A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF SD-809 (DEUTETRABENAZINE) FOR THE TREATMENT OF MODERATE TO SEVERE TARDIVE DYSKINESIA
- Conditions
- Tardive DyskinesiaTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2014-001890-15-PL
- Lead Sponsor
- Auspex Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 92
1. Subject is between 18 and 75 years of age, inclusive.
2. Subject has a history of using a dopamine receptor antagonist for at least 3 months
(or 1 month in subjects 60 years of age and older).
3. Subject has a clinical diagnosis of TD, and has had symptoms for at least 3
months prior to Screening.
4. The subject’s TD symptoms are bothersome to the subject or cause functional
impairment.
5. At the Screening and Baseline visits, the subject has:
• Moderate or severe abnormal movements as judged by the Investigator based
on Item 8 of the AIMS (see Appendix 2), AND
• A total motor AIMS score of =6 (based on Items 1 through 7) as assessed by
the Principal Investigator. Note: A video recording of the AIMS assessment
at Screening will be reviewed by a blinded central rater to confirm eligibility
prior to randomization.
6. For subjects with underlying psychiatric illness:
• Subject is psychiatrically stable and has had no change in psychoactive
medications (including, but not limited to neuroleptics, benzodiazepines,
anticonvulsants, and mood stabilizers) for =30 days before Screening (45 days
for antidepressants).
• Subjects on long-acting (depot) medications have been on stable therapy
(dose, frequency) for =3 months before Screening.
• Subject has a mental health provider who is aware of the subject’s
participation in the trial, and does not anticipate any changes to the subject’s treatment regimen (drug, dose, frequency) in the next 3 months.
7. Subject has a history of being compliant with prescribed medications.
8. Subject is able to swallow study drug whole.
9. Subject has provided written, informed consent or, if subject lacks the capacity to
provide informed consent, a legally authorized representative (LAR) has provided
written informed consent and the subject has provided assent.
10. In the opinion of the Investigator, the subject lives in a stable environment, and
has adequate supervision when necessary to comply with all study procedures,
attend all study visits and safely participate in the trial.
11. Subject is in good general health, is expected to attend all study visits and is
expected to complete all study assessments, in the opinion of the Investigator.
12. Subject has sufficient reading skills to comprehend the subject-completed rating
scales.
13. Female subjects of childbearing potentiala agree to use one of the following
acceptable methods of contraception from Screening through study completion if
sexually active:
• IUD or intrauterine system in place for at least 3 months prior to screening;
• Subject or partner using barrier method (e.g., condom, diaphragm, or cervical
cap) with spermicide from Screening through study completion;
• Partner has a documented vasectomy >6 months prior to enrollment.
• Stable hormonal contraception (with approved oral, transdermal, or depot
regimen) for at least 3 months prior to Screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 73
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 19
1. Subject has received any of the following medications within 30 days of
Screening or Baseline:
• Tetrabenazine, reserpine, a-methyl-p-tyrosine (AMPT), botulinum toxin
(within 3 months of Screening), and medications with strong anticholinergic
activity (trihexyphenidyl, benztropine, orphenadrine, procyclidine, and
biperiden)
• Metoclopramide, promethazine, and prochlorperazine
• Stimulants (i.e., methylphenidate, amphetamine/dextroamphetamine,
lisdexamphetamine, etc.), or monoamine oxidase inhibitors (MAOIs)
• Levodopa or dopamine agonists
2. Subject has participated in any previous study of SD-809 in which they received
SD-809.
3. Subject has a neurological condition other than TD that may interfere with
assessing the severity of dyskinesias.
4. Subject has a serious untreated or undertreated psychiatric illness at Screening or
Baseline.
5. Subject has active suicidal ideation at Screening or Baseline.
6. Subject has history of any of the following within 6 months of Screening:
• Previous intent to act on suicidal ideation with a specific plan (positive answer
to question 5 on C-SSRS), irrespective of level of ambivalence at the time of
suicidal thought
• Previous preparatory acts to commit suicide or suicidal behavior
• A previous actual, interrupted or aborted suicide attempt 7. Subject has a score =11 on the depression subscale of the Hospital Anxiety and
Depression Scale (HADS) at Screening or Baseline.
8. Subject is developmentally disabled or has evidence of dementia.
9. Subject has an unstable or serious medical illness at Screening or Baseline.
10. Subject has history (within 3 months) or presence of violent behavior.
11. Subject has a QTcF value >450 ms (males) or >460 ms (females), or >480 ms
(with right bundle branch block [RBBB]) on 12-lead ECG at Screening.
12. Subject has evidence of hepatic impairment at Screening, as indicated by:
• Aspartate transaminase (AST) or alanine aminotransferase (ALT) >2.5 times
the upper limit of normal (ULN).
• Alkaline phosphatase (ALP) or total bilirubin (TBil) >2 times the ULN
o Note: Subjects with Gilbert’s Syndrome are eligible to participate if
approved by the Medical Monitor.
o Note: Subjects with abnormalities in two or more of these analytes (AST,
ALT, ALP, TBil) must be approved by the Medical Monitor to be
enrolled.
• Prothrombin time >4 seconds prolonged.
• Positive Hepatitis B surface antigen (HBsAg).
13. Subject has evidence of significant renal impairment at Screening, indicated by a
creatinine clearance <50 mL/min, as estimated by the Cockroft-Gault formula.
14. Subject has known allergy to tetrabenazine or to any of the components of
SD-809.
15. Subject has participated in an investigational drug or device trial and received
study drug within 30 days (or 5 drug half-lives) of Screening, whichever is longer.
16. Subject is pregnant or breast-feeding at Screening or Baseline.
17. Subject acknowledges present use of illicit drugs at Screening.
18. Subject has a history of alcohol or substance abuse in the previous 12 months, as
defined in the DSM-V, or subject is unable to refrain from substance abuse
throughout the study.
19. Subject has a positive urine drug screen (for amphetamines, barbiturates,
benzodiazepine, phencyclidine, cocaine, or opiates) at Screening or Baseline,
except if subject is receiving a stable dose of a benzodiazepine.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To evaluate the efficacy of SD-809 to reduce the severity of abnormal involuntary movements of Tardive Dyskinesia<br>• To evaluate the safety and tolerability of titration and maintenance therapy with SD-809 in subjects with drug-induced Tardive Dyskinesia;Secondary Objective: Not applicable;Primary end point(s): The change in AIMS score (Items 1 through 7) from Baseline to Week 12, as assessed by blinded central video rating. The Baseline AIMS score is defined for each subject as the Day 0 assessment.;Timepoint(s) of evaluation of this end point: 12 weeks
- Secondary Outcome Measures
Name Time Method