Trial Outcomes & Findings for Aim to Reduce Movements in Tardive Dyskinesia (NCT NCT02195700)

NCT ID: NCT02195700

Last Updated: 2021-11-09

Results Overview

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. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders. This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement. A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point, treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. An unstructured covariance model was used.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

117 participants

Primary outcome timeframe

Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12

Results posted on

2021-11-09

Participant Flow

202 patients were screened and gave informed consent to enter the study. 85 were either ineligible for entry into the study or declined study participation. The most common reason for ineligibility (49 patients) was insufficient TD severity as assessed with Abnormal Involuntary Movement Scale (AIMS). 117 patients were randomized.

Participant milestones

Participant milestones
Measure	SD-809 Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Study STARTED	58	59
Overall Study Safety and ITT Populations	58	59
Overall Study Modified ITT Population	56	57
Overall Study Maintenance Period	53	54
Overall Study COMPLETED	52	52
Overall Study NOT COMPLETED	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	SD-809 Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Overall Study Protocol Violation	0	2
Overall Study Noncompliance	1	0
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	3	2
Overall Study Lost to Follow-up	1	1

Baseline Characteristics

Central reading was not available for one placebo patient.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SD-809 n=58 Participants Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=59 Participants Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Total n=117 Participants Total of all reporting groups
Age, Continuous	55.9 years STANDARD_DEVIATION 9.82 • n=58 Participants	53.3 years STANDARD_DEVIATION 10.64 • n=59 Participants	54.6 years STANDARD_DEVIATION 10.28 • n=117 Participants
Sex: Female, Male Female	29 Participants n=58 Participants	32 Participants n=59 Participants	61 Participants n=117 Participants
Sex: Female, Male Male	29 Participants n=58 Participants	27 Participants n=59 Participants	56 Participants n=117 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=58 Participants	11 Participants n=59 Participants	15 Participants n=117 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	53 Participants n=58 Participants	47 Participants n=59 Participants	100 Participants n=117 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=58 Participants	1 Participants n=59 Participants	2 Participants n=117 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=58 Participants	0 Participants n=59 Participants	0 Participants n=117 Participants
Race (NIH/OMB) Asian	2 Participants n=58 Participants	1 Participants n=59 Participants	3 Participants n=117 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=58 Participants	0 Participants n=59 Participants	0 Participants n=117 Participants
Race (NIH/OMB) Black or African American	19 Participants n=58 Participants	14 Participants n=59 Participants	33 Participants n=117 Participants
Race (NIH/OMB) White	37 Participants n=58 Participants	44 Participants n=59 Participants	81 Participants n=117 Participants
Race (NIH/OMB) More than one race	0 Participants n=58 Participants	0 Participants n=59 Participants	0 Participants n=117 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=58 Participants	0 Participants n=59 Participants	0 Participants n=117 Participants
Education Level =12 years or fewer of formal education	30 Participants n=58 Participants	30 Participants n=59 Participants	60 Participants n=117 Participants
Education Level >12 years of formal education	28 Participants n=58 Participants	29 Participants n=59 Participants	57 Participants n=117 Participants
Weight	86.94 kg STANDARD_DEVIATION 24.081 • n=58 Participants	84.95 kg STANDARD_DEVIATION 20.975 • n=59 Participants	85.94 kg STANDARD_DEVIATION 22.493 • n=117 Participants
Height	169.23 cm STANDARD_DEVIATION 11.462 • n=58 Participants	169.72 cm STANDARD_DEVIATION 10.098 • n=59 Participants	169.48 cm STANDARD_DEVIATION 10.752 • n=117 Participants
Body Mass Index	30.35 kg/m^2 STANDARD_DEVIATION 7.926 • n=58 Participants	29.45 kg/m^2 STANDARD_DEVIATION 6.958 • n=59 Participants	29.89 kg/m^2 STANDARD_DEVIATION 7.435 • n=117 Participants
Using a Dopamine Receptor Antagonist (DRA) Yes	45 Participants n=58 Participants	49 Participants n=59 Participants	94 Participants n=117 Participants
Using a Dopamine Receptor Antagonist (DRA) No	13 Participants n=58 Participants	10 Participants n=59 Participants	23 Participants n=117 Participants
Duration of tardive dyskinesia	72.6 months STANDARD_DEVIATION 81.65 • n=58 Participants	76.8 months STANDARD_DEVIATION 82.05 • n=59 Participants	74.7 months STANDARD_DEVIATION 81.53 • n=117 Participants
Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score	9.6 units on a scale STANDARD_DEVIATION 4.07 • n=58 Participants • Central reading was not available for one placebo patient.	9.6 units on a scale STANDARD_DEVIATION 3.77 • n=58 Participants • Central reading was not available for one placebo patient.	9.6 units on a scale STANDARD_DEVIATION 3.90 • n=116 Participants • Central reading was not available for one placebo patient.
Modified Craniocervical Dystonia Questionnaire (CDQ-24)	38.4 units on a scale STANDARD_DEVIATION 20.41 • n=58 Participants • Baseline CDQ-24 was not completed by two placebo patients.	39.7 units on a scale STANDARD_DEVIATION 18.17 • n=57 Participants • Baseline CDQ-24 was not completed by two placebo patients.	39.1 units on a scale STANDARD_DEVIATION 19.26 • n=115 Participants • Baseline CDQ-24 was not completed by two placebo patients.

