AIM-TD: Addressing Involuntary Movements in Tardive Dyskinesia

• Sponsor: Auspex Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02291861
• Collaborator: (none)
• Enrollment: 298
• Locations: 106
• Arms: 4
• Actual Duration (Months): 21.6
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether fixed-doses of an investigational drug, SD-809 (deutetrabenazine), will reduce the severity of abnormal involuntary movements of tardive dyskinesia.

Condition or Disease	Intervention/Treatment	Phase
Tardive Dyskinesia	Drug: SD-809; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 298 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia
• Actual Study Start Date: Oct 31, 2014
• Actual Primary Completion Date: Aug 19, 2016
• Actual Study Completion Date: Aug 19, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo tablets taken twice daily for 12 weeks.	Drug: Placebo; Placebo tablets taken twice daily for 12 weeks. Tablets were swallowed whole with water and taken with food.
Experimental: SD-809 12 mg/day SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	Drug: SD-809; SD-809 tablets dose titrated for 4 weeks until target randomized dose is reached. The dose is maintained for an additional 8 weeks. Tablets were swallowed whole with water and taken with food.; Other Names: deutetrabenzine Austedo
Experimental: SD-809 24 mg/day SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	Drug: SD-809; SD-809 tablets dose titrated for 4 weeks until target randomized dose is reached. The dose is maintained for an additional 8 weeks. Tablets were swallowed whole with water and taken with food.; Other Names: deutetrabenzine Austedo
Experimental: SD-809 36 mg/day SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.	Drug: SD-809; SD-809 tablets dose titrated for 4 weeks until target randomized dose is reached. The dose is maintained for an additional 8 weeks. Tablets were swallowed whole with water and taken with food.; Other Names: deutetrabenzine Austedo

Outcome Measures

Primary Outcome Measures

1. Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model For Repeated Measures (MMRM) [Day 0 (Baseline), Weeks 2, 4, 8 and 12]

   AIMS is an assessment tool used to detect and follow the severity of tardive dyskinesia (TD) over time. AIMS is composed of 12 clinician-administered and scored items. The exam 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, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. MMRM with treatment group, visit, treatment group-by-visit interaction, and baseline use of dopamine receptor antagonist (DRAs) as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.

Secondary Outcome Measures

1. Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC) [Week 12]

   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. The success 95% confidence interval (CI) was calculated with the Wilson (score) confidence limits.

2. Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score From Baseline to Week 12 [Day 0 (Baseline), Week 12]

   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 mCDQ-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 - 96. Negative change from baseline scores indicate improvement. For patients with missing data at week 12, the baseline or last available value was used as the week 12 value.

3. Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC) [Week 12]

   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. The success 95% CI was calculated with the Wilson (score) confidence limits.

4. Percentage of Participants Who Had a 50% or Greater Reduction in Total Motor Abnormal Involuntary Movement Scale (AIMS) From Baseline to Week 12 [Day 0 (Baseline), Week 12]

   Responders who had a 50% or greater improvement in total motor modified AIMS at Week 12 as compared to baseline were reported as a percentage of participants with an outcome at Week 12. The responder 95% CI is calculated with the Wilson (score) confidence limits. AIMS is an assessment tool used to detect and follow the severity of TD over time. AIMS is composed of 12 clinician-administered and scored items. The exam 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, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement.

5. Percent Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model for Repeated Measures (MMRM) [Day 0 (Baseline), Weeks 2, 4, 8 and 12]

   AIMS is an assessment tool used to detect and follow the severity of TD over time. AIMS is composed of 12 clinician-administered and scored items. The exam 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, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. MMRM with treatment group, visit, treatment group-by-visit interaction, and baseline use of DRAs as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.

6. Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points [Day 0 (Baseline), Week 12]

   AIMS is an assessment tool used to detect and follow the severity of TD over time, composed of 12 clinician-administered and scored items. The exam 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, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. Participants with missing data are classified as non-responders. The responder 95% CI is calculated with the Wilson (score) confidence limits. If any of the expected cell counts are < 5, exact Clopper Pearson limits are presented. Data report the percentage of participants who responded to the percentage improvement indicated in each row.

