Reducing Involuntary Movements in Participants With Tardive Dyskinesia (RIM-TD)

An Open-Label, Long-Term Safety Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia

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.

Study Overview

• Status: Completed
• Conditions: Tardive Dyskinesia
• Intervention / Treatment: Drug: SD-809; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 343
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Havirov, Czechia, 736 01
    • Teva Investigational Site 559
  • Hostivice, Czechia, 999999
    • Teva Investigational Site 556
  • Litomerice, Czechia, 412 01
    • Teva Investigational Site 535
  • Plzen, Czechia, 312 00
    • Teva Investigational Site 557
  • Prague 10, Czechia, 100 00
    • Teva Investigational Site 533
  • Prague 6, Czechia, 16000
    • Teva Investigational Site 530
• Germany
  • Gera, Germany, 07551
    • Teva Investigational Site 502
  • Mainz, Germany, 55131
    • Teva Investigational Site 504
• Hungary
  • Balassagyarmat, Hungary, 999999
    • Teva Investigational Site 540
  • Budapest, Hungary, 1135
    • Teva Investigational Site 538
  • Budapest, Hungary, 1148
    • Teva Investigational Site 541
  • Doba, Hungary, 8482
    • Teva Investigational Site 539
  • Gyor, Hungary, H-9024
    • Teva Investigational Site 546
  • Kalocsa, Hungary, 6300
    • Teva Investigational Site 545
• Poland
  • Belchatow, Poland, 97-400
    • Teva Investigational Site 514
  • Bialystok, Poland, 15-756
    • Teva Investigational Site 554
  • Bydgoszcz, Poland, 85-015
    • Teva Investigational Site 510
  • Bydgoszcz, Poland, 85-080
    • Teva Investigational Site 519
  • Bydgoszcz, Poland, 85-156
    • Teva Investigational Site 536
  • Chelmno, Poland, 86-200
    • Teva Investigational Site 523
  • Choroszcz, Poland, 16-070
    • Teva Investigational Site 517
  • Gdansk, Poland, 80-952
    • Teva Investigational Site 513
  • Katowice, Poland, 40-097
    • Teva Investigational Site 512
  • Katowice, Poland, 40-123
    • Teva Investigational Site 552
  • Krakow, Poland, 30-349
    • Teva Investigational Site 520
  • Krakow, Poland, 31-505
    • Teva Investigational Site 509
  • Lodz, Poland, 90-130
    • Teva Investigational Site 508
  • Lublin, Poland, 20-064
    • Teva Investigational Site 511
  • Lublin, Poland, 20-831
    • Teva Investigational Site 524
  • Olsztyn, Poland, 10-443
    • Teva Investigational Site 549
  • Torun, Poland, 87-100
    • Teva Investigational Site 522
  • Warszawa, Poland, 00-465
    • Teva Investigational Site 550
  • Wroclaw, Poland, 50-227
    • Teva Investigational Site 516
• Slovakia
  • Bratislava, Slovakia, 826 06
    • Teva Investigational Site 529
  • Hronovce, Slovakia, 935 61
    • Teva Investigational Site 525
  • Kosice, Slovakia, 04017
    • Teva Investigational Site 527
  • Rimavska Sobota, Slovakia, 979 12
    • Teva Investigational Site 528
  • Roznava, Slovakia, 04801
    • Teva Investigational Site 526
• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35404
      • Teva Investigational Site 145
  • California
    • Anaheim, California, United States, 92804
      • Teva Investigational Site 107
    • Anaheim, California, United States, 92805
      • Teva Investigational Site 108
    • Glendale, California, United States, 91206
      • Teva Investigational Site 123
    • Irvine, California, United States, 92614
      • Teva Investigational Site 160
    • Loma Linda, California, United States, 92354
      • Teva Investigational Site 176
    • Los Angeles, California, United States, 90033
      • Teva Investigational Site 121
    • Los Angeles, California, United States, 90095-1769
      • Teva Investigational Site 147
    • Norwalk, California, United States, 90650
      • Teva Investigational Site 174
    • Oceanside, California, United States, 92056
      • Teva Investigational Site 130
    • Orange, California, United States, 92868
      • Teva Investigational Site 102
    • San Bernardino, California, United States, 92408
      • Teva Investigational Site 104
    • San Diego, California, United States, 92108
      • Teva Investigational Site 110
    • San Rafael, California, United States, 94901
      • Teva Investigational Site 169
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Teva Investigational Site 129
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Teva Investigational Site 139
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Teva Investigational Site 156
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Teva Investigational Site 157
    • Gainesville, Florida, United States, 32607
      • Teva Investigational Site 117
    • Lake City, Florida, United States, 32025
      • Teva Investigational Site 150
    • Miami, Florida, United States, 33135
      • Teva Investigational Site 153
    • Miami, Florida, United States, 33165
      • Teva Investigational Site 162
    • Orlando, Florida, United States, 32803
      • Teva Investigational Site 112
    • Port Charlotte, Florida, United States, 33980
      • Teva Investigational Site 144
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Teva Investigational Site 155
    • Decatur, Georgia, United States, 30033
      • Teva Investigational Site 165
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Teva Investigational Site 131
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Teva Investigational Site 154
    • Glen Burnie, Maryland, United States, 21061
      • Teva Investigational Site 101
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Teva Investigational Site 118
    • Kansas City, Missouri, United States, 64108
      • Teva Investigational Site 142
    • Saint Louis, Missouri, United States, 63104
      • Teva Investigational Site 175
    • Saint Louis, Missouri, United States, 63109
      • Teva Investigational Site 161
  • Nebraska
    • Lincoln, Nebraska, United States, 68526-9467
      • Teva Investigational Site 178
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Teva Investigational Site 128
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • Teva Investigational Site 146
  • Ohio
    • Garfield Heights, Ohio, United States, 44125
      • Teva Investigational Site 114
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Teva Investigational Site 133
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • Teva Investigational Site 149
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Teva Investigational Site 151
  • Utah
    • Salt Lake City, Utah, United States, 84105
      • Teva Investigational Site 115
    • Salt Lake City, Utah, United States, 84108
      • Teva Investigational Site 141
  • Washington
    • Richland, Washington, United States, 99352
      • Teva Investigational Site 167
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • Teva Investigational Site 166

