Trial Outcomes & Findings for Reducing Involuntary Movements in Participants With Tardive Dyskinesia (NCT NCT02198794)

NCT ID: NCT02198794

Last Updated: 2022-04-01

Results Overview

AEs were analyzed as one group combined for parts A and B per planned analysis. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE=prevents normal daily activities. Drug-related TEAEs: TEAEs with possible, probable, or definite relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A treatment-emergent AE was defined as an AE that began after the first administration of study medication or existing AEs that worsened after the first dose of study medication. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

343 participants

Primary outcome timeframe

Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days)

Results posted on

2022-04-01

Participant Flow

343 participants who completed previous SD-809 studies, including study SD-809-C-18 (NCT02195700) or SD-809-C-23 (NCT02291861) were enrolled and 337 participants were eligible for analysis. 6 participants were not evaluable and were excluded from the analysis due to site data integrity issues as reported to the United States Food and Drug Administration (US FDA).

Study included 3 parts: A, B, and C. Participants in Part A who were on a stable dose for ≥4 weeks after a 6-week titration, were invited to participate in Part B. Participants who are noted as "Completed" for Part A: completed the study in Part A plus continued in Part B. EU participants who completed Part B were invited to participate in Part C.

Participant milestones

Participant milestones
Measure	SD-809 Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part B: Placebo Participants received placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter received SD-809 (stable dose) for 12 weeks.	Part B: SD-809 Participants received SD-809 (stable dose) for 1 week in randomized withdrawal period and continued to receive the same dose of SD-809 for an additional 12 weeks.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Open-Label (158 Weeks) STARTED	337	0	0	0
Part A: Open-Label (158 Weeks) Received at Least 1 Dose of Study Drug	337	0	0	0
Part A: Open-Label (158 Weeks) Intent-to-Treat (ITT) Population	337	0	0	0
Part A: Open-Label (158 Weeks) Participants Who Participated in Part A But Not in Part B	195	0	0	0
Part A: Open-Label (158 Weeks) Participants Who Agreed to Continue in Part B	142	0	0	0
Part A: Open-Label (158 Weeks) COMPLETED	32	0	0	0
Part A: Open-Label (158 Weeks) NOT COMPLETED	305	0	0	0
Part B: Randomized (13 Weeks) STARTED	0	71	71	0
Part B: Randomized (13 Weeks) Randomized Withdrawal mITT Population	0	63	65	0
Part B: Randomized (13 Weeks) COMPLETED	0	66	68	0
Part B: Randomized (13 Weeks) NOT COMPLETED	0	5	3	0
Part C: Safety Assessment (52 Weeks) STARTED	0	0	0	80
Part C: Safety Assessment (52 Weeks) COMPLETED	0	0	0	73
Part C: Safety Assessment (52 Weeks) NOT COMPLETED	0	0	0	7

Reasons for withdrawal

Reasons for withdrawal
Measure	SD-809 Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part B: Placebo Participants received placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter received SD-809 (stable dose) for 12 weeks.	Part B: SD-809 Participants received SD-809 (stable dose) for 1 week in randomized withdrawal period and continued to receive the same dose of SD-809 for an additional 12 weeks.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Open-Label (158 Weeks) Withdrawal by Subject	79	0	0	0
Part A: Open-Label (158 Weeks) Adverse Event	33	0	0	0
Part A: Open-Label (158 Weeks) Lost to Follow-up	24	0	0	0
Part A: Open-Label (158 Weeks) Lack of Efficacy	9	0	0	0
Part A: Open-Label (158 Weeks) Death	8	0	0	0
Part A: Open-Label (158 Weeks) Noncompliance with study drug	3	0	0	0
Part A: Open-Label (158 Weeks) Other than specified	5	0	0	0
Part A: Open-Label (158 Weeks) Study terminated	1	0	0	0
Part A: Open-Label (158 Weeks) Protocol deviation	1	0	0	0
Part A: Open-Label (158 Weeks) Agreed to continue in Part B	142	0	0	0
Part B: Randomized (13 Weeks) Withdrawal by Subject	0	3	1	0
Part B: Randomized (13 Weeks) Lost to Follow-up	0	2	2	0
Part C: Safety Assessment (52 Weeks) Withdrawal by Subject	0	0	0	3
Part C: Safety Assessment (52 Weeks) Adverse Event	0	0	0	2
Part C: Safety Assessment (52 Weeks) Death	0	0	0	2