7. Participants With Adverse Events During the Overall Treatment Period [Day 1 to Week 12]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• History of using a dopamine receptor antagonist for at least 3 months

• Clinical diagnosis of tardive dyskinesia and has had symptoms for at least 3 months prior to screening

• Subjects with underlying psychiatric diagnosis are stable and have no change in psychoactive medications

• Have a mental health provider and does not anticipate any changes to treatment regimen in the next 3 months

• History of being compliant with prescribed medications

• Able to swallow study drug whole

• Be in good general health and is expected to attend all study visits and complete study assessments

• Female subjects must not be pregnant and must agree to an acceptable method of contraception throughout the study

Exclusion Criteria:

• Currently receiving medication for the treatment of tardive dyskinesia

• Have a neurological condition other than tardive dyskinesia that may interfere with assessing the severity of dyskinesias

• Have a serious untreated or undertreated psychiatric illness

• Have recent history or presence of violent behavior

• Have unstable or serious medical illness

• Have evidence of hepatic impairment

• Have evidence of renal impairment

• Have known allergy to any component of SD-809 or tetrabenazine

• Has participated in an investigational drug or device trial and received study drug or device within 30 days

• Have acknowledged use of illicit drugs

• Have a history of alcohol or substance abuse in the previous 12 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 145	Tuscaloosa	Alabama	United States	35404
2	Teva Investigational Site 107	Anaheim	California	United States	92804
3	Teva Investigational Site 108	Anaheim	California	United States	92805
4	Teva Investigational Site 123	Glendale	California	United States	91206
5	Teva Investigational Site 177	Imperial	California	United States	92251
6	Teva Investigational Site 160	Irvine	California	United States	92614
7	Teva Investigational Site 106	Irvine	California	United States	92697
8	Teva Investigational Site 176	Loma Linda	California	United States	92354
9	Teva Investigational Site 121	Los Angeles	California	United States	90033
10	Teva Investigational Site 147	Los Angeles	California	United States	90095-1769
11	Teva Investigational Site 174	Norwalk	California	United States	90650
12	Teva Investigational Site 170	Oceanside	California	United States	92056
13	Teva Investigational Site 102	Orange	California	United States	92868
14	Teva Investigational Site 104	San Bernardino	California	United States	92408
15	Teva Investigational Site 110	San Diego	California	United States	92108
16	Teva Investigational Site 169	San Rafael	California	United States	94901
17	Teva Investigational Site 129	Englewood	Colorado	United States	80113
18	Teva Investigational Site 139	New Haven	Connecticut	United States	06519
19	Teva Investigational Site 156	Washington	District of Columbia	United States	20007
20	Teva Investigational Site 157	Boca Raton	Florida	United States	33486
21	Teva Investigational Site 117	Gainesville	Florida	United States	32607
22	Teva Investigational Site 150	Lake City	Florida	United States	32025
23	Teva Investigational Site 153	Miami	Florida	United States	33135
24	Teva Investigational Site 162	Miami	Florida	United States	33165
25	Teva Investigational Site 112	Orlando	Florida	United States	32803
26	Teva Investigational Site 144	Port Charlotte	Florida	United States	33980
27	Teva Investigational Site 155	Augusta	Georgia	United States	30912
28	Teva Investigational Site 165	Decatur	Georgia	United States	30033
29	Teva Investigational Site 131	Chicago	Illinois	United States	60611
30	Teva Investigational Site 113	Chicago	Illinois	United States	60612
31	Teva Investigational Site 164	Kansas City	Kansas	United States	66160
32	Teva Investigational Site 154	Baltimore	Maryland	United States	21287
33	Teva Investigational Site 101	Glen Burnie	Maryland	United States	21061
34	Teva Investigational Site 135	Boston	Massachusetts	United States	02215
35	Teva Investigational Site 118	Creve Coeur	Missouri	United States	63141
36	Teva Investigational Site 142	Kansas City	Missouri	United States	64108
37	Teva Investigational Site 175	Saint Louis	Missouri	United States	63104
