Addressing Involuntary Movements in Tardive Dyskinesia (AIM-TD)

November 5, 2021 updated by: Auspex Pharmaceuticals, Inc.

A Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

298

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Havirov, Czechia, 736 01
        • Teva Investigational Site 559
      • Hostivice, Czechia
        • Teva Investigational Site 556
      • Hradec Kralove, Czechia, 503 41
        • Teva Investigational Site 558
      • Litomerice, Czechia, 412 01
        • Teva Investigational Site 535
      • Plzen, Czechia, 312 00
        • Teva Investigational Site 557
      • Prague 6, Czechia, 16000
        • Teva Investigational Site 530
      • Prague 8, Czechia, 181 02
        • Teva Investigational Site 531
      • Praha 10, Czechia, 100 00
        • Teva Investigational Site 533
      • Praha 5, Czechia, 158 00
        • Teva Investigational Site 532
      • Praha 9, Czechia, 190 00
        • Teva Investigational Site 534
  • Germany
      • Gera, Germany, 07551
        • Teva Investigational Site 502
      • Haag In Oberbayern, Germany, 83527
        • Teva Investigational Site 503
      • Mainz, Germany, 55131
        • Teva Investigational Site 504
      • Prien am Chiemsee, Germany, 83209
        • Teva Investigational Site 507
      • Taufkirchen, Germany, 84416
        • Teva Investigational Site 544
      • Wolfach, Germany, 77709
        • Teva Investigational Site 501
  • Hungary
      • Balassagyarmat, Hungary
        • Teva Investigational Site 540
      • Budapest, Hungary, 1135
        • Teva Investigational Site 538
      • Budapest, Hungary, 1148
        • Teva Investigational Site 541
      • Budapest, Hungary, 1204
        • Teva Investigational Site 537
      • Budapest, Hungary, H-1135
        • Teva Investigational Site 542
      • Doba, Hungary, 8482
        • Teva Investigational Site 539
      • Gyor, Hungary, 9024
        • Teva Investigational Site 546
      • Kalocsa, Hungary, 6300
        • Teva Investigational Site 545
      • Szeged, Hungary, 6725
        • Teva Investigational Site 547
  • 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, 20-090
        • Teva Investigational Site 515
      • Lublin, Poland, 20-831
        • Teva Investigational Site 524
      • Olsztyn, Poland, 10-443
        • Teva Investigational Site 549
      • Pruszkow, Poland, 05-802
        • Teva Investigational Site 521
      • Sosnowiec, Poland, 41-200
        • Teva Investigational Site 518
      • Torun, Poland, 87-100
        • Teva Investigational Site 522
      • Warszawa, Poland, 00-465
        • Teva Investigational Site 550
      • Warszawa, Poland, 00-669
        • Teva Investigational Site 555
      • 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
      • Imperial, California, United States, 92251
        • Teva Investigational Site 177
      • Irvine, California, United States, 92614
        • Teva Investigational Site 160
      • Irvine, California, United States, 92697
        • Teva Investigational Site 106
      • 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 170
      • 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
      • Chicago, Illinois, United States, 60612
        • Teva Investigational Site 113
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Teva Investigational Site 164
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Teva Investigational Site 154
      • Glen Burnie, Maryland, United States, 21061
        • Teva Investigational Site 101
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Teva Investigational Site 135
    • 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
    • New York
      • Commack, New York, United States, 11725
        • Teva Investigational Site 172
      • New York, New York, United States, 10032
        • Teva Investigational Site 148
    • North Carolina
      • Asheville, North Carolina, United States, 28805
        • Teva Investigational Site 138
      • Raleigh, North Carolina, United States
        • Teva Investigational Site 146
    • 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
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Teva Investigational Site 168
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Teva Investigational Site 171
    • Washington
      • Richland, Washington, United States, 99352
        • Teva Investigational Site 167
    • Wisconsin
      • Waukesha, Wisconsin, United States, 53188
        • Teva Investigational Site 166

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (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
  • 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

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 or device within 30 days
  • Have acknowledged use of illicit drugs
  • Have a history of alcohol or substance abuse in the previous 12 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Placebo tablets taken twice daily for 12 weeks.
Drug: Placebo
Placebo tablets taken twice daily for 12 weeks. Tablets were swallowed whole with water and taken with food.
EXPERIMENTAL: SD-809 12 mg/day
SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
Drug: SD-809
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.
Other Names:
  • Austedo
  • deutetrabenzine
EXPERIMENTAL: SD-809 24 mg/day
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 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.
Other Names:
  • Austedo
  • deutetrabenzine
EXPERIMENTAL: SD-809 36 mg/day
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
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.
Other Names:
  • Austedo
  • deutetrabenzine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model For Repeated Measures (MMRM)
Time Frame: Day 0 (Baseline), Weeks 2, 4, 8 and 12

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients Considered 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.

The success 95% confidence interval (CI) was calculated with the Wilson (score) confidence limits.
Week 12
Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score From Baseline to Week 12
Time Frame: Day 0 (Baseline), Week 12

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 mCDQ-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 - 96. Negative change from baseline scores indicate improvement.

For patients with missing data at week 12, the baseline or last available value was used as the week 12 value.
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)
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. The success 95% CI was calculated with the Wilson (score) confidence limits.
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
Time Frame: Day 0 (Baseline), Week 12

Responders who had a 50% or greater improvement in total motor modified AIMS at Week 12 as compared to baseline were reported as a percentage of participants with an outcome at Week 12. The responder 95% CI is calculated with the Wilson (score) confidence limits.

AIMS is an assessment tool used to detect and follow the severity of 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.
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)
Time Frame: Day 0 (Baseline), Weeks 2, 4, 8 and 12

AIMS is an assessment tool used to detect and follow the severity of 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 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
Cumulative Percentage of Responders Based on Change in in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Recorded in Incremental Steps of 10 Percentage Points
Time Frame: Day 0 (Baseline), Week 12

AIMS is an assessment tool used to detect and follow the severity of TD over time, 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.

Participants with missing data are classified as non-responders. The responder 95% CI is calculated with the Wilson (score) confidence limits. If any of the expected cell counts are < 5, exact Clopper Pearson limits are presented.

Data report the percentage of participants who responded to the percentage improvement indicated in each row.
Day 0 (Baseline), Week 12
Participants With Adverse Events During 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.
Day 1 to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Auspex Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 31, 2014

Primary Completion (ACTUAL)

August 19, 2016

Study Completion (ACTUAL)

August 19, 2016

Study Registration Dates

First Submitted

November 12, 2014

First Submitted That Met QC Criteria

November 12, 2014

First Posted (ESTIMATE)

November 17, 2014

Study Record Updates

Last Update Posted (ACTUAL)

November 9, 2021

Last Update Submitted That Met QC Criteria

November 5, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SD-809-C-23
  • 2014-003135-19 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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