Reducing Involuntary Movements in Participants With Tardive Dyskinesia

NCT02198794 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: SD-809-C-202014-001891-73
• Study Type: interventional
• Target: 343
• Locations: 6 countries
• Sites: 82

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.

Conditions

Tardive Dyskinesia

Keywords

Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Day 1 of Part B, Day 7 of Part B

Secondary Outcomes (10)

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

  Baseline, Week 145

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

  Baseline, Week 158

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

  Baseline, Week 145

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

  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

  Baseline to Week 145

Study Arms (4)

Part A: SD-809

EXPERIMENTAL

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.

Drug: SD-809

Part B: Placebo

PLACEBO COMPARATOR

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.

Drug: SD-809; Drug: Placebo

Part B: SD-809

ACTIVE COMPARATOR

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.

Drug: SD-809

Part C: SD-809

EXPERIMENTAL

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.

Drug: SD-809

Interventions

SD-809 DRUG

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

Also known as: Deutetrabenazine; TEV-50717

Part A: SD-809; Part B: Placebo; Part B: SD-809; Part C: SD-809

Placebo DRUG

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

Part B: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Auspex Pharmaceuticals, Inc.: lead

Study Sites (82)

Teva Investigational Site 145

Tuscaloosa, Alabama, 35404, United States

Location

Teva Investigational Site 107

Anaheim, California, 92804, United States

Location

Teva Investigational Site 108

Anaheim, California, 92805, United States

Location

Teva Investigational Site 123

Glendale, California, 91206, United States

Location

Teva Investigational Site 160

Irvine, California, 92614, United States

Location

Teva Investigational Site 176

Loma Linda, California, 92354, United States

Location

Teva Investigational Site 121

Los Angeles, California, 90033, United States

Location

Teva Investigational Site 147

Los Angeles, California, 90095-1769, United States

Location

Teva Investigational Site 174

Norwalk, California, 90650, United States

Location

Teva Investigational Site 130

Oceanside, California, 92056, United States

Location

Teva Investigational Site 102

Orange, California, 92868, United States

Location

Teva Investigational Site 104

San Bernardino, California, 92408, United States

Location

Teva Investigational Site 110

San Diego, California, 92108, United States

Location

Teva Investigational Site 169

San Rafael, California, 94901, United States

Location

Teva Investigational Site 129

Englewood, Colorado, 80113, United States

Location

Teva Investigational Site 139

New Haven, Connecticut, 06519, United States

Location

Teva Investigational Site 156

Washington D.C., District of Columbia, 20007, United States

Location

Teva Investigational Site 157

Boca Raton, Florida, 33486, United States

Location

Teva Investigational Site 117

Gainesville, Florida, 32607, United States

Location

Teva Investigational Site 150

Lake City, Florida, 32025, United States

Location

Teva Investigational Site 153

Miami, Florida, 33135, United States

Location

Teva Investigational Site 162

Miami, Florida, 33165, United States

Location

Teva Investigational Site 112

Orlando, Florida, 32803, United States

Location

Teva Investigational Site 144

Port Charlotte, Florida, 33980, United States

Location

Teva Investigational Site 155

Augusta, Georgia, 30912, United States

Location

Teva Investigational Site 165

Decatur, Georgia, 30033, United States

Location

Teva Investigational Site 131

Chicago, Illinois, 60611, United States

Location

Teva Investigational Site 154

Baltimore, Maryland, 21287, United States

Location

Teva Investigational Site 101

Glen Burnie, Maryland, 21061, United States

Location

Teva Investigational Site 118

Creve Coeur, Missouri, 63141, United States

Location

Teva Investigational Site 142

Kansas City, Missouri, 64108, United States

Location

Teva Investigational Site 175

St Louis, Missouri, 63104, United States

Location

Teva Investigational Site 161

St Louis, Missouri, 63109, United States

Location

Teva Investigational Site 178

Lincoln, Nebraska, 68526-9467, United States

Location

Teva Investigational Site 128

Albuquerque, New Mexico, 87106, United States

Location

Teva Investigational Site 146

Raleigh, North Carolina, 27610, United States

Location

Teva Investigational Site 114

Garfield Heights, Ohio, 44125, United States

Location

Teva Investigational Site 133

Charleston, South Carolina, 29425, United States

Location