38	Teva Investigational Site 161	Saint Louis	Missouri	United States	63109
39	Teva Investigational Site 178	Lincoln	Nebraska	United States	68526-9467
40	Teva Investigational Site 128	Albuquerque	New Mexico	United States	87106
41	Teva Investigational Site 172	Commack	New York	United States	11725
42	Teva Investigational Site 148	New York	New York	United States	10032
43	Teva Investigational Site 138	Asheville	North Carolina	United States	28805
44	Teva Investigational Site 146	Raleigh	North Carolina	United States
45	Teva Investigational Site 133	Charleston	South Carolina	United States	29425
46	Teva Investigational Site 149	Memphis	Tennessee	United States	38163
47	Teva Investigational Site 151	Fort Worth	Texas	United States	76104
48	Teva Investigational Site 115	Salt Lake City	Utah	United States	84105
49	Teva Investigational Site 141	Salt Lake City	Utah	United States	84108
50	Teva Investigational Site 168	Burlington	Vermont	United States	05401
51	Teva Investigational Site 171	Charlottesville	Virginia	United States	22903
52	Teva Investigational Site 167	Richland	Washington	United States	99352
53	Teva Investigational Site 166	Waukesha	Wisconsin	United States	53188
54	Teva Investigational Site 559	Havirov		Czechia	736 01
55	Teva Investigational Site 556	Hostivice		Czechia
56	Teva Investigational Site 558	Hradec Kralove		Czechia	503 41
57	Teva Investigational Site 535	Litomerice		Czechia	412 01
58	Teva Investigational Site 557	Plzen		Czechia	312 00
59	Teva Investigational Site 530	Prague 6		Czechia	16000
60	Teva Investigational Site 531	Prague 8		Czechia	181 02
61	Teva Investigational Site 533	Praha 10		Czechia	100 00
62	Teva Investigational Site 532	Praha 5		Czechia	158 00
63	Teva Investigational Site 534	Praha 9		Czechia	190 00
64	Teva Investigational Site 502	Gera		Germany	07551
65	Teva Investigational Site 503	Haag In Oberbayern		Germany	83527
66	Teva Investigational Site 504	Mainz		Germany	55131
67	Teva Investigational Site 507	Prien am Chiemsee		Germany	83209
68	Teva Investigational Site 544	Taufkirchen		Germany	84416
69	Teva Investigational Site 501	Wolfach		Germany	77709
70	Teva Investigational Site 540	Balassagyarmat		Hungary
71	Teva Investigational Site 538	Budapest		Hungary	1135
72	Teva Investigational Site 541	Budapest		Hungary	1148
73	Teva Investigational Site 537	Budapest		Hungary	1204
74	Teva Investigational Site 542	Budapest		Hungary	H-1135
75	Teva Investigational Site 539	Doba		Hungary	8482
76	Teva Investigational Site 546	Gyor		Hungary	9024
77	Teva Investigational Site 545	Kalocsa		Hungary	6300
78	Teva Investigational Site 547	Szeged		Hungary	6725
79	Teva Investigational Site 514	Belchatow		Poland	97-400
80	Teva Investigational Site 554	Bialystok		Poland	15-756
81	Teva Investigational Site 510	Bydgoszcz		Poland	85-015
82	Teva Investigational Site 519	Bydgoszcz		Poland	85-080
83	Teva Investigational Site 536	Bydgoszcz		Poland	85-156
84	Teva Investigational Site 523	Chelmno		Poland	86-200
85	Teva Investigational Site 517	Choroszcz		Poland	16-070
86	Teva Investigational Site 513	Gdansk		Poland	80-952
87	Teva Investigational Site 512	Katowice		Poland	40-097
88	Teva Investigational Site 552	Katowice		Poland	40-123
89	Teva Investigational Site 520	Krakow		Poland	30-349
90	Teva Investigational Site 509	Krakow		Poland	31-505
91	Teva Investigational Site 508	Lodz		Poland	90-130
92	Teva Investigational Site 511	Lublin		Poland	20-064
93	Teva Investigational Site 515	Lublin		Poland	20-090
94	Teva Investigational Site 524	Lublin		Poland	20-831
95	Teva Investigational Site 549	Olsztyn		Poland	10-443
96	Teva Investigational Site 521	Pruszkow		Poland	05-802
97	Teva Investigational Site 518	Sosnowiec		Poland	41-200
98	Teva Investigational Site 522	Torun		Poland	87-100
99	Teva Investigational Site 550	Warszawa		Poland	00-465
100	Teva Investigational Site 555	Warszawa		Poland	00-669
101	Teva Investigational Site 516	Wroclaw		Poland	50-227
102	Teva Investigational Site 529	Bratislava		Slovakia	826 06
103	Teva Investigational Site 525	Hronovce		Slovakia	935 61
104	Teva Investigational Site 527	Kosice		Slovakia	04017
105	Teva Investigational Site 528	Rimavska Sobota		Slovakia	979 12
106	Teva Investigational Site 526	Roznava		Slovakia	04801

Sponsors and Collaborators

• Auspex Pharmaceuticals, Inc.