PRIMARY outcome

Timeframe: Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12

Population: The Modified ITT (mITT) Population was defined as all patients in the ITT Population who received study drug and had at least 1 centrally read post-baseline assessment of the AIMS from at least 1 scheduled post-baseline time point. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.

Outcome measures

Outcome measures
Measure	SD-809 n=52 Participants Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=51 Participants Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis	-3.0 units on a scale Standard Error 0.45	-1.6 units on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: Week 12

Population: modified intent to treat population

The CGIC is a single-item questionnaire that asks the investigator to assess a patient's TD symptoms at specific visits after initiating therapy. The CGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as "much improved" or "very much improved" at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not "much improved" or "very much improved" at the week 12 visit, were considered treatment failures.

Outcome measures

Outcome measures
Measure	SD-809 n=56 Participants Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=57 Participants Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)	48.2 percentage of participants	40.4 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: modified intent to treat population

The PGIC is a single-item questionnaire that asks the patient to assess their TD symptoms at specific visits after initiating therapy. The PGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as "much improved" or "very much improved" at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not "much improved" or "very much improved" at the week 12 visit, were considered treatment failures.

Outcome measures

Outcome measures
Measure	SD-809 n=56 Participants Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=57 Participants Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)	42.9 percentage of participants	29.8 percentage of participants

SECONDARY outcome

Timeframe: Day 0 (Baseline), Week 12 with last observation carried forward

Population: modified intent to treat population

The CDQ-24 is a disease-specific quality of life questionnaire developed for use in patients 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 are evaluated in the CDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 (no impairment) to 96 (severe impairment). Negative change from baseline scores indicate improvement.

Outcome measures

Outcome measures
Measure	SD-809 n=56 Participants Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=57 Participants Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Change From Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24)	-11.1 units on a scale Standard Error 2.14	-8.3 units on a scale Standard Error 2.31

SECONDARY outcome

Timeframe: Day 1 to Week 12

Population: Safety population

An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator and includes possibly, probably and definitely related categories. Serious AEs (SAE) include death, a life-threatening adverse event, 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 the patient and required medical intervention to prevent the previously listed serious outcomes.

Outcome measures

Outcome measures
Measure	SD-809 n=58 Participants Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=59 Participants Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Participants With Adverse Events for the Overall Treatment Period Overall Treatment Period: any AE	41 Participants	36 Participants
Participants With Adverse Events for the Overall Treatment Period Overall Treatment Period: SAE	3 Participants	5 Participants
Participants With Adverse Events for the Overall Treatment Period Overall Treatment Period: Severe AE	3 Participants	3 Participants
Participants With Adverse Events for the Overall Treatment Period Overall Treatment Period: treatment-related AE	28 Participants	21 Participants
Participants With Adverse Events for the Overall Treatment Period Overall Treatment Period: Deaths	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12

Population: modified intent to treat population. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.

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. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders. This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative percent change from baseline score indicates improvement. The MMRM model includes fixed effects for treatment, time point (weeks 2, 4, 6, 9, 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. Patient is a random effect.

Outcome measures

Outcome measures
Measure	SD-809 n=52 Participants Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=51 Participants Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Percentage Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis	-26.7 percentage change Standard Error 6.06	-15.5 percentage change Standard Error 6.26

SECONDARY outcome

Timeframe: Day 0 (Baseline), Week 12

Population: modified intent to treat population.

Response level represents the % improvement in AIMS from baseline. 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. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders. This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). Patients with a missing AIMS score were considered to be AIMS nonresponders.

