Reducing Involuntary Movements in Participants With Tardive Dyskinesia

Phase 3

Completed

Conditions: Tardive Dyskinesia

Interventions: Drug: SD-809
Drug: Placebo

Registration Number: NCT02198794

Lead Sponsor: Auspex Pharmaceuticals, Inc.

Brief Summary: The purpose of this study is to evaluate the long-term safety, tolerability, and efficacy of SD-809 in reducing the severity of abnormal involuntary movements of moderate to severe tardive dyskinesia. The purpose of part B is to establish the durability of effect of SD-809 following 1-week period of randomized withdrawal (SD-809 and placebo), followed by 12 weeks of maintenance with SD-809.

Detailed Description: Participants who complete study SD-809-C-18 (NCT02195700), SD-809-C-23 (NCT02291861), or any other SD-809 study will be enrolled in this study. This study include a screening period (Part A), a titration period (Part A), a long-term treatment period (Part A), a double-blind, randomized withdrawal period (Part B), treatment after completion of the randomized withdrawal period (Part B), and a post-treatment safety follow-up period (Part A and Part B). EU participants who complete Part B will be invited to participate in Part C.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 343

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
Participant has successfully completed a controlled study of SD-809 for treatment of moderate to severe tardive dyskinesia
Participants 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 participants 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 (other than Study C-18, Study C-23, or any other eligible TEV-50717 parent study) 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A: SD-809	SD-809	Participants will receive SD-809 orally twice daily (BID) starting at 12 mg/day, which will be titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who decline to participate in Part B, will continue at their stable dose of SD-809 BID up to Week 158.
Part B: Placebo	SD-809	Participants will receive placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter will receive SD-809 (stable dose) for 12 weeks.
Part B: Placebo	Placebo	Participants will receive placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter will receive SD-809 (stable dose) for 12 weeks.
Part B: SD-809	SD-809	Participants will receive SD-809 (stable dose) for 1 week in randomized withdrawal period and will continue to receive the same dose of SD-809 for an additional 12 weeks.
Part C: SD-809	SD-809	EU participants who complete Part B and willing to continue in the study will continue treatment with SD-809 for 52 weeks at the dose administered during the 12-week open-label period of Part B.

Primary Outcome Measures

Name	Time	Method
Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal	Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days)	AEs were analyzed as one group combined for parts A and B per planned analysis. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE=prevents normal daily activities. Drug-related TEAEs: TEAEs with possible, probable, or definite relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A treatment-emergent AE was defined as an AE that began after the first administration of study medication or existing AEs that worsened after the first dose of study medication. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Part B: Change From Day 1 Visit in Total Motor AIMS Score at Day 7 Visit, as Assessed by Blinded Central Video Rating	Day 1 of Part B, Day 7 of Part B	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.

Secondary Outcome Measures

Name	Time	Method
Part A: Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating	Baseline, Week 145	The AIMS is an assessment tool used to detect and follow the severity of tardive dyskinesia (TD) over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating	Baseline, Week 158	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating	Baseline, Week 145	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating	Baseline, Week 158	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Percentage of Participants Who Had a 50% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating	Baseline to Week 145	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Percentage of Participants Who Had a 70% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating	Baseline to Week 145	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
Part A: Change From Baseline in AIMS Items 8, 9, and 10 Score at Week 145, as Assessed by the Site Rating	Baseline, Week 145	The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. Items 8 to 10 deal with global severity as judged by the examiner, and the participant's awareness of the movements and the distress associated with them. Item 8 (used as an overall severity index indicating severity of abnormal movements) was rated on a 5-point anchored scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 9 and 10 (provide additional information with regard to participant's incapacitation due to abnormal movements and participant's awareness of abnormal movements) were rated on a 5-point anchored scale ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Higher scores indicated more severe disease.
Part A: Percentage of Participants Who Were a Treatment Success, Based on the Clinical Global Impression of Change (CGIC)	Baseline up to Week 145	A treatment success was defined as much or very much improved on the CGIC from baseline of this study. The CGIC is a single-item questionnaire that asks the investigator to assess a participant's TD symptoms at specific visits/weeks after initiating therapy. The CGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.
Part A: Percentage of Participants Who Were a Treatment Success, Based on the Patient Global Impression of Change (PGIC)	Baseline up to Week 145	A treatment success was defined as much or very much improved on the PGIC from baseline of this study. The PGIC is single-item questionnaire that asks the participant to assess their TD symptoms at specific visits/weeks after initiating therapy. The PGIC uses a 7-point Likert scale, ranging from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = not changed, 1 = minimally improved, 2 = much improved, 3 = very much improved), to assess overall response to therapy.
Part A: Change From Baseline in Modified CDQ-24 Score at Week 158	Baseline, Week 158	The CDQ-24 is a disease-specific quality of life questionnaire developed for use in participants with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ-24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. The following domains were evaluated in the mCDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by participants on a scale of 0 = never or no impairment to 4 = always or very severe impairment. Total score ranged from 0 - 96, with higher score indicative of severe impairment.

Trial Locations

Locations (82): Teva Investigational Site 145
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Tuscaloosa, Alabama, United States
Teva Investigational Site 107
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Anaheim, California, United States
Teva Investigational Site 108
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Anaheim, California, United States
Teva Investigational Site 123
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Glendale, California, United States
Teva Investigational Site 160
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Irvine, California, United States
Teva Investigational Site 176
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Loma Linda, California, United States
Teva Investigational Site 121
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Los Angeles, California, United States
Teva Investigational Site 147
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Los Angeles, California, United States
Teva Investigational Site 174
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Norwalk, California, United States
Teva Investigational Site 130
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Oceanside, California, United States
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Teva Investigational Site 145
🇺🇸Tuscaloosa, Alabama, United States