Investigators

• Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Auspex Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02291861
• Other Study ID Numbers: SD-809-C-23; 2014-003135-19
• First Posted: Nov 17, 2014
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Auspex Pharmaceuticals, Inc.: Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms
• Additional relevant MeSH terms: Dyskinesias; Tardive Dyskinesia

Study Results

Participant Flow

Recruitment Details	This study was performed at 75 study centers (38 in the US, 19 in Poland, 7 in Hungary, 6 in the Czech Republic, 3 in Slovakia, and 2 in Germany) by 75 investigators; 298 patients were enrolled.
Pre-assignment Detail	Participants were randomly assigned in a 1:1:1:1 ratio to receive 1 of 3 fixed-dose regimens of SD-809 (deutetrabenazine) or placebo following a screening period.

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
Period Title: Overall Study
STARTED	74	75	74	75
Safety Population	72	74	73	74
Modified Intent to Treat Pop (mITT)	58	60	49	55
COMPLETED	67	67	65	65
NOT COMPLETED	7	8	9	10

Baseline Characteristics

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day	Total
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.	Total of all reporting groups
Overall Participants	72	74	73	74	293
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (12.06)	57.0 (9.95)	55.6 (11.34)	58.3 (11.55)	56.4 (11.27)
Sex: Female, Male (Count of Participants)
Female	37 51.4%	42 56.8%	41 56.2%	42 56.8%	162 55.3%
Male	35 48.6%	32 43.2%	32 43.8%	32 43.2%	131 44.7%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 1.4%	1 1.4%	0 0%	2 2.7%	4 1.4%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	12 16.7%	15 20.3%	19 26%	10 13.5%	56 19.1%
Native Hawaiian or Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
White	59 81.9%	58 78.4%	54 74%	61 82.4%	232 79.2%
Other	0 0%	0 0%	0 0%	1 1.4%	1 0.3%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or latino	7 9.7%	6 8.1%	3 4.1%	7 9.5%	23 7.8%
Not hispanic or latino	64 88.9%	64 86.5%	69 94.5%	65 87.8%	262 89.4%
Not reported	0 0%	3 4.1%	1 1.4%	1 1.4%	5 1.7%
Unknown	1 1.4%	1 1.4%	0 0%	1 1.4%	3 1%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	82.8 (18.51)	80.8 (21.00)	86.8 (18.79)	78.5 (17.56)	82.2 (19.16)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	168.3 (9.25)	167.7 (10.68)	168.7 (9.39)	167.6 (10.55)	168.1 (9.96)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.18 (6.128)	28.69 (6.814)	30.64 (7.021)	27.99 (6.178)	29.12 (6.587)
Education Level (Count of Participants)
<= 12 years	40 55.6%	44 59.5%	44 60.3%	39 52.7%	167 57%
> 12 years	32 44.4%	30 40.5%	29 39.7%	35 47.3%	126 43%
Time Since Tardive Dyskinesia (TD) Diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.03 (5.353)	5.49 (5.426)	4.98 (6.034)	5.89 (5.342)	5.60 (5.532)
Total Motor Abnormal Involuntary Movement Scale (AIMS) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	8.5 (3.28)	8.6 (3.13)	7.7 (3.51)	8.6 (3.84)	8.4 (3.46)
Modified Craniocervical Dystonia Questionnaire (mCDQ-24) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	40.5 (19.88)	37.2 (20.15)	34.4 (19.59)	34.9 (18.34)	36.7 (19.55)
Baseline Use of a Dopamine Receptor Antagonist (DRA) (Count of Participants)
Yes	56 77.8%	56 75.7%	57 78.1%	53 71.6%	222 75.8%
No	16 22.2%	18 24.3%	16 21.9%	21 28.4%	71 24.2%

Outcome Measures

1. Primary Outcome

Title	Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model For Repeated Measures (MMRM)
Description	AIMS is an assessment tool used to detect and follow the severity of tardive dyskinesia (TD) over time. AIMS is composed of 12 clinician-administered and scored items. The exam 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, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. MMRM with treatment group, visit, treatment group-by-visit interaction, and baseline use of dopamine receptor antagonist (DRAs) as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
Time Frame	Day 0 (Baseline), Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment. For this outcome, participants with baseline readings and during-study readings through Week 12 are included.

