviation 8.85	-5.7 Units on a Scale Standard Deviation 8.85	-6.9 Units on a Scale Standard Deviation 8.85	-5.6 Units on a Scale Standard Deviation 8.85
Change From Baseline in UPDRS Part 3 (2 Hours Post-dose) Week 10 (n=32,39,37,35,41)	-3.5 Units on a Scale Standard Deviation 8.40	-4.3 Units on a Scale Standard Deviation 8.40	-5.2 Units on a Scale Standard Deviation 8.40	-5.6 Units on a Scale Standard Deviation 8.40	-3.4 Units on a Scale Standard Deviation 8.40
Change From Baseline in UPDRS Part 3 (2 Hours Post-dose) Week 12 (n=31,39,36,39,40)	-2.7 Units on a Scale Standard Deviation 8.84	-3.1 Units on a Scale Standard Deviation 8.84	-7.3 Units on a Scale Standard Deviation 8.84	-6.8 Units on a Scale Standard Deviation 8.84	-4.5 Units on a Scale Standard Deviation 8.84
Change From Baseline in UPDRS Part 3 (2 Hours Post-dose) Endpoint (n=47,47,43,53,47)	-3.0 Units on a Scale Standard Deviation 9.09	-2.8 Units on a Scale Standard Deviation 9.09	-5.9 Units on a Scale Standard Deviation 9.09	-6.3 Units on a Scale Standard Deviation 9.09	-3.1 Units on a Scale Standard Deviation 9.09

SECONDARY outcome

Timeframe: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12

Population: The Efficacy Population consisting of all treated participants who had post-baseline date (UPDRS Part 4) for the assessment week was used for analysis.

The UPDRS is a frequently used multi-item 4-part questionnaire designed to assess various aspects of Parkinson's disease severity. A total of 42 items are assessed divided across Parts 1 to 4. The Part 4 subscale assesses complications of therapy over the past week for a total of eleven question items. The first three questions and question 8 are rated from 0 (best) to 4 (worst), and the remaining seven questions are simple no (0) / yes (1) questions. The total subscale score ranges from 0 to 23. Assessments were obtained at baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, and 12. For endpoint, the last postbaseline visit while on study medication was used. Change from baseline in LS means and pooled SD were obtained from an ANCOVA model with effect for treatment and baseline covariate. Negative change from baseline indicates a decrease in severity.

Outcome measures

Measure	Preladenant 1 mg BID n=45 Participants Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=46 Participants Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=41 Participants Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=47 Participants Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=44 Participants Participants received preladenant matching placebo BID during the 12-week treatment period.
Change From Baseline in UPDRS Part 4 Week 2 (n=44,42,40,41,41)	-0.3 Units on a Scale Standard Deviation 1.62	-0.5 Units on a Scale Standard Deviation 1.62	-0.4 Units on a Scale Standard Deviation 1.62	-0.5 Units on a Scale Standard Deviation 1.62	-0.8 Units on a Scale Standard Deviation 1.62
Change From Baseline in UPDRS Part 4 Week 4 (n=40,45,41,43,43)	-0.4 Units on a Scale Standard Deviation 1.71	-0.8 Units on a Scale Standard Deviation 1.71	-0.4 Units on a Scale Standard Deviation 1.71	-0.5 Units on a Scale Standard Deviation 1.71	-0.3 Units on a Scale Standard Deviation 1.71
Change From Baseline in UPDRS Part 4 Week 6 (n=39,41,39,35,42)	-0.8 Units on a Scale Standard Deviation 1.75	-0.4 Units on a Scale Standard Deviation 1.75	-0.3 Units on a Scale Standard Deviation 1.75	-0.2 Units on a Scale Standard Deviation 1.75	-0.7 Units on a Scale Standard Deviation 1.75
Change From Baseline in UPDRS Part 4 Week 8 (n=33,42,38,37,41)	-0.7 Units on a Scale Standard Deviation 2.07	-0.8 Units on a Scale Standard Deviation 2.07	-1.0 Units on a Scale Standard Deviation 2.07	-0.1 Units on a Scale Standard Deviation 2.07	-0.8 Units on a Scale Standard Deviation 2.07
Change From Baseline in UPDRS Part 4 Week 10 (n=32,39,37,35,41)	-0.8 Units on a Scale Standard Deviation 1.95	-0.4 Units on a Scale Standard Deviation 1.95	-0.7 Units on a Scale Standard Deviation 1.95	-0.6 Units on a Scale Standard Deviation 1.95	-0.3 Units on a Scale Standard Deviation 1.95
Change From Baseline in UPDRS Part 4 Week 12 (n=31,37,36,38,37)	-1.1 Units on a Scale Standard Deviation 2.05	0.0 Units on a Scale Standard Deviation 2.05	-1.2 Units on a Scale Standard Deviation 2.05	-0.7 Units on a Scale Standard Deviation 2.05	-0.9 Units on a Scale Standard Deviation 2.05
Change From Baseline in UPDRS Part 4 Endpoint (n=45,46,41,47,44)	-0.8 Units on a Scale Standard Deviation 1.95	-0.4 Units on a Scale Standard Deviation 1.95	-0.8 Units on a Scale Standard Deviation 1.95	-0.7 Units on a Scale Standard Deviation 1.95	-0.9 Units on a Scale Standard Deviation 1.95

