Reducing Involuntary Movements in Participants With Tardive Dyskinesia

Tardive Dyskinesia Clinical Trial

— RIM-TD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02198794
• Other study ID #: SD-809-C-20
• Secondary ID: 2014-001891-73
• Status: Completed
• Phase: Phase 3
• Start date: October 20, 2014
• Est. completion date: December 14, 2020

Study information

• Verified date: March 2022
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 343
• Est. completion date: December 14, 2020
• Est. primary completion date: December 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dyskinesias
• Tardive Dyskinesia

Intervention

Drug:
• SD-809
SD-809 will be administered per dose and schedule specified in the arm.
• Placebo
Placebo matching to SD-809 will be administered per schedule specified in the arm.

Locations

Country	Name	City	State
Czechia	Teva Investigational Site 559	Havirov
Czechia	Teva Investigational Site 556	Hostivice
Czechia	Teva Investigational Site 535	Litomerice
Czechia	Teva Investigational Site 557	Plzen
Czechia	Teva Investigational Site 533	Prague 10
Czechia	Teva Investigational Site 530	Prague 6
Germany	Teva Investigational Site 502	Gera
Germany	Teva Investigational Site 504	Mainz
Hungary	Teva Investigational Site 540	Balassagyarmat
Hungary	Teva Investigational Site 538	Budapest
Hungary	Teva Investigational Site 541	Budapest
Hungary	Teva Investigational Site 539	Doba
Hungary	Teva Investigational Site 546	Gyor
Hungary	Teva Investigational Site 545	Kalocsa
Poland	Teva Investigational Site 514	Belchatow
Poland	Teva Investigational Site 554	Bialystok
Poland	Teva Investigational Site 510	Bydgoszcz
Poland	Teva Investigational Site 519	Bydgoszcz
Poland	Teva Investigational Site 536	Bydgoszcz
Poland	Teva Investigational Site 523	Chelmno
Poland	Teva Investigational Site 517	Choroszcz
Poland	Teva Investigational Site 513	Gdansk
Poland	Teva Investigational Site 512	Katowice
Poland	Teva Investigational Site 552	Katowice
Poland	Teva Investigational Site 509	Krakow
Poland	Teva Investigational Site 520	Krakow
Poland	Teva Investigational Site 508	Lodz
Poland	Teva Investigational Site 511	Lublin
Poland	Teva Investigational Site 524	Lublin
Poland	Teva Investigational Site 549	Olsztyn
Poland	Teva Investigational Site 522	Torun
Poland	Teva Investigational Site 550	Warszawa
Poland	Teva Investigational Site 516	Wroclaw
Slovakia	Teva Investigational Site 529	Bratislava
Slovakia	Teva Investigational Site 525	Hronovce
Slovakia	Teva Investigational Site 527	Kosice
Slovakia	Teva Investigational Site 528	Rimavska Sobota
Slovakia	Teva Investigational Site 526	Roznava
United States	Teva Investigational Site 128	Albuquerque	New Mexico
United States	Teva Investigational Site 107	Anaheim	California
United States	Teva Investigational Site 108	Anaheim	California
United States	Teva Investigational Site 155	Augusta	Georgia
United States	Teva Investigational Site 154	Baltimore	Maryland
United States	Teva Investigational Site 157	Boca Raton	Florida
United States	Teva Investigational Site 133	Charleston	South Carolina
United States	Teva Investigational Site 131	Chicago	Illinois
United States	Teva Investigational Site 118	Creve Coeur	Missouri
United States	Teva Investigational Site 165	Decatur	Georgia
United States	Teva Investigational Site 129	Englewood	Colorado
United States	Teva Investigational Site 151	Fort Worth	Texas
United States	Teva Investigational Site 117	Gainesville	Florida
United States	Teva Investigational Site 114	Garfield Heights	Ohio
United States	Teva Investigational Site 101	Glen Burnie	Maryland
United States	Teva Investigational Site 123	Glendale	California
United States	Teva Investigational Site 160	Irvine	California
United States	Teva Investigational Site 142	Kansas City	Missouri
United States	Teva Investigational Site 150	Lake City	Florida
United States	Teva Investigational Site 178	Lincoln	Nebraska
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 149	Memphis	Tennessee
United States	Teva Investigational Site 153	Miami	Florida
United States	Teva Investigational Site 162	Miami	Florida
United States	Teva Investigational Site 139	New Haven	Connecticut
United States	Teva Investigational Site 174	Norwalk	California
United States	Teva Investigational Site 130	Oceanside	California
United States	Teva Investigational Site 102	Orange	California
United States	Teva Investigational Site 112	Orlando	Florida
United States	Teva Investigational Site 144	Port Charlotte	Florida
United States	Teva Investigational Site 146	Raleigh	North Carolina
United States	Teva Investigational Site 167	Richland	Washington
United States	Teva Investigational Site 161	Saint Louis	Missouri
United States	Teva Investigational Site 175	Saint Louis	Missouri
United States	Teva Investigational Site 115	Salt Lake City	Utah
United States	Teva Investigational Site 141	Salt Lake City	Utah
United States	Teva Investigational Site 104	San Bernardino	California
United States	Teva Investigational Site 110	San Diego	California
United States	Teva Investigational Site 169	San Rafael	California
United States	Teva Investigational Site 145	Tuscaloosa	Alabama
United States	Teva Investigational Site 156	Washington	District of Columbia
United States	Teva Investigational Site 166	Waukesha	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Auspex Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Hungary,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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