Aim to Reduce Movements in Tardive Dyskinesia (ARM-TD)

• ClinicalTrials.gov Identifier: NCT02195700
• Recruitment Status: Completed
• First Posted: July 21, 2014
• Results First Posted: March 20, 2018
• Last Update Posted: November 9, 2021
• Sponsor: Auspex Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Teva Branded Pharmaceutical Products R&D, Inc. ( Auspex Pharmaceuticals, Inc. )

Study Description

Brief Summary:

The purpose of this study is to determine whether an investigational drug, SD-809 (deutetrabenazine), will reduce the severity of abnormal involuntary movements of tardive dyskinesia.

Condition or disease	Intervention/treatment	Phase
Tardive Dyskinesia	Drug: SD-809; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia
• Actual Study Start Date: June 2014
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: SD-809; SD-809 tablets taken twice daily for 12 weeks.	Drug: SD-809; SD-809 tablets taken twice daily for 12 weeks, includes a dose titration period and maintenance period.; Other Names: deutetrabenazine; AUSTEDO®
Placebo Comparator: Sugar Pill; Placebo tablets taken twice daily for 12 weeks.	Drug: Placebo; Placebo tablets taken twice daily for 12 weeks.

Outcome Measures

Primary Outcome Measures :

1. Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis [ Time Frame: Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12 ]

   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. AIMS 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, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.

   A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point, treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. An unstructured covariance model was used.

Secondary Outcome Measures :

1. Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC) [ Time Frame: Week 12 ]
   The CGIC is a single-item questionnaire that asks the investigator to assess a patient's TD symptoms at specific visits after initiating therapy. The CGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as "much improved" or "very much improved" at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not "much improved" or "very much improved" at the week 12 visit, were considered treatment failures.
2. Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC) [ Time Frame: Week 12 ]
   The PGIC is a single-item questionnaire that asks the patient to assess their TD symptoms at specific visits after initiating therapy. The PGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as "much improved" or "very much improved" at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not "much improved" or "very much improved" at the week 12 visit, were considered treatment failures.
3. Change From Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24) [ Time Frame: Day 0 (Baseline), Week 12 with last observation carried forward ]
   The CDQ-24 is a disease-specific quality of life questionnaire developed for use in patients 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 are evaluated in the CDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 (no impairment) to 96 (severe impairment). Negative change from baseline scores indicate improvement.
4. Participants With Adverse Events for the Overall Treatment Period [ Time Frame: Day 1 to Week 12 ]
   An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator and includes possibly, probably and definitely related categories. Serious AEs (SAE) include death, a life-threatening adverse event, 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 the patient and required medical intervention to prevent the previously listed serious outcomes.
5. Percentage Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis [ Time Frame: Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12 ]

   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. AIMS 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, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative percent change from baseline score indicates improvement.

   The MMRM model includes fixed effects for treatment, time point (weeks 2, 4, 6, 9, 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. Patient is a random effect.

6. Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12 [ Time Frame: Day 0 (Baseline), Week 12 ]

   Response level represents the % improvement in AIMS from baseline. 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. AIMS 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, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia).

   Patients with a missing AIMS score were considered to be AIMS nonresponders.

7. Change in Locally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis [ Time Frame: Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12 ]

   This outcome is similar to the primary outcome except that AIMS was read locally.

   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. This outcome reports the local reading of AIMS data.

   This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.

   A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point (weeks 2, 4, 6, 9, and 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (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
• 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 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 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

Contacts and Locations

Locations

United States, Alabama

Tuscaloosa, Alabama, United States

United States, California

Anaheim, California, United States

Glendale, California, United States

Oceanside, California, United States

Orange, California, United States

San Bernardino, California, United States

San Diego, California, United States

United States, Colorado

Denver, Colorado, United States

United States, Connecticut

New Haven, Connecticut, United States

Stamford, Connecticut, United States

United States, District of Columbia

Washington, District of Columbia, United States

United States, Florida

Boca Raton, Florida, United States

Gainesville, Florida, United States

Lake City, Florida, United States

Miami, Florida, United States

Orlando, Florida, United States

Port Charlotte, Florida, United States

United States, Illinois

Chicago, Illinois, United States

United States, Maryland

Baltimore, Maryland, United States

United States, Minnesota

Minneapolis, Minnesota, United States

United States, Missouri

Kansas City, Missouri, United States

Saint Louis, Missouri, United States

United States, New Mexico

Albuquerque, New Mexico, United States

United States, North Carolina

Asheville, North Carolina, United States

Durham, North Carolina, United States

Raleigh, North Carolina, United States

United States, Ohio

Cleveland, Ohio, United States

United States, Pennsylvania

Philadelphia, Pennsylvania, United States

United States, South Carolina

Charleston, South Carolina, United States

United States, Tennessee

Memphis, Tennessee, United States

United States, Texas

Fort Worth, Texas, United States

United States, Utah

Salt Lake City, Utah, United States

Czechia

Prague, Czechia

Poland

Gdansk, Poland

Katowice, Poland

Krakow, Poland

Lodz, Poland

Lublin, Poland

Torun, Poland

Slovakia

Hronovce, Slovakia

Roznava, Slovakia

Sponsors and Collaborators

Auspex Pharmaceuticals, Inc.

Investigators

• Study Director: Teva Medical Expert, M.D.; Teva Branded Pharmaceutical Products R&D, Inc.

More Information

• Responsible Party: Auspex Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02195700
• Other Study ID Numbers: SD-809-C-18
• First Posted: July 21, 2014
• Results First Posted: March 20, 2018
• Last Update Posted: November 9, 2021
• Last Verified: November 2021

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:

Dyskinesias; Tardive Dyskinesia; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Dyskinesia, Drug-Induced