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
Measure Participants	56	53	45	52
Least Squares Mean (Standard Error) [units on a scale]	-1.4 (0.41)	-2.1 (0.42)	-3.2 (0.45)	-3.3 (0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 36 mg/Day
	Comments	A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. The primary endpoint compared the change in total motor AIMS score from baseline to week 12 between the SD-809 36 mg/day group and the placebo group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Treatment group, visit, treatment group-by-visit interaction, and baseline use of DRAs as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -3.09 to -0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809 - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 24 mg/Day
	Comments	A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the change in total motor AIMS score from baseline to week 12 between the SD-809 24 mg/day group and the placebo group, and is the third analysis in the fixed-sequence.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Treatment group, visit, treatment group-by-visit interaction, and baseline use of DRAs as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -3.00 to -0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809 - placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 12 mg/Day
	Comments	A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the change in total motor AIMS score from baseline to week 12 between the SD-809 12 mg/day group and the placebo group, and is the fifth analysis in the fixed-sequence.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.217
	Comments	Treatment group, visit, treatment group-by-visit interaction, and baseline use of DRAs as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.84 to 0.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809 - placebo

2. Secondary Outcome

Title	Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)
Description	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. The success 95% confidence interval (CI) was calculated with the Wilson (score) confidence limits.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment.

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
Measure Participants	58	60	49	55
Number (95% Confidence Interval) [percentage of participants]	26 36.1%	28 37.8%	49 67.1%	44 59.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 36 mg/Day
	Comments	A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the percentage of patients considered a treatment success at week 12 between the SD-809 36 mg/day group and the placebo group, and is the second analysis in the fixed-sequence.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	The statistical test was a Cochran-Mantel-Haenszel (CMH) test stratified by baseline use of dopamine receptor antagonist (DRAs).
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.11
	Confidence Interval	(2-Sided) 95%; 0.960 to 4.645
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809/placebo The odds ratio was the Mantel-Haenszel estimate of the common odds ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 24 mg/Day
	Comments	A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the percentage of patients considered a treatment success at week 12 between the SD-809 24 mg/day group and the placebo group, and is the fourth analysis in the fixed-sequence.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	The statistical test was a CMH test stratified by baseline use of DRAs.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.71
	Confidence Interval	(2-Sided) 95%; 1.211 to 6.052
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809/placebo The odds ratio was the Mantel-Haenszel estimate of the common odds ratio.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 12 mg/Day
	Comments	A hierarchical (fixed-sequence) testing approach was used for the analysis of the primary and key secondary endpoints to maintain the experiment-wise type I error rate of 5%. This key secondary endpoint compared the percentage of patients considered a treatment success at week 12 between the SD-809 12 mg/day group and the placebo group, and is the sixth (last) analysis in the fixed-sequence.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.734
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	The statistical test was a CMH test stratified by baseline use of DRAs.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.509 to 2.610
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809/placebo The odds ratio was the Mantel-Haenszel estimate of the common odds ratio.

3. Secondary Outcome

Title	Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score From Baseline to Week 12
Description	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 mCDQ-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 - 96. Negative change from baseline scores indicate improvement. For patients with missing data at week 12, the baseline or last available value was used as the week 12 value.
Time Frame	Day 0 (Baseline), Week 12

Outcome Measure Data

Analysis Population Description

The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment. One SD-809 12 mg/day participant was missing a baseline mCDQ-24.

