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Addressing Involuntary Movements in Tardive Dyskinesia (AIM-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: NCT02291861
Recruitment Status : Completed
First Posted : November 17, 2014
Results First Posted : April 11, 2018
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Auspex Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE November 12, 2014
First Posted Date  ICMJE November 17, 2014
Results First Submitted Date  ICMJE March 15, 2018
Results First Posted Date  ICMJE April 11, 2018
Last Update Posted Date April 2, 2019
Actual Study Start Date  ICMJE October 31, 2014
Actual Primary Completion Date August 19, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 12, 2014)
Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: Baseline and Week 12 ]
Change in AIMS score from Baseline to Week 12.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2014)
Clinical Global Impression of Change (CGIC) [ Time Frame: Week 12 ]
Proportion of subjects who are treatment success based on the CGIC questionnaire.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: November 12, 2014)
  • Exploratory Efficacy Assessment [ Time Frame: Baseline and Week 12 ]
    Quality of Life
  • Exploratory Efficacy Assessment [ Time Frame: Week 12 ]
    Treatment success based on Patient Global Impression of Change (PGIC) questionnaire.
  • Exploratory Efficacy Assessment [ Time Frame: Baseline and Week 12 ]
    Percent reduction in AIMS score
  • Exploratory Efficacy Assessment [ Time Frame: Baseline and Week 12 ]
    Proportion of responders based on AIMS score change from baseline.
 
Descriptive Information
Brief Title  ICMJE Addressing Involuntary Movements in Tardive Dyskinesia
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Tardive Dyskinesia
Intervention  ICMJE
  • 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:
    • deutetrabenzine
    • Austedo
  • Drug: Placebo
    Placebo tablets taken twice daily for 12 weeks. Tablets were swallowed whole with water and taken with food.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo tablets taken twice daily for 12 weeks.
    Intervention: Drug: Placebo
  • Experimental: SD-809 12 mg/day
    SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
    Intervention: Drug: SD-809
  • 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.
    Intervention: Drug: SD-809
  • 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.
    Intervention: Drug: SD-809
Publications * 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 double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Psychiatry. 2017 Aug;4(8):595-604. doi: 10.1016/S2215-0366(17)30236-5. Epub 2017 Jun 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 10, 2017)
298
Original Estimated Enrollment  ICMJE
 (submitted: November 12, 2014)
200
Actual Study Completion Date  ICMJE August 19, 2016
Actual Primary Completion Date August 19, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Germany,   Hungary,   Poland,   Slovakia,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02291861
Other Study ID Numbers  ICMJE SD-809-C-23
2014-003135-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Teva Pharmaceutical Industries ( Auspex Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Auspex Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Teva Medical Expert, MD Teva Pharmaceuticals USA
PRS Account Teva Pharmaceutical Industries
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP