Reducing Involuntary Movements in Participants With Tardive Dyskinesia

Phase 3CompletedNCT02198794

Auspex Pharmaceuticals, Inc.343 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

343

Conditions

Tardive Dyskinesia

Interventions

SD-809DRUG

SD-809 will be administered per dose and schedule specified in the arm.

PlaceboDRUG

Placebo matching to SD-809 will be administered per schedule specified in the arm.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (82)

Outcomes

Primary Outcomes

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

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.

Time frame: 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)

Part B: Change From Day 1 Visit in Total Motor AIMS Score at Day 7 Visit, as Assessed by Blinded Central Video Rating

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.

Time frame: Day 1 of Part B, Day 7 of Part B

Secondary Outcomes

Part A: Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating

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.

Data from ClinicalTrials.gov

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Teva Investigational Site 145

Tuscaloosa, Alabama, United States

Teva Investigational Site 107

Anaheim, California, United States

Teva Investigational Site 108

Anaheim, California, United States

Teva Investigational Site 123

Glendale, California, United States

Teva Investigational Site 160

Irvine, California, United States

Teva Investigational Site 176

Loma Linda, California, United States

Teva Investigational Site 121

Los Angeles, California, United States

Teva Investigational Site 147

Los Angeles, California, United States

Teva Investigational Site 174

Norwalk, California, United States

Teva Investigational Site 130

Oceanside, California, United States

...and 72 more locations

Time frame: Baseline, Week 145

Part A: Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating

Time frame: Baseline, Week 158

Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating

Time frame: Baseline, Week 145

Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating

Time frame: Baseline, Week 158

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

Time frame: Baseline to Week 145

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

Time frame: Baseline to Week 145

Part A: Change From Baseline in AIMS Items 8, 9, and 10 Score at Week 145, as Assessed by the Site Rating

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.

Time frame: Baseline, Week 145

Part A: Percentage of Participants Who Were a Treatment Success, Based on the Clinical Global Impression of Change (CGIC)

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.

Time frame: Baseline up to Week 145

Part A: Percentage of Participants Who Were a Treatment Success, Based on the Patient Global Impression of Change (PGIC)

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.

Time frame: Baseline up to Week 145

Part A: Change From Baseline in Modified CDQ-24 Score at 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.

Time frame: Baseline, Week 158