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
Measure Participants	58	59	49	55
Least Squares Mean (Standard Error) [units on a scale]	-7.1 (2.06)	-5.8 (2.03)	-10.2 (2.21)	-10.7 (2.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 36 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.207
	Comments	5% level of significance (2-sided)
	Method	ANCOVA
	Comments	The statistical model was an ANCOVA with treatment group and baseline use of DRAs as fixed effects and the baseline value as a covariate.
Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-3.6
	Confidence Interval	(2-Sided) 95%; -9.18 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809 - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 24 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.281
	Comments	5% level of significance (2-sided)
	Method	ANCOVA
	Comments	The statistical model was an ANCOVA with treatment group and baseline use of DRAs as fixed effects and the baseline value as a covariate.
Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 95%; -8.86 to 2.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809 - placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 12 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.627
	Comments	5% level of significance (2-sided)
	Method	ANCOVA
	Comments	The statistical model was an ANCOVA with treatment group and baseline use of DRAs as fixed effects and the baseline value as a covariate.
Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -4.10 to 6.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809 - placebo

4. Secondary Outcome

Title	Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)
Description	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. The success 95% CI was calculated with the Wilson (score) confidence limits.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
Measure Participants	58	60	49	55
Number (95% Confidence Interval) [percentage of participants]	31 43.1%	23 31.1%	45 61.6%	40 54.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 36 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.296
	Comments	5% level of significance (2-sided)
	Method	Cochran-Mantel-Haenszel
	Comments	The statistical test was a CMH test stratified by baseline use of DRAs.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95%; 0.694 to 3.285
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809/placebo The odds ratio was the Mantel-Haenszel estimate of the common odds ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 24 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.134
	Comments	5% level of significance (2-sided)
	Method	Cochran-Mantel-Haenszel
	Comments	The statistical test was a CMH test stratified by baseline use of DRAs.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.82
	Confidence Interval	(2-Sided) 95%; 0.826 to 3.994
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809/placebo The odds ratio was the Mantel-Haenszel estimate of the common odds ratio.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 12 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.372
	Comments	5% level of significance (2-sided)
	Method	Cochran-Mantel-Haenszel
	Comments	The statistical test was a CMH test stratified by baseline use of DRAs.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.302 to 1.563
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809/placebo The odds ratio was the Mantel-Haenszel estimate of the common odds ratio.

5. Secondary Outcome

Title	Percentage of Participants Who Had a 50% or Greater Reduction in Total Motor Abnormal Involuntary Movement Scale (AIMS) From Baseline to Week 12
Description	Responders who had a 50% or greater improvement in total motor modified AIMS at Week 12 as compared to baseline were reported as a percentage of participants with an outcome at Week 12. The responder 95% CI is calculated with the Wilson (score) confidence limits. AIMS is an assessment tool used to detect and follow the severity of TD over time. AIMS is composed of 12 clinician-administered and scored items. The exam 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, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement.
Time Frame	Day 0 (Baseline), Week 12

Outcome Measure Data

Analysis Population Description

mITT population of participants. Participants with missing Week 12 data were considered non-responders.

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
Measure Participants	58	60	49	55
Number (95% Confidence Interval) [percentage of participants]	12 16.7%	13 17.6%	35 47.9%	33 44.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 36 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments	5% level of significance (2-sided)
	Method	Cochran-Mantel-Haenszel
	Comments	The statistical test was a CMH test stratified by baseline use of DRAs.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.80
	Confidence Interval	(2-Sided) 95%; 1.395 to 10.359
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809/placebo The odds ratio was the Mantel-Haenszel estimate of the common odds ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 24 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	5% level of significance (2-sided)
	Method	Cochran-Mantel-Haenszel
	Comments	The statistical test was a CMH test stratified by baseline use of DRAs.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.96
	Confidence Interval	(2-Sided) 95%; 1.460 to 10.716
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809/placebo The odds ratio was the Mantel-Haenszel estimate of the common odds ratio.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 12 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.829
	Comments	5% level of significance (2-sided)
	Method	Cochran-Mantel-Haenszel
	Comments	The statistical test was a CMH test stratified by baseline use of DRAs.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.383 to 3.316
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809/placebo The odds ratio was the Mantel-Haenszel estimate of the common odds ratio.

6. Secondary Outcome

Title	Percent Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model for Repeated Measures (MMRM)
Description	AIMS is an assessment tool used to detect and follow the severity of TD over time. AIMS is composed of 12 clinician-administered and scored items. The exam 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, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. MMRM with treatment group, visit, treatment group-by-visit interaction, and baseline use of DRAs as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
Time Frame	Day 0 (Baseline), Weeks 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment. For this outcome, participants with baseline readings and during-study readings through Week 12 are included.