Adverse Events

Preladenant 1 mg BID

Serious events: 4 serious events

Other events: 30 other events

Deaths: 0 deaths

Preladenant 2 mg BID

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Preladenant 5 mg BID

Serious events: 1 serious events

Other events: 34 other events

Deaths: 0 deaths

Preladenant 10 mg BID

Serious events: 3 serious events

Other events: 37 other events

Deaths: 0 deaths

Placebo BID

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Measure	Preladenant 1 mg BID n=49 participants at risk Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=49 participants at risk Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=47 participants at risk Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=54 participants at risk Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=47 participants at risk Participants received preladenant matching placebo BID during the 12-week treatment period.
Cardiac disorders ANGINA PECTORIS	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	1.9% 1/54 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Cardiac disorders CORONARY ARTERY DISEASE	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	1.9% 1/54 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Cardiac disorders SICK SINUS SYNDROME	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Gastrointestinal disorders INTESTINAL OBSTRUCTION	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
General disorders CONDITION AGGRAVATED	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	1.9% 1/54 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Infections and infestations PNEUMONIA	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	1.9% 1/54 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Infections and infestations URINARY TRACT INFECTION	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Injury, poisoning and procedural complications OVERDOSE	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders CEREBROVASCULAR ACCIDENT	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders LOSS OF CONSCIOUSNESS	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders PARKINSON'S DISEASE	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Psychiatric disorders HALLUCINATION, VISUAL	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Psychiatric disorders SUICIDE ATTEMPT	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	1.9% 1/54 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).

Other adverse events

Measure	Preladenant 1 mg BID n=49 participants at risk Participants received preladenant 1 mg BID during the 12-week treatment period.	Preladenant 2 mg BID n=49 participants at risk Participants received preladenant 2 mg BID during the 12-week treatment period.	Preladenant 5 mg BID n=47 participants at risk Participants received preladenant 5 mg BID during the 12-week treatment period.	Preladenant 10 mg BID n=54 participants at risk Participants received preladenant 10 mg BID during the 12-week treatment period.	Placebo BID n=47 participants at risk Participants received preladenant matching placebo BID during the 12-week treatment period.
Gastrointestinal disorders CONSTIPATION	12.2% 6/49 • Number of events 7 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	12.8% 6/47 • Number of events 6 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	3.7% 2/54 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Gastrointestinal disorders DIARRHOEA	4.1% 2/49 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	4.3% 2/47 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	3.7% 2/54 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.5% 4/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Gastrointestinal disorders NAUSEA	10.2% 5/49 • Number of events 7 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.2% 4/49 • Number of events 5 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	12.8% 6/47 • Number of events 6 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	3.7% 2/54 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	10.6% 5/47 • Number of events 5 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
General disorders ASTHENIA	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	1.9% 1/54 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
General disorders FATIGUE	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	5.6% 3/54 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
General disorders GAIT DISTURBANCE	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	1.9% 1/54 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Infections and infestations NASOPHARYNGITIS	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Infections and infestations URINARY TRACT INFECTION	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	7.4% 4/54 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Injury, poisoning and procedural complications CONTUSION	4.1% 2/49 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	4.3% 2/47 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Injury, poisoning and procedural complications FALL	8.2% 4/49 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.2% 4/49 • Number of events 17 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	5.6% 3/54 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	12.8% 6/47 • Number of events 11 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Investigations BLOOD CREATINE PHOSPHOKINASE INCREASED	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Investigations C-REACTIVE PROTEIN INCREASED	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	1.9% 1/54 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	4.3% 2/47 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Investigations WEIGHT DECREASED	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	7.4% 4/54 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Musculoskeletal and connective tissue disorders ARTHRALGIA	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	4.1% 2/49 • Number of events 5 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	3.7% 2/54 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Musculoskeletal and connective tissue disorders BACK PAIN	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	3.7% 2/54 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	3.7% 2/54 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	4.1% 2/49 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders DIZZINESS	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.2% 4/49 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	11.1% 6/54 • Number of events 7 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders DYSKINESIA	8.2% 4/49 • Number of events 6 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.5% 4/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	13.0% 7/54 • Number of events 8 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	12.8% 6/47 • Number of events 6 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders DYSTONIA	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.0% 1/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	3.7% 2/54 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	2.1% 1/47 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders HEADACHE	10.2% 5/49 • Number of events 10 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	4.1% 2/49 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.5% 4/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	5.6% 3/54 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.5% 4/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders PARKINSON'S DISEASE	10.2% 5/49 • Number of events 5 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	10.6% 5/47 • Number of events 7 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	14.8% 8/54 • Number of events 9 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders SOMNOLENCE	10.2% 5/49 • Number of events 6 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.2% 4/49 • Number of events 5 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.5% 4/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	13.0% 7/54 • Number of events 7 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Nervous system disorders TREMOR	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	3.7% 2/54 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	4.3% 2/47 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Psychiatric disorders INSOMNIA	6.1% 3/49 • Number of events 3 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.1% 3/49 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.5% 4/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	9.3% 5/54 • Number of events 5 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	8.5% 4/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Vascular disorders HOT FLUSH	6.1% 3/49 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/49 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/54 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	0.00% 0/47 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).
Vascular disorders HYPERTENSION	2.0% 1/49 • Number of events 1 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	4.1% 2/49 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	6.4% 3/47 • Number of events 4 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	3.7% 2/54 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).	4.3% 2/47 • Number of events 2 • Up to 18 weeks The Safety Population consisted of all participants who received at least one dose of study medication (either preladenant or placebo).

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator agrees not to publish or publicly present any interim results of the study without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.
• Publication restrictions are in place

Restriction type: OTHER