ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Auspex Pharmaceuticals, Inc. )

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Tardive Dyskinesia
Interventions: Drug: SD-809
Drug: Placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was performed at 75 study centers (38 in the US, 19 in Poland, 7 in Hungary, 6 in the Czech Republic, 3 in Slovakia, and 2 in Germany) by 75 investigators; 298 patients were enrolled.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomly assigned in a 1:1:1:1 ratio to receive 1 of 3 fixed-dose regimens of SD-809 (deutetrabenazine) or placebo following a screening period.

Reporting Groups
  Description
Placebo Placebo tablets taken twice daily for 12 weeks.
SD-809 12 mg/Day SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
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.
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.

Participant Flow:   Overall Study
    Placebo   SD-809 12 mg/Day   SD-809 24 mg/Day   SD-809 36 mg/Day
STARTED   74   75   74   75 
Safety Population   72   74   73   74 
Modified Intent to Treat Pop (mITT)   58   60   49   55 
COMPLETED   67   67   65   65 
NOT COMPLETED   7   8   9   10 
Adverse Event                2                4                1                2 
Death                0                0                1                1 
Protocol Violation                1                0                0                1 
Withdrawal by Subject                1                2                1                4 
Noncompliance                1                1                2                1 
Lost to Follow-up                2                1                4                0 
Not specified                0                0                0                1 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Population was a subset of randomized participants and included all patients who were administered study drug (N=293).

Reporting Groups
  Description
Placebo Placebo tablets taken twice daily for 12 weeks.
SD-809 12 mg/Day SD-809 tablets 6 mg taken twice a day (BID) for 12 weeks.
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.
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.
Total Total of all reporting groups

Baseline Measures
   Placebo   SD-809 12 mg/Day   SD-809 24 mg/Day   SD-809 36 mg/Day   Total 
Overall Participants Analyzed 
[Units: Participants]
 72   74   73   74   293 
Age 
[Units: Years]
Mean (Standard Deviation)
         
Participants Analyzed   72   74   73   74   293 
   54.6  (12.06)   57.0  (9.95)   55.6  (11.34)   58.3  (11.55)   56.4  (11.27) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Participants Analyzed   72   74   73   74   293 
Female   37   42   41   42   162 
Male   35   32   32   32   131 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
         
Participants Analyzed   72   74   73   74   293 
American Indian or Alaska Native   1   1   0   2   4 
Asian   0   0   0   0   0 
Black or African American   12   15   19   10   56 
Native Hawaiian or Pacific Islander   0   0   0   0   0 
White   59   58   54   61   232 
Other   0   0   0   1   1 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
         
Participants Analyzed   72   74   73   74   293 
Hispanic or latino   7   6   3   7   23 
Not hispanic or latino   64   64   69   65   262 
Not reported   0   3   1   1   5 
Unknown   1   1   0   1   3 
Weight 
[Units: Kg]
Mean (Standard Deviation)
         
Participants Analyzed   72   74   73   74   293 
   82.8  (18.51)   80.8  (21.00)   86.8  (18.79)   78.5  (17.56)   82.2  (19.16) 
Height 
[Units: Cm]
Mean (Standard Deviation)
         
Participants Analyzed   72   74   73   74   293 
   168.3  (9.25)   167.7  (10.68)   168.7  (9.39)   167.6  (10.55)   168.1  (9.96) 
Body Mass Index 
[Units: Kg/m^2]
Mean (Standard Deviation)
         
Participants Analyzed   72   74   73   74   293 
   29.18  (6.128)   28.69  (6.814)   30.64  (7.021)   27.99  (6.178)   29.12  (6.587) 
Education Level 
[Units: Participants]
Count of Participants
         
Participants Analyzed   72   74   73   74   293 
<= 12 years   40   44   44   39   167 
> 12 years   32   30   29   35   126 
Time Since Tardive Dyskinesia (TD) Diagnosis 
[Units: Years]
Mean (Standard Deviation)
         
Participants Analyzed   72   74   73   74   293 
   6.03  (5.353)   5.49  (5.426)   4.98  (6.034)   5.89  (5.342)   5.60  (5.532) 
Total Motor Abnormal Involuntary Movement Scale (AIMS) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
         
Participants Analyzed   72   74   73   74   293 
   8.5  (3.28)   8.6  (3.13)   7.7  (3.51)   8.6  (3.84)   8.4  (3.46) 
[1]

The 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.

Total Motor assessment sums items 1 through 7 which cover orofacial movements, as well as extremity and truncal dyskinesia. 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.

Modified Craniocervical Dystonia Questionnaire (mCDQ-24) [1] [2] 
[Units: Units on a scale]
Mean (Standard Deviation)
         
Participants Analyzed   72   73   73   74   292 
   40.5  (19.88)   37.2  (20.15)   34.4  (19.59)   34.9  (18.34)   36.7  (19.55) 
[1] 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. Each of the 24 questions was rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 – 96.
[2] One participant in the SD-809 12 mg/day group was missing a baseline mCDQ-24 total score.
Baseline Use of a Dopamine Receptor Antagonist (DRA) [1] 
[Units: Participants]
Count of Participants
         
Participants Analyzed   72   74   73   74   293 
Yes   56   56   57   53   222 
No   16   18   16   21   71 
[1] The randomization was stratified by baseline use of DRA (currently taking versus not currently taking a DRA).


  Outcome Measures

1.  Primary:   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 ]

2.  Secondary:   Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)   [ Time Frame: Week 12 ]

3.  Secondary:   Change in the Modified Craniocervical Dystonia Questionnaire (mCDQ-24) Total Score From Baseline to Week 12   [ Time Frame: Day 0 (Baseline), Week 12 ]

4.  Secondary:   Percentage of Patients Considered a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)   [ Time Frame: Week 12 ]

5.  Secondary:   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 ]

6.  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)   [ Time Frame: Day 0 (Baseline), Weeks 2, 4, 8 and 12 ]

7.  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   [ Time Frame: Day 0 (Baseline), Week 12 ]

8.  Secondary:   Participants With Adverse Events During the Overall Treatment Period   [ Time Frame: Day 1 to Week 12 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc
phone: 215-591-3000
e-mail: ustevatrials@tevapharm.com


Publications of Results:

Responsible Party: Teva Pharmaceutical Industries ( Auspex Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02291861     History of Changes
Other Study ID Numbers: SD-809-C-23
2014-003135-19 ( EudraCT Number )
First Submitted: November 12, 2014
First Posted: November 17, 2014
Results First Submitted: March 15, 2018
Results First Posted: April 11, 2018
Last Update Posted: May 14, 2018