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
Measure Participants	56	53	45	52
Least Squares Mean (Standard Error) [percentage of baseline]	-11.6 (4.32)	-20.0 (4.34)	-31.9 (4.73)	-33.1 (4.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 36 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	5% level of significance (2-sided). Treatment group, visit, treatment group-by-visit interaction, and baseline use of DRAs as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-21.5
	Confidence Interval	(2-Sided) 95%; -33.44 to -9.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809 - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 24 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	5% level of significance (2-sided). Treatment group, visit, treatment group-by-visit interaction, and baseline use of DRAs as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-20.2
	Confidence Interval	(2-Sided) 95%; -32.57 to -7.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809 - placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SD-809 12 mg/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.160
	Comments	5% level of significance (2-sided). Treatment group, visit, treatment group-by-visit interaction, and baseline use of DRAs as fixed effects and the baseline value as a covariate. The model was fit using an unstructured covariance structure.
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.4
	Confidence Interval	(2-Sided) 95%; -20.15 to 3.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	SD-809 - placebo

7. Secondary Outcome

Title	Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
Description	AIMS is an assessment tool used to detect and follow the severity of TD over time, composed of 12 clinician-administered and scored items. The exam 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, as well as extremity and truncal dyskinesia (the total motor AIMS score). Ratings were based on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe) for a total scale of 0-28. A negative change from baseline score indicates improvement. Participants with missing data are classified as non-responders. The responder 95% CI is calculated with the Wilson (score) confidence limits. If any of the expected cell counts are < 5, exact Clopper Pearson limits are presented. Data report the percentage of participants who responded to the percentage improvement indicated in each row.
Time Frame	Day 0 (Baseline), Week 12

Outcome Measure Data

Analysis Population Description

The mITT Population (N=222) included all patients in the ITT Population with a baseline AIMS score ≥6 as assessed by central video rating, were randomized to treatment, received study drug, and had at least 1 postbaseline AIMS assessment.

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
Measure Participants	58	60	49	55
10% Improvement	50 69.4%	62 83.8%	67 91.8%	71 95.9%
20% Improvement	40 55.6%	47 63.5%	59 80.8%	60 81.1%
30% Improvement	31 43.1%	32 43.2%	49 67.1%	49 66.2%
40% Improvement	16 22.2%	23 31.1%	45 61.6%	40 54.1%
50% Improvement	12 16.7%	13 17.6%	35 47.9%	33 44.6%
60% Improvement	5 6.9%	7 9.5%	20 27.4%	18 24.3%
70% Improvement	2 2.8%	3 4.1%	12 16.4%	16 21.6%
80% Improvement	2 2.8%	2 2.7%	2 2.7%	13 17.6%
90% Improvement	2 2.8%	0 0%	0 0%	5 6.8%

8. Secondary Outcome

Title	Participants With Adverse Events During the Overall Treatment Period
Description	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.
Time Frame	Day 1 to Week 12

Outcome Measure Data

Analysis Population Description

The Safety Population was a subset of randomized participants and included all patients who were administered study drug (N=293).

Arm/Group Title	Placebo	SD-809 12 mg/Day	SD-809 24 mg/Day	SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.	SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
Measure Participants	72	74	73	74
Overall Treatment Period: any AE	34 47.2%	36 48.6%	32 43.8%	38 51.4%
Overall Treatment Period: SAE	4 5.6%	2 2.7%	6 8.2%	4 5.4%
Overall Treatment Period: Severe AE	2 2.8%	2 2.7%	4 5.5%	1 1.4%
Overall Treatment Period: treatment-related AE	19 26.4%	13 17.6%	11 15.1%	18 24.3%
Dose reduction because of AE	0 0%	0 0%	1 1.4%	3 4.1%
Dose suspension because of AE	2 2.8%	3 4.1%	1 1.4%	1 1.4%
Withdrawn from study because of AE	2 2.8%	4 5.4%	2 2.7%	3 4.1%

