Addressing Involuntary Movements in Tardive Dyskinesia

NCT02291861 | Completed Phase 3 Results DMC

• 2 other identifiers: SD-809-C-232014-003135-19
• Study Type: interventional
• Target: 298
• Locations: 6 countries
• Sites: 106

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.

Conditions

Tardive Dyskinesia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model For Repeated Measures (MMRM)

  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.

  Day 0 (Baseline), Weeks 2, 4, 8 and 12

Secondary Outcomes (7)

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

  Week 12

• Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score From Baseline to Week 12

  Day 0 (Baseline), Week 12

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

  Week 12

• 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

• 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

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo tablets taken twice daily for 12 weeks.

Drug: Placebo

SD-809 12 mg/day

EXPERIMENTAL

SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.

Drug: SD-809

SD-809 24 mg/day

EXPERIMENTAL

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 36 mg/day

EXPERIMENTAL

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

Interventions

SD-809 DRUG

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.

Also known as: deutetrabenzine, Austedo

SD-809 12 mg/day; SD-809 24 mg/day; SD-809 36 mg/day

Placebo DRUG

Placebo tablets taken twice daily for 12 weeks. Tablets were swallowed whole with water and taken with food.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 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
• 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

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 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

Sponsors & Collaborators

• Auspex Pharmaceuticals, Inc.: lead

Study Sites (106)

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 177

Imperial, California, 92251, United States

Location

Teva Investigational Site 160

Irvine, California, 92614, United States

Location

Teva Investigational Site 106

Irvine, California, 92697, 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 170

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 113

Chicago, Illinois, 60612, United States

Location

Teva Investigational Site 164

Kansas City, Kansas, 66160, 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 135

Boston, Massachusetts, 02215, 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 172

Commack, New York, 11725, United States

Location

Teva Investigational Site 148

New York, New York, 10032, United States

Location

Teva Investigational Site 138

Asheville, North Carolina, 28805, United States

Location

Teva Investigational Site 146

Raleigh, North Carolina, 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 168

Burlington, Vermont, 05401, United States

Location

Teva Investigational Site 171

Charlottesville, Virginia, 22903, 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, Czechia

Location

Teva Investigational Site 558

Hradec Králové, 503 41, 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

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Teva Investigational Site 532

Prague, 158 00, Czechia

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Teva Investigational Site 530

Prague, 16000, Czechia

Location

Teva Investigational Site 531

Prague, 181 02, Czechia

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Teva Investigational Site 534

Prague, 190 00, Czechia

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Teva Investigational Site 502

Gera, 07551, Germany

Location

Teva Investigational Site 503

Haag in Oberbayern, 83527, Germany

Location

Teva Investigational Site 504

Mainz, 55131, Germany

Location

Teva Investigational Site 507

Prien am Chiemsee, 83209, Germany

Location

Teva Investigational Site 544

Taufkirchen, 84416, Germany

Location

Teva Investigational Site 501

Wolfach, 77709, Germany

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Teva Investigational Site 540

Balassagyarmat, 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 537

Budapest, 1204, Hungary

Location

Teva Investigational Site 542

Budapest, H-1135, Hungary

Location

Teva Investigational Site 539

Doba, 8482, Hungary

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Teva Investigational Site 546

Győr, 9024, Hungary

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Teva Investigational Site 545

Kalocsa, 6300, Hungary

Location

Teva Investigational Site 547

Szeged, 6725, Hungary

Location

Teva Investigational Site 514

Bełchatów, 97-400, Poland

Location

Teva Investigational Site 554

Bialystok, 15-756, Poland

Location

Teva Investigational Site 510

Bydgoszcz, 85-015, Poland

Location

Teva Investigational Site 519

Bydgoszcz, 85-080, Poland

Location

Teva Investigational Site 536

Bydgoszcz, 85-156, Poland

Location

Teva Investigational Site 523

Chełmno, 86-200, Poland

Location

Teva Investigational Site 517

Choroszcz, 16-070, Poland

Location

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

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Teva Investigational Site 511

Lublin, 20-064, Poland

Location

Teva Investigational Site 515

Lublin, 20-090, Poland

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Teva Investigational Site 524

Lublin, 20-831, Poland

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Teva Investigational Site 549

Olsztyn, 10-443, Poland

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Teva Investigational Site 521

Pruszków, 05-802, Poland

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Teva Investigational Site 518

Sosnowiec, 41-200, Poland

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Teva Investigational Site 522

Torun, 87-100, Poland

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Teva Investigational Site 550

Warsaw, 00-465, Poland

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Teva Investigational Site 555

Warsaw, 00-669, 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)

• Anderson KE, Stamler D, Davis MD, Factor SA, Hauser RA, Isojarvi J, Jarskog LF, Jimenez-Shahed J, Kumar R, McEvoy JP, Ochudlo S, Ondo WG, Fernandez HH. Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Psychiatry. 2017 Aug;4(8):595-604. doi: 10.1016/S2215-0366(17)30236-5. Epub 2017 Jun 28.

  PMID: 28668671 RESULT

• 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

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

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Teva Medical Expert, MD

  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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2014
• First Posted: November 17, 2014
• Study Start: October 31, 2014
• Primary Completion: August 19, 2016
• Study Completion: August 19, 2016
• Last Updated: November 9, 2021
• Results First Posted: April 11, 2018

Record last verified: 2021-11

Locations

US (53); CZ (10); HU (9); PL (23); DE (6); SL (5)