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part A: 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.	Drug: SD-809; SD-809 will be administered per dose and schedule specified in the arm.; Other Names: Deutetrabenazine; TEV-50717
PLACEBO_COMPARATOR: Part B: 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.	Drug: SD-809; SD-809 will be administered per dose and schedule specified in the arm.; Other Names: Deutetrabenazine; TEV-50717; Drug: Placebo; Placebo matching to SD-809 will be administered per schedule specified in the arm.
ACTIVE_COMPARATOR: Part B: 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.	Drug: SD-809; SD-809 will be administered per dose and schedule specified in the arm.; Other Names: Deutetrabenazine; TEV-50717
EXPERIMENTAL: Part C: 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.	Drug: SD-809; SD-809 will be administered per dose and schedule specified in the arm.; Other Names: Deutetrabenazine; TEV-50717

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 145
Part A: Change From Baseline in Total Motor AIMS Score at Week 158, 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. 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.	Baseline, Week 158
Part A: Percent 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 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.	Baseline, Week 145
Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 158, 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. 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.	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	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.	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	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.	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.	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.	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.	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.	Baseline, Week 158

Collaborators and Investigators

• Sponsor: Auspex Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 20, 2014
• Primary Completion (ACTUAL): December 6, 2019
• Study Completion (ACTUAL): December 14, 2020

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: July 22, 2014
• First Posted (ESTIMATE): July 24, 2014

Study Record Updates

• Last Update Posted (ACTUAL): April 1, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Movement Disorders; Central Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Dyskinesias
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesia, Drug-Induced; Dyskinesias; Tardive Dyskinesia
• Other Study ID Numbers: SD-809-C-20; 2014-001891-73 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No