Addressing Involuntary Movements in Tardive Dyskinesia

Phase 3

Completed

Conditions: Tardive Dyskinesia

Interventions: Drug: SD-809
Drug: Placebo

Registration Number: NCT02291861

Lead Sponsor: Auspex Pharmaceuticals, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 298

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SD-809 24 mg/day	SD-809	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.
SD-809 36 mg/day	SD-809	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.
Placebo	Placebo	Placebo tablets taken twice daily for 12 weeks.
SD-809 12 mg/day	SD-809	SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model For Repeated Measures (MMRM)	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)	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.
Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score From Baseline to Week 12	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.
Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)	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.
Percentage of Participants Who Had a 50% or Greater Reduction in Total Motor Abnormal Involuntary Movement Scale (AIMS) From Baseline to Week 12	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.
Percent Change in Total Motor Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using a Mixed Model for Repeated Measures (MMRM)	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.
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	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.
Participants With Adverse Events During the Overall Treatment Period	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.

Trial Locations

Locations (106): Teva Investigational Site 154
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Baltimore, Maryland, United States
Teva Investigational Site 168
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Burlington, Vermont, United States
Teva Investigational Site 160
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Irvine, California, United States
Teva Investigational Site 177
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Imperial, California, United States
Teva Investigational Site 157
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Boca Raton, Florida, United States
Teva Investigational Site 155
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Augusta, Georgia, United States
Teva Investigational Site 113
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Chicago, Illinois, United States
Teva Investigational Site 536
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Bydgoszcz, Poland
Teva Investigational Site 552
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Katowice, Poland
Teva Investigational Site 511
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Lublin, Poland
Teva Investigational Site 524
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Lublin, Poland
Teva Investigational Site 549
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Olsztyn, Poland
Teva Investigational Site 528
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Rimavska Sobota, Slovakia
Teva Investigational Site 153
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Miami, Florida, United States
Teva Investigational Site 110
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San Diego, California, United States
Teva Investigational Site 115
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Salt Lake City, Utah, United States
Teva Investigational Site 145
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Tuscaloosa, Alabama, United States
Teva Investigational Site 162
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Miami, Florida, United States
Teva Investigational Site 121
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Los Angeles, California, United States
Teva Investigational Site 176
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Loma Linda, California, United States
Teva Investigational Site 169
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San Rafael, California, United States
Teva Investigational Site 147
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Los Angeles, California, United States
Teva Investigational Site 165
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Decatur, Georgia, United States
Teva Investigational Site 131
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Chicago, Illinois, United States
Teva Investigational Site 144
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Port Charlotte, Florida, United States
Teva Investigational Site 138
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Asheville, North Carolina, United States
Teva Investigational Site 146
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Raleigh, North Carolina, United States
Teva Investigational Site 149
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Memphis, Tennessee, United States
Teva Investigational Site 559
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Havirov, Czechia
Teva Investigational Site 171
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Charlottesville, Virginia, United States
Teva Investigational Site 531
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Prague 8, Czechia
Teva Investigational Site 502
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Gera, Germany
Teva Investigational Site 166
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Waukesha, Wisconsin, United States
Teva Investigational Site 167
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Richland, Washington, United States
Teva Investigational Site 556
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Hostivice, Czechia
Teva Investigational Site 530
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Prague 6, Czechia
Teva Investigational Site 538
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Budapest, Hungary
Teva Investigational Site 541
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Budapest, Hungary
Teva Investigational Site 546
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Gyor, Hungary
Teva Investigational Site 554
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Bialystok, Poland
Teva Investigational Site 510
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Bydgoszcz, Poland
Teva Investigational Site 517
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Choroszcz, Poland
Teva Investigational Site 513
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Gdansk, Poland
Teva Investigational Site 508
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Lodz, Poland
Teva Investigational Site 521
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Pruszkow, Poland
Teva Investigational Site 522
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Torun, Poland
Teva Investigational Site 555
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Warszawa, Poland
Teva Investigational Site 529
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Bratislava, Slovakia
Teva Investigational Site 175
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Saint Louis, Missouri, United States
Teva Investigational Site 507
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Prien am Chiemsee, Germany
Teva Investigational Site 544
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Taufkirchen, Germany
Teva Investigational Site 545
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Kalocsa, Hungary
Teva Investigational Site 148
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New York, New York, United States
Teva Investigational Site 141
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Salt Lake City, Utah, United States
Teva Investigational Site 107
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Anaheim, California, United States
Teva Investigational Site 108
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Anaheim, California, United States
Teva Investigational Site 123
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Glendale, California, United States
Teva Investigational Site 174
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Norwalk, California, United States
Teva Investigational Site 104
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San Bernardino, California, United States
Teva Investigational Site 170
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Oceanside, California, United States
Teva Investigational Site 156
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Washington, District of Columbia, United States
Teva Investigational Site 150
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Lake City, Florida, United States
Teva Investigational Site 101
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Glen Burnie, Maryland, United States
Teva Investigational Site 161
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Saint Louis, Missouri, United States
Teva Investigational Site 135
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Boston, Massachusetts, United States
Teva Investigational Site 128
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Albuquerque, New Mexico, United States
Teva Investigational Site 178
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Lincoln, Nebraska, United States
Teva Investigational Site 172
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Commack, New York, United States
Teva Investigational Site 558
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Hradec Kralove, Czechia
Teva Investigational Site 535
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Litomerice, Czechia
Teva Investigational Site 557
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Plzen, Czechia
Teva Investigational Site 533
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Praha 10, Czechia
Teva Investigational Site 532
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Praha 5, Czechia
Teva Investigational Site 504
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Mainz, Germany
Teva Investigational Site 503
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Haag In Oberbayern, Germany
Teva Investigational Site 534
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Praha 9, Czechia
Teva Investigational Site 501
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Wolfach, Germany
Teva Investigational Site 537
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Budapest, Hungary
Teva Investigational Site 539
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Doba, Hungary
Teva Investigational Site 547
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Szeged, Hungary
Teva Investigational Site 542
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Budapest, Hungary
Teva Investigational Site 514
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Belchatow, Poland
Teva Investigational Site 523
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Chelmno, Poland
Teva Investigational Site 512
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Katowice, Poland
Teva Investigational Site 509
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Krakow, Poland
Teva Investigational Site 550
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Warszawa, Poland
Teva Investigational Site 516
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Wroclaw, Poland
Teva Investigational Site 525
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Hronovce, Slovakia
Teva Investigational Site 526
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Roznava, Slovakia
Teva Investigational Site 129
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Englewood, Colorado, United States
Teva Investigational Site 106
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Irvine, California, United States
Teva Investigational Site 151
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Fort Worth, Texas, United States
Teva Investigational Site 118
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Creve Coeur, Missouri, United States
Teva Investigational Site 102
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Orange, California, United States
Teva Investigational Site 164
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Kansas City, Kansas, United States
Teva Investigational Site 540
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Balassagyarmat, Hungary
Teva Investigational Site 112
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Orlando, Florida, United States
Teva Investigational Site 139
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New Haven, Connecticut, United States
Teva Investigational Site 142
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Kansas City, Missouri, United States
Teva Investigational Site 133
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Charleston, South Carolina, United States
Teva Investigational Site 519
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Bydgoszcz, Poland
Teva Investigational Site 527
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Kosice, Slovakia
Teva Investigational Site 515
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Lublin, Poland
Teva Investigational Site 520
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Krakow, Poland
Teva Investigational Site 518
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Sosnowiec, Poland
Teva Investigational Site 117
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Gainesville, Florida, United States