ARM-TD: Aim to Reduce Movements in Tardive Dyskinesia

• Sponsor: Auspex Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02195700
• Collaborator: (none)
• Enrollment: 117
• Locations: 41
• Arms: 2
• Actual Duration (Months): 11
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether 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 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia
• Actual Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SD-809 SD-809 tablets taken twice daily for 12 weeks.	Drug: SD-809; SD-809 tablets taken twice daily for 12 weeks, includes a dose titration period and maintenance period.; Other Names: deutetrabenazine AUSTEDO®
Placebo Comparator: Sugar Pill Placebo tablets taken twice daily for 12 weeks.	Drug: Placebo; Placebo tablets taken twice daily for 12 weeks.

Outcome Measures

Primary Outcome Measures

1. Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis [Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12]

   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.

Secondary Outcome Measures

1. Percentage of Patients Who Are 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.

2. Percentage of Patients Who Are 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.

3. Change From Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24) [Day 0 (Baseline), Week 12 with last observation carried forward]

   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.

4. Participants With Adverse Events for 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.

5. Percentage Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis [Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12]

   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.

6. Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 [Day 0 (Baseline), Week 12]

   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.

7. Change in Locally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis [Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 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 agree to an acceptable method of contraception

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 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		Tuscaloosa	Alabama	United States
2		Anaheim	California	United States
3		Glendale	California	United States
4		Oceanside	California	United States
5		Orange	California	United States
6		San Bernardino	California	United States
7		San Diego	California	United States
8		Denver	Colorado	United States
9		New Haven	Connecticut	United States
10		Stamford	Connecticut	United States
11		Washington	District of Columbia	United States
12		Boca Raton	Florida	United States
13		Gainesville	Florida	United States
14		Lake City	Florida	United States
15		Miami	Florida	United States
16		Orlando	Florida	United States
17		Port Charlotte	Florida	United States
18		Chicago	Illinois	United States
19		Baltimore	Maryland	United States
20		Minneapolis	Minnesota	United States
21		Kansas City	Missouri	United States
22		Saint Louis	Missouri	United States
23		Albuquerque	New Mexico	United States
24		Asheville	North Carolina	United States
25		Durham	North Carolina	United States
26		Raleigh	North Carolina	United States
27		Cleveland	Ohio	United States
28		Philadelphia	Pennsylvania	United States
29		Charleston	South Carolina	United States
30		Memphis	Tennessee	United States
31		Fort Worth	Texas	United States
32		Salt Lake City	Utah	United States
33		Prague		Czechia
34		Gdansk		Poland
35		Katowice		Poland
36		Krakow		Poland
37		Lodz		Poland
38		Lublin		Poland
39		Torun		Poland
40		Hronovce		Slovakia
41		Roznava		Slovakia

Sponsors and Collaborators

• Auspex Pharmaceuticals, Inc.

Investigators

• Study Director: Teva Medical Expert, M.D., 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: NCT02195700
• Other Study ID Numbers: SD-809-C-18
• First Posted: Jul 21, 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

Pre-assignment Detail	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.

Arm/Group Title	SD-809	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	58	59
Safety and ITT Populations	58	59
Modified ITT Population	56	57
Maintenance Period	53	54
COMPLETED	52	52
NOT COMPLETED	6	7

Baseline Characteristics

Arm/Group Title	SD-809	Placebo	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	58	59	117
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.9 (9.82)	53.3 (10.64)	54.6 (10.28)
Sex: Female, Male (Count of Participants)
Female	29 50%	32 54.2%	61 52.1%
Male	29 50%	27 45.8%	56 47.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 6.9%	11 18.6%	15 12.8%
Not Hispanic or Latino	53 91.4%	47 79.7%	100 85.5%
Unknown or Not Reported	1 1.7%	1 1.7%	2 1.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 3.4%	1 1.7%	3 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	19 32.8%	14 23.7%	33 28.2%
White	37 63.8%	44 74.6%	81 69.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Education Level (Count of Participants)
=12 years or fewer of formal education	30 51.7%	30 50.8%	60 51.3%
>12 years of formal education	28 48.3%	29 49.2%	57 48.7%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	86.94 (24.081)	84.95 (20.975)	85.94 (22.493)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	169.23 (11.462)	169.72 (10.098)	169.48 (10.752)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.35 (7.926)	29.45 (6.958)	29.89 (7.435)
Using a Dopamine Receptor Antagonist (DRA) (Count of Participants)
Yes	45 77.6%	49 83.1%	94 80.3%
No	13 22.4%	10 16.9%	23 19.7%
Duration of tardive dyskinesia (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	72.6 (81.65)	76.8 (82.05)	74.7 (81.53)
Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	9.6 (4.07)	9.6 (3.77)	9.6 (3.90)
Modified Craniocervical Dystonia Questionnaire (CDQ-24) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	38.4 (20.41)	39.7 (18.17)	39.1 (19.26)

Outcome Measures

1. Primary Outcome

Title	Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis
Description	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.
Time Frame	Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	SD-809	Placebo
Arm/Group Description	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.	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.
Measure Participants	52	51
Least Squares Mean (Standard Error) [units on a scale]	-3.0 (0.45)	-1.6 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SD-809, Placebo
	Comments	The linear mixed model for repeated measurements (MMRM) included fixed effects for treatment, each scheduled time point (5 levels: weeks 2, 4, 6, 9, and 12), the treatment-by-time point interaction, and the DRA status. Baseline AIMS score was a covariate. The unstructured covariance model was used, and the primary analysis compared the SD-809 and placebo groups at week 12. This was based on the F-test using the Satterhwaite method to compute the denominator degrees of freedom.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0188
	Comments	5% level of significance (2-sided)
	Method	unstructured covariance
	Comments
Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -2.6 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.60
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Patients Who Are 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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

