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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02198794
Recruitment Status : Completed
First Posted : July 24, 2014
Results First Posted : March 1, 2021
Last Update Posted : April 1, 2022
Sponsor:
Information provided by (Responsible Party):
Teva Branded Pharmaceutical Products R&D, Inc. ( Auspex Pharmaceuticals, Inc. )

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.

Condition or disease Intervention/treatment Phase
Tardive Dyskinesia Drug: SD-809 Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 343 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Open-Label, Long-Term Safety Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia
Actual Study Start Date : October 20, 2014
Actual Primary Completion Date : December 6, 2019
Actual Study Completion Date : December 14, 2020

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: Deutetrabenazine; TEV-50717




Primary Outcome Measures :
  1. 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 [ 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) ]
    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.

  2. Part B: Change From Day 1 Visit in Total Motor AIMS Score at Day 7 Visit, as Assessed by Blinded Central Video Rating [ Time Frame: Day 1 of Part B, Day 7 of Part B ]
    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.


Secondary Outcome Measures :
  1. Part A: Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating [ Time Frame: Baseline, Week 145 ]
    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.

  2. Part A: Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating [ Time Frame: Baseline, Week 158 ]
    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.

  3. 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 ]
    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.

  4. 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 ]
    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.

  5. 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 ]
    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.

  6. 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 ]
    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.

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

  8. Part A: Percentage of Participants Who Were a Treatment Success, Based on the Clinical Global Impression of Change (CGIC) [ Time Frame: Baseline up to Week 145 ]
    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.

  9. Part A: Percentage of Participants Who Were a Treatment Success, Based on the Patient Global Impression of Change (PGIC) [ Time Frame: Baseline up to Week 145 ]
    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.

  10. Part A: Change From Baseline in Modified CDQ-24 Score at Week 158 [ Time Frame: Baseline, 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02198794


Locations
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Sponsors and Collaborators
Auspex Pharmaceuticals, Inc.
Investigators
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Study Director: Teva Medical Expert, M.D. Teva Branded Pharmaceutical Products R&D, Inc.
  Study Documents (Full-Text)

Documents provided by Teva Branded Pharmaceutical Products R&D, Inc. ( Auspex Pharmaceuticals, Inc. ):
Study Protocol  [PDF] May 2, 2018
Statistical Analysis Plan  [PDF] December 3, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Auspex Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02198794    
Other Study ID Numbers: SD-809-C-20
2014-001891-73 ( EudraCT Number )
First Posted: July 24, 2014    Key Record Dates
Results First Posted: March 1, 2021
Last Update Posted: April 1, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc. ( Auspex Pharmaceuticals, Inc. ):
Dyskinesias
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Additional relevant MeSH terms:
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Dyskinesias
Tardive Dyskinesia
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Dyskinesia, Drug-Induced