Outcome measures

Outcome measures
Measure	SD-809 n=56 Participants Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=57 Participants Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 >=10%	69.6 percentage of participants	42.1 percentage of participants
Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 >=20%	50.0 percentage of participants	29.8 percentage of participants
Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 >=30%	46.4 percentage of participants	24.6 percentage of participants
Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 >=40%	32.1 percentage of participants	22.8 percentage of participants
Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 >=50%	23.2 percentage of participants	17.5 percentage of participants
Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 >=60%	19.6 percentage of participants	8.8 percentage of participants
Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 >=70%	10.7 percentage of participants	1.8 percentage of participants
Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 >=80%	8.9 percentage of participants	1.8 percentage of participants
Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 >=90%	3.6 percentage of participants	1.8 percentage of participants

SECONDARY outcome

Timeframe: Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12

Population: modified intent to treat analysis. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.

This outcome is similar to the primary outcome except that AIMS was read locally. 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. This outcome reports the local reading of AIMS data. This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement. A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point (weeks 2, 4, 6, 9, and 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate.

Outcome measures

Outcome measures
Measure	SD-809 n=52 Participants Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=51 Participants Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Change in Locally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis	-4.9 units on a scale Standard Error 0.64	-3.7 units on a scale Standard Error 0.65

Adverse Events

SD-809

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SD-809 n=58 participants at risk Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=59 participants at risk Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Infections and infestations Pneumonia	1.7% 1/58 • Number of events 1 • Day 1 to Week 12	1.7% 1/59 • Number of events 1 • Day 1 to Week 12
Infections and infestations Abscess jaw	0.00% 0/58 • Day 1 to Week 12	1.7% 1/59 • Number of events 1 • Day 1 to Week 12
Injury, poisoning and procedural complications Overdose	0.00% 0/58 • Day 1 to Week 12	1.7% 1/59 • Number of events 1 • Day 1 to Week 12
Injury, poisoning and procedural complications Jaw fracture	0.00% 0/58 • Day 1 to Week 12	1.7% 1/59 • Number of events 1 • Day 1 to Week 12
Psychiatric disorders Schizophrenia	1.7% 1/58 • Number of events 1 • Day 1 to Week 12	0.00% 0/59 • Day 1 to Week 12
Psychiatric disorders Mania	1.7% 1/58 • Number of events 1 • Day 1 to Week 12	0.00% 0/59 • Day 1 to Week 12
Respiratory, thoracic and mediastinal disorders Laryngeal hypertrophy	0.00% 0/58 • Day 1 to Week 12	1.7% 1/59 • Number of events 1 • Day 1 to Week 12

Other adverse events

Other adverse events
Measure	SD-809 n=58 participants at risk Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.	Placebo n=59 participants at risk Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.
Gastrointestinal disorders Dry mouth	3.4% 2/58 • Number of events 2 • Day 1 to Week 12	10.2% 6/59 • Number of events 6 • Day 1 to Week 12
Gastrointestinal disorders Diarrhoea	5.2% 3/58 • Number of events 3 • Day 1 to Week 12	5.1% 3/59 • Number of events 4 • Day 1 to Week 12
Gastrointestinal disorders Vomiting	1.7% 1/58 • Number of events 1 • Day 1 to Week 12	5.1% 3/59 • Number of events 3 • Day 1 to Week 12
General disorders Fatigue	6.9% 4/58 • Number of events 4 • Day 1 to Week 12	8.5% 5/59 • Number of events 6 • Day 1 to Week 12
Infections and infestations Upper respiratory tract infection	3.4% 2/58 • Number of events 3 • Day 1 to Week 12	5.1% 3/59 • Number of events 3 • Day 1 to Week 12
Nervous system disorders Somnolence	13.8% 8/58 • Number of events 8 • Day 1 to Week 12	10.2% 6/59 • Number of events 8 • Day 1 to Week 12
Nervous system disorders Headache	5.2% 3/58 • Number of events 3 • Day 1 to Week 12	10.2% 6/59 • Number of events 6 • Day 1 to Week 12
Nervous system disorders Dizziness	3.4% 2/58 • Number of events 2 • Day 1 to Week 12	5.1% 3/59 • Number of events 3 • Day 1 to Week 12
Nervous system disorders Akathisia	5.2% 3/58 • Number of events 3 • Day 1 to Week 12	0.00% 0/59 • Day 1 to Week 12
Psychiatric disorders Anxiety	3.4% 2/58 • Number of events 2 • Day 1 to Week 12	6.8% 4/59 • Number of events 4 • Day 1 to Week 12
Psychiatric disorders Insomnia	6.9% 4/58 • Number of events 4 • Day 1 to Week 12	1.7% 1/59 • Number of events 1 • Day 1 to Week 12
Skin and subcutaneous tissue disorders Rash	1.7% 1/58 • Number of events 1 • Day 1 to Week 12	5.1% 3/59 • Number of events 3 • Day 1 to Week 12

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc

Phone: 215-591-3000

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