Adverse Events

Time Frame	Day 1 to Week 12
Arm/Group Title	Placebo		SD-809 12 mg/Day		SD-809 24 mg/Day		SD-809 36 mg/Day
Arm/Group Description	Placebo tablets taken twice daily for 12 weeks.		SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.		SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 12 mg BID. The total daily dose of 24 mg was maintained for an additional 8 weeks.		SD-809 tablets dose starting at 6 mg twice a day (BID) and titrated over 4 weeks to 18 mg BID. The total daily dose of 36 mg was maintained for an additional 8 weeks.
All Cause Mortality
	Placebo		SD-809 12 mg/Day		SD-809 24 mg/Day		SD-809 36 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/72 (0%)		0/74 (0%)		1/73 (1.4%)		1/74 (1.4%)
Serious Adverse Events
	Placebo		SD-809 12 mg/Day		SD-809 24 mg/Day		SD-809 36 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/72 (5.6%)		2/74 (2.7%)		6/73 (8.2%)		4/74 (5.4%)
Cardiac disorders
Cardio-respiratory arrest	0/72 (0%)	0	0/74 (0%)	0	0/73 (0%)	0	1/74 (1.4%)	1
Gastrointestinal disorders
Abdominal pain	1/72 (1.4%)	1	0/74 (0%)	0	0/73 (0%)	0	0/74 (0%)	0
Pancreatic mass	1/72 (1.4%)	1	0/74 (0%)	0	0/73 (0%)	0	0/74 (0%)	0
General disorders
Alcohol interaction	0/72 (0%)	0	0/74 (0%)	0	0/73 (0%)	0	1/74 (1.4%)	1
Sudden cardiac death	0/72 (0%)	0	0/74 (0%)	0	1/73 (1.4%)	1	0/74 (0%)	0
Infections and infestations
Appendicitis	0/72 (0%)	0	0/74 (0%)	0	1/73 (1.4%)	1	0/74 (0%)	0
Cellulitis	0/72 (0%)	0	0/74 (0%)	0	1/73 (1.4%)	1	0/74 (0%)	0
Pneumonia	0/72 (0%)	0	0/74 (0%)	0	1/73 (1.4%)	1	1/74 (1.4%)	1
Injury, poisoning and procedural complications
Face injury	0/72 (0%)	0	1/74 (1.4%)	1	0/73 (0%)	0	0/74 (0%)	0
Head injury	1/72 (1.4%)	1	0/74 (0%)	0	0/73 (0%)	0	0/74 (0%)	0
Skeletal injury	0/72 (0%)	0	1/74 (1.4%)	1	0/73 (0%)	0	0/74 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma metastatic	1/72 (1.4%)	1	0/74 (0%)	0	0/73 (0%)	0	0/74 (0%)	0
Nervous system disorders
Psychomotor hyperactivity	0/72 (0%)	0	0/74 (0%)	0	0/73 (0%)	0	1/74 (1.4%)	1
Psychiatric disorders
Bipolar disorder	1/72 (1.4%)	1	0/74 (0%)	0	0/73 (0%)	0	0/74 (0%)	0
Depression	0/72 (0%)	0	0/74 (0%)	0	1/73 (1.4%)	1	0/74 (0%)	0
Psychotic disorder	0/72 (0%)	0	1/74 (1.4%)	1	0/73 (0%)	0	0/74 (0%)	0
Suicidal ideation	0/72 (0%)	0	0/74 (0%)	0	1/73 (1.4%)	1	0/74 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		SD-809 12 mg/Day		SD-809 24 mg/Day		SD-809 36 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/72 (19.4%)		9/74 (12.2%)		9/73 (12.3%)		10/74 (13.5%)
Gastrointestinal disorders
Diarrhoea	2/72 (2.8%)	2	1/74 (1.4%)	1	3/73 (4.1%)	4	5/74 (6.8%)	6
Nausea	7/72 (9.7%)	8	1/74 (1.4%)	1	1/73 (1.4%)	1	1/74 (1.4%)	1
Infections and infestations
Nasopharyngitis	1/72 (1.4%)	1	4/74 (5.4%)	4	3/73 (4.1%)	3	2/74 (2.7%)	2
Nervous system disorders
Headache	4/72 (5.6%)	4	5/74 (6.8%)	7	2/73 (2.7%)	3	5/74 (6.8%)	5

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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