Addressing Involuntary Movements in Tardive Dyskinesia

Tardive Dyskinesia Clinical Trial

— AIM-TD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02291861
• Other study ID #: SD-809-C-23
• Secondary ID: 2014-003135-19
• Status: Completed
• Phase: Phase 3
• Start date: October 31, 2014
• Est. completion date: August 19, 2016

Study information

• Verified date: November 2021
• 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 determine whether fixed-doses of an investigational drug, SD-809 (deutetrabenazine), will reduce the severity of abnormal involuntary movements of tardive dyskinesia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 298
• Est. completion date: August 19, 2016
• Est. primary completion date: August 19, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

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

• 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

Related Conditions & MeSH terms

• Dyskinesias
• Tardive Dyskinesia

Intervention

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.
• Placebo
Placebo tablets taken twice daily for 12 weeks. Tablets were swallowed whole with water and taken with food.

Locations

Country	Name	City	State
Czechia	Teva Investigational Site 559	Havirov
Czechia	Teva Investigational Site 556	Hostivice
Czechia	Teva Investigational Site 558	Hradec Kralove
Czechia	Teva Investigational Site 535	Litomerice
Czechia	Teva Investigational Site 557	Plzen
Czechia	Teva Investigational Site 530	Prague 6
Czechia	Teva Investigational Site 531	Prague 8
Czechia	Teva Investigational Site 533	Praha 10
Czechia	Teva Investigational Site 532	Praha 5
Czechia	Teva Investigational Site 534	Praha 9
Germany	Teva Investigational Site 502	Gera
Germany	Teva Investigational Site 503	Haag In Oberbayern
Germany	Teva Investigational Site 504	Mainz
Germany	Teva Investigational Site 507	Prien am Chiemsee
Germany	Teva Investigational Site 544	Taufkirchen
Germany	Teva Investigational Site 501	Wolfach
Hungary	Teva Investigational Site 540	Balassagyarmat
Hungary	Teva Investigational Site 537	Budapest
Hungary	Teva Investigational Site 538	Budapest
Hungary	Teva Investigational Site 541	Budapest
Hungary	Teva Investigational Site 542	Budapest
Hungary	Teva Investigational Site 539	Doba
Hungary	Teva Investigational Site 546	Gyor
Hungary	Teva Investigational Site 545	Kalocsa
Hungary	Teva Investigational Site 547	Szeged
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 515	Lublin
Poland	Teva Investigational Site 524	Lublin
Poland	Teva Investigational Site 549	Olsztyn
Poland	Teva Investigational Site 521	Pruszkow
Poland	Teva Investigational Site 518	Sosnowiec
Poland	Teva Investigational Site 522	Torun
Poland	Teva Investigational Site 550	Warszawa
Poland	Teva Investigational Site 555	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 138	Asheville	North Carolina
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 135	Boston	Massachusetts
United States	Teva Investigational Site 168	Burlington	Vermont
United States	Teva Investigational Site 133	Charleston	South Carolina
United States	Teva Investigational Site 171	Charlottesville	Virginia
United States	Teva Investigational Site 113	Chicago	Illinois
United States	Teva Investigational Site 131	Chicago	Illinois
United States	Teva Investigational Site 172	Commack	New York
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 101	Glen Burnie	Maryland
United States	Teva Investigational Site 123	Glendale	California
United States	Teva Investigational Site 177	Imperial	California
United States	Teva Investigational Site 106	Irvine	California
United States	Teva Investigational Site 160	Irvine	California
United States	Teva Investigational Site 142	Kansas City	Missouri
United States	Teva Investigational Site 164	Kansas City	Kansas
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 148	New York	New York
United States	Teva Investigational Site 174	Norwalk	California
United States	Teva Investigational Site 170	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, 

References & Publications (1)

Anderson KE, Stamler D, Davis MD, Factor SA, Hauser RA, Isojärvi J, Jarskog LF, Jimenez-Shahed J, Kumar R, McEvoy JP, Ochudlo S, Ondo WG, Fernandez HH. Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a — View Citation

Outcome

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