modified intent to treat population

Arm/Group Title	SD-809	Placebo
Arm/Group Description	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.	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.
Measure Participants	56	57
Number [percentage of participants]	48.2 83.1%	40.4 68.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SD-809, Placebo
	Comments	The secondary efficacy endpoints were analyzed using a hierarchical testing procedure. If the primary analysis was statistically significant (p<0.05), then the first key secondary endpoint was to be analyzed. If the first key secondary endpoint was statistically significant, then the second key secondary endpoint was to be similarly analyzed. For any analysis that was not statistically significant, all subsequent analyses of key secondary endpoints were exploratory rather than confirmatory.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4001
	Comments	5% level of significance (2-sided)
	Method	Pearson's chi-square test
	Comments
Method of Estimation	Estimation Parameter	Differences in %
	Estimated Value	7.9
	Confidence Interval	(2-Sided) 95%; -10.2 to 25.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Patients Who Are 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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

modified intent to treat population

Arm/Group Title	SD-809	Placebo
Arm/Group Description	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.	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.
Measure Participants	56	57
Number [percentage of participants]	42.9 74%	29.8 50.5%

4. Secondary Outcome

Title	Change From Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24)
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 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.
Time Frame	Day 0 (Baseline), Week 12 with last observation carried forward

Outcome Measure Data

Analysis Population Description

modified intent to treat population

Arm/Group Title	SD-809	Placebo
Arm/Group Description	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.	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.
Measure Participants	56	57
Least Squares Mean (Standard Error) [units on a scale]	-11.1 (2.14)	-8.3 (2.31)

5. Secondary Outcome

Title	Participants With Adverse Events for 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

Safety population

Arm/Group Title	SD-809	Placebo
Arm/Group Description	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.	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.
Measure Participants	58	59
Overall Treatment Period: any AE	41 70.7%	36 61%
Overall Treatment Period: SAE	3 5.2%	5 8.5%
Overall Treatment Period: Severe AE	3 5.2%	3 5.1%
Overall Treatment Period: treatment-related AE	28 48.3%	21 35.6%
Overall Treatment Period: Deaths	0 0%	0 0%

6. Secondary Outcome

Title	Percentage Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis
Description	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.
Time Frame	Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SD-809	Placebo
Arm/Group Description	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.	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.
Measure Participants	52	51
Least Squares Mean (Standard Error) [percentage change]	-26.7 (6.06)	-15.5 (6.26)

7. Secondary Outcome

Title	Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12
Description	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.
Time Frame	Day 0 (Baseline), Week 12

Outcome Measure Data

Analysis Population Description

modified intent to treat population.

Arm/Group Title	SD-809	Placebo
Arm/Group Description	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.	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.
Measure Participants	56	57
>=10%	69.6 120%	42.1 71.4%
>=20%	50.0 86.2%	29.8 50.5%
>=30%	46.4 80%	24.6 41.7%
>=40%	32.1 55.3%	22.8 38.6%
>=50%	23.2 40%	17.5 29.7%
>=60%	19.6 33.8%	8.8 14.9%
>=70%	10.7 18.4%	1.8 3.1%
>=80%	8.9 15.3%	1.8 3.1%
>=90%	3.6 6.2%	1.8 3.1%

8. Secondary Outcome

Title	Change in Locally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis
Description	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.
Time Frame	Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SD-809	Placebo
Arm/Group Description	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.	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.
Measure Participants	52	51
Least Squares Mean (Standard Error) [units on a scale]	-4.9 (0.64)	-3.7 (0.65)

Adverse Events

Time Frame	Day 1 to Week 12
Arm/Group Title	SD-809		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	SD-809		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/59 (0%)
Serious Adverse Events
	SD-809		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/58 (5.2%)		5/59 (8.5%)
Infections and infestations
Pneumonia	1/58 (1.7%)	1	1/59 (1.7%)	1
Abscess jaw	0/58 (0%)	0	1/59 (1.7%)	1
Injury, poisoning and procedural complications
Overdose	0/58 (0%)	0	1/59 (1.7%)	1
Jaw fracture	0/58 (0%)	0	1/59 (1.7%)	1
Psychiatric disorders
Schizophrenia	1/58 (1.7%)	1	0/59 (0%)	0
Mania	1/58 (1.7%)	1	0/59 (0%)	0
Respiratory, thoracic and mediastinal disorders
Laryngeal hypertrophy	0/58 (0%)	0	1/59 (1.7%)	1
Other (Not Including Serious) Adverse Events
	SD-809		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/58 (41.4%)		26/59 (44.1%)
Gastrointestinal disorders
Dry mouth	2/58 (3.4%)	2	6/59 (10.2%)	6
Diarrhoea	3/58 (5.2%)	3	3/59 (5.1%)	4
Vomiting	1/58 (1.7%)	1	3/59 (5.1%)	3
General disorders
Fatigue	4/58 (6.9%)	4	5/59 (8.5%)	6
Infections and infestations
Upper respiratory tract infection	2/58 (3.4%)	3	3/59 (5.1%)	3
Nervous system disorders
Somnolence	8/58 (13.8%)	8	6/59 (10.2%)	8
Headache	3/58 (5.2%)	3	6/59 (10.2%)	6
Dizziness	2/58 (3.4%)	2	3/59 (5.1%)	3
Akathisia	3/58 (5.2%)	3	0/59 (0%)	0
Psychiatric disorders
Anxiety	2/58 (3.4%)	2	4/59 (6.8%)	4
Insomnia	4/58 (6.9%)	4	1/59 (1.7%)	1
Skin and subcutaneous tissue disorders
Rash	1/58 (1.7%)	1	3/59 (5.1%)	3

Limitations/Caveats

[Not Specified]

More Information

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.