Baseline Characteristics

Reducing Involuntary Movements in Participants With Tardive Dyskinesia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SD-809 n=337 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.
Age, Continuous	56.9 years STANDARD_DEVIATION 10.65 • n=5 Participants
Sex: Female, Male Female	188 Participants n=5 Participants
Sex: Female, Male Male	149 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	300 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaskan Native	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black	69 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	264 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants
Total Motor Abnormal Involuntary Movement Scale (AIMS) Score	10.7 units on a scale STANDARD_DEVIATION 4.68 • n=5 Participants
AIMS Individual Items (8-10) Scores Severity of abnormal movements	2.6 units on a scale STANDARD_DEVIATION 0.78 • n=5 Participants
AIMS Individual Items (8-10) Scores Incapacitation due to abnormal movements	2.0 units on a scale STANDARD_DEVIATION 1.07 • n=5 Participants
AIMS Individual Items (8-10) Scores Participant's awareness of abnormal movements	2.2 units on a scale STANDARD_DEVIATION 1.08 • n=5 Participants
Modified Craniocervical Dystonia Questionnaire 24 (CDQ-24) Score	29.2 units on a scale STANDARD_DEVIATION 18.96 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days)

Population: Safety population included all participants who were administered any study drug.

Outcome measures

Outcome measures
Measure	SD-809 n=337 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 n=80 Participants EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal Any TEAEs	269 Participants	23 Participants
Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal Serious TEAEs	68 Participants	5 Participants
Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal Severe TEAEs	57 Participants	3 Participants
Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal Drug-Related TEAEs	154 Participants	3 Participants
Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal TEAEs Leading to Withdrawal From Study	42 Participants	3 Participants

PRIMARY outcome

Timeframe: Day 1 of Part B, Day 7 of Part B

Population: The randomized withdrawal modified intent-to-treat (mITT) population included all participants enrolled in Part B who received study drug during the randomized withdrawal period and had a total motor AIMS score as assessed by blinded central video rating at both the pre-withdrawal visit and the post-withdrawal visit.

The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

Outcome measures

Outcome measures
Measure	SD-809 n=63 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 n=65 Participants EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part B: Change From Day 1 Visit in Total Motor AIMS Score at Day 7 Visit, as Assessed by Blinded Central Video Rating Pre-withdrawal	5.7 units on a scale Standard Error 0.55	5.0 units on a scale Standard Error 0.49
Part B: Change From Day 1 Visit in Total Motor AIMS Score at Day 7 Visit, as Assessed by Blinded Central Video Rating Change at Post-withdrawal	0.6 units on a scale Standard Error 0.28	0 units on a scale Standard Error 0.29

SECONDARY outcome

Timeframe: Baseline, Week 145

Population: The ITT population included all participants who were enrolled in the study, regardless of whether or not a participant received a dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

The AIMS is an assessment tool used to detect and follow the severity of tardive dyskinesia (TD) over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

Outcome measures

Outcome measures
Measure	SD-809 n=160 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating	-6.6 units on a scale Standard Error 0.37	—

SECONDARY outcome

Timeframe: Baseline, Week 158

Outcome measures

Outcome measures
Measure	SD-809 n=34 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating	-6.3 units on a scale Standard Error 0.85	—

SECONDARY outcome

Timeframe: Baseline, Week 145

Outcome measures

Outcome measures
Measure	SD-809 n=159 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating	-57.0 percent change Standard Error 2.43	—

SECONDARY outcome

Timeframe: Baseline, Week 158

Outcome measures

Outcome measures
Measure	SD-809 n=34 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating	-54.9 percent change Standard Error 6.76	—

SECONDARY outcome

Timeframe: Baseline to Week 145

Outcome measures

Outcome measures
Measure	SD-809 n=159 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Percentage of Participants Who Had a 50% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating	67 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to Week 145

Outcome measures

Outcome measures
Measure	SD-809 n=159 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Percentage of Participants Who Had a 70% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating	42 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, Week 145

The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. Items 8 to 10 deal with global severity as judged by the examiner, and the participant's awareness of the movements and the distress associated with them. Item 8 (used as an overall severity index indicating severity of abnormal movements) was rated on a 5-point anchored scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 9 and 10 (provide additional information with regard to participant's incapacitation due to abnormal movements and participant's awareness of abnormal movements) were rated on a 5-point anchored scale ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Higher scores indicated more severe disease.