Teva Investigational Site 149

Memphis, Tennessee, 38163, United States

Location

Teva Investigational Site 151

Fort Worth, Texas, 76104, United States

Location

Teva Investigational Site 115

Salt Lake City, Utah, 84105, United States

Location

Teva Investigational Site 141

Salt Lake City, Utah, 84108, United States

Location

Teva Investigational Site 167

Richland, Washington, 99352, United States

Location

Teva Investigational Site 166

Waukesha, Wisconsin, 53188, United States

Location

Teva Investigational Site 559

Havířov, 736 01, Czechia

Location

Teva Investigational Site 556

Hostivice, 999999, Czechia

Location

Teva Investigational Site 535

Litoměřice, 412 01, Czechia

Location

Teva Investigational Site 557

Pilsen, 312 00, Czechia

Location

Teva Investigational Site 533

Prague, 100 00, Czechia

Location

Teva Investigational Site 530

Prague, 16000, Czechia

Location

Teva Investigational Site 502

Gera, 07551, Germany

Location

Teva Investigational Site 504

Mainz, 55131, Germany

Location

Teva Investigational Site 540

Balassagyarmat, 999999, Hungary

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Teva Investigational Site 538

Budapest, 1135, Hungary

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Teva Investigational Site 541

Budapest, 1148, Hungary

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Teva Investigational Site 539

Doba, 8482, Hungary

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Teva Investigational Site 546

Győr, H-9024, Hungary

Location

Teva Investigational Site 545

Kalocsa, 6300, Hungary

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Teva Investigational Site 514

Bełchatów, 97-400, Poland

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Teva Investigational Site 554

Bialystok, 15-756, Poland

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Teva Investigational Site 510

Bydgoszcz, 85-015, Poland

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Teva Investigational Site 519

Bydgoszcz, 85-080, Poland

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Teva Investigational Site 536

Bydgoszcz, 85-156, Poland

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Teva Investigational Site 523

Chełmno, 86-200, Poland

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Teva Investigational Site 517

Choroszcz, 16-070, Poland

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Teva Investigational Site 513

Gdansk, 80-952, Poland

Location

Teva Investigational Site 512

Katowice, 40-097, Poland

Location

Teva Investigational Site 552

Katowice, 40-123, Poland

Location

Teva Investigational Site 520

Krakow, 30-349, Poland

Location

Teva Investigational Site 509

Krakow, 31-505, Poland

Location

Teva Investigational Site 508

Lodz, 90-130, Poland

Location

Teva Investigational Site 511

Lublin, 20-064, Poland

Location

Teva Investigational Site 524

Lublin, 20-831, Poland

Location

Teva Investigational Site 549

Olsztyn, 10-443, Poland

Location

Teva Investigational Site 522

Torun, 87-100, Poland

Location

Teva Investigational Site 550

Warsaw, 00-465, Poland

Location

Teva Investigational Site 516

Wroclaw, 50-227, Poland

Location

Teva Investigational Site 529

Bratislava, 826 06, Slovakia

Location

Teva Investigational Site 525

Domaša, 935 61, Slovakia

Location

Teva Investigational Site 527

Košice, 04017, Slovakia

Location

Teva Investigational Site 528

Rimavská Sobota, 979 12, Slovakia

Location

Teva Investigational Site 526

Rožňava, 04801, Slovakia

Location

Related Publications (2)

• Frank S, Anderson KE, Fernandez HH, Hauser RA, Claassen DO, Stamler D, Factor SA, Jimenez-Shahed J, Barkay H, Wilhelm A, Alexander JK, Chaijale N, Barash S, Savola JM, Gordon MF, Chen M. Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated with Huntington Disease. Neurol Ther. 2024 Jun;13(3):655-675. doi: 10.1007/s40120-024-00600-1. Epub 2024 Apr 1.

  PMID: 38557959 DERIVED

• Fernandez HH, Stamler D, Davis MD, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog LF, Woods SW, Bega D, LeDoux MS, Shprecher DR, Anderson KE. Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia. J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1317-1323. doi: 10.1136/jnnp-2018-319918. Epub 2019 Jul 10.

  PMID: 31296586 DERIVED

MeSH Terms

Conditions

Tardive Dyskinesia; Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms

Interventions

deutetrabenazine

Condition Hierarchy (Ancestors)

Dyskinesia, Drug-Induced; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert, M.D.

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: July 24, 2014
• Study Start: October 20, 2014
• Primary Completion: December 6, 2019
• Study Completion: December 14, 2020
• Last Updated: April 1, 2022
• Results First Posted: March 1, 2021

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

CZ (6); HU (6); PL (19); SL (5); US (44); DE (2)