Outcome measures

Outcome measures
Measure	SD-809 n=160 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Change From Baseline in AIMS Items 8, 9, and 10 Score at Week 145, as Assessed by the Site Rating Severity of abnormal movements	-1.3 units on a scale Standard Error 0.07	—
Part A: Change From Baseline in AIMS Items 8, 9, and 10 Score at Week 145, as Assessed by the Site Rating Incapacitation due to abnormal movements	-1.3 units on a scale Standard Error 0.08	—
Part A: Change From Baseline in AIMS Items 8, 9, and 10 Score at Week 145, as Assessed by the Site Rating Participant's awareness of abnormal movements	-1.3 units on a scale Standard Error 0.09	—

SECONDARY outcome

Timeframe: Baseline up to Week 145

A treatment success was defined as much or very much improved on the CGIC from baseline of this study. The CGIC is a single-item questionnaire that asks the investigator to assess a participant's TD symptoms at specific visits/weeks after initiating therapy. The CGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.

Outcome measures

Outcome measures
Measure	SD-809 n=160 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Percentage of Participants Who Were a Treatment Success, Based on the Clinical Global Impression of Change (CGIC)	73 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline up to Week 145

A treatment success was defined as much or very much improved on the PGIC from baseline of this study. The PGIC is single-item questionnaire that asks the participant to assess their TD symptoms at specific visits/weeks after initiating therapy. The PGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.

Outcome measures

Outcome measures
Measure	SD-809 n=161 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Percentage of Participants Who Were a Treatment Success, Based on the Patient Global Impression of Change (PGIC)	63 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, Week 158

The CDQ-24 is a disease-specific quality of life questionnaire developed for use in participants with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ-24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. The following domains were evaluated in the mCDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by participants on a scale of 0 = never or no impairment to 4 = always or very severe impairment. Total score ranged from 0 - 96, with higher score indicative of severe impairment.

Outcome measures

Outcome measures
Measure	SD-809 n=39 Participants Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158.	Part C: SD-809 EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Part A: Change From Baseline in Modified CDQ-24 Score at Week 158	-6.3 units on a scale Standard Error 2.61	—

Adverse Events

Part A and Part B Participants

Serious events: 68 serious events

Other events: 172 other events

Deaths: 8 deaths

Part C: SD-809

Serious events: 5 serious events

Other events: 5 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Part A and Part B Participants n=337 participants at risk Participants received SD-809 orally BID starting at 12 mg/day, which was titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who declined to participate in Part B, continued at their stable dose of SD-809 BID up to Week 158. Participants who agreed to participate in Part B, received SD-809 or placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter received SD-809 (stable dose) for 12 weeks.	Part C: SD-809 n=80 participants at risk EU participants who completed Part B and were willing to continue in the study continued treatment with SD-809 for 52 weeks at the current dose administered during the 12-week open-label period of Part B.
Gastrointestinal disorders Diarrhoea	8.0% 27/337 • Number of events 32 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	0.00% 0/80 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Infections and infestations Nasopharyngitis	5.9% 20/337 • Number of events 28 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	2.5% 2/80 • Number of events 2 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Infections and infestations Urinary tract infection	9.2% 31/337 • Number of events 56 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	0.00% 0/80 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Injury, poisoning and procedural complications Fall	5.3% 18/337 • Number of events 23 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	0.00% 0/80 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Investigations Weight decreased	9.5% 32/337 • Number of events 34 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	0.00% 0/80 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Nervous system disorders Dyskinesia	6.5% 22/337 • Number of events 29 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	2.5% 2/80 • Number of events 2 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Nervous system disorders Headache	7.1% 24/337 • Number of events 31 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	0.00% 0/80 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Nervous system disorders Somnolence	10.1% 34/337 • Number of events 41 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	0.00% 0/80 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Psychiatric disorders Anxiety	12.2% 41/337 • Number of events 51 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	0.00% 0/80 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Psychiatric disorders Depression	10.4% 35/337 • Number of events 45 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	0.00% 0/80 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.
Vascular disorders Hypertension	6.8% 23/337 • Number of events 25 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.	1.2% 1/80 • Number of events 1 • Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days) Adverse events were analyzed as one group combined for Parts A and B and as a separate group for Part C per planned analysis.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products R&D, Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER