Sarizotan in the Treatment of Neuroleptic-induced Tardive Dyskinesia
TD is a troublesome and potentially irreversible side effect associated with the use of neuroleptics. While the newer neuroleptics are improved in this regard, they all still carry the risk of TD.
The present study proposes that sarizotan is a potential agent for treating neuroleptic-induced TD based on preliminary data indicating efficacy in the management of dyskinesias associated with Parkinson's disease. Its efficacy is further substantiated by pre-clinical data obtained from the vacuous chewing movement (VCM) model in rats, a model we employ ourselves in investigating the relationship between D2 occupancy and TD. The present study also examines the effects of sarizotan on cognitive function, given the association between TD and cognitive deficits.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Dual-centre, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Determine the Effects of Various Adjunctive Doses of Sarizotan in the Treatment of Patients With Neuroleptic-induced Tardive Dyskinesia|
- Degree of change in the Abnormal Involuntary Movement Scale [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
- Change in PANSS [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Change in Simpson-Angus Rating Scales for acute EPS [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
- Change in Barnes Akathisia Rating Scale [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2004|
|Estimated Study Completion Date:||March 2008|
|Primary Completion Date:||September 2006 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Placebo hard gelatin capsules matching the investigational medication
Placebo for each patient randomized to the placebo arm will be given placebo (oral, twice daily) in a pill form for 12 weeks
Other Name: Sugar Pill
Experimental: Sarizotan HCI
Sarizotan HCI is administered at various doses ranging from 2-7mg.
The dose of sariztan HCI for each patient in the drug arm will be given 2mg b.i.d. orally during the first 4 weeks of treatment. If efficacy is inadequate and there are no safety concerns, the option to raise the dose to 5mg b.i.d is given. After 8 weeks of treatment, the option to raise the dose to 7mg bid is given. Dose may remain the same or may be decreased again to the previous dose.
Other Name: Sarizotan HCI
The primary objective of the study is to assess the safety and the anti-dyskinetic properties of sarizotan at various dosages for neuroleptic-induced TD.
The secondary objective of the study is to assess the effects of sarizotan on cognitive function in patients with neuroleptic-induced TD.
The diagnosis of neuroleptic-induced TD will be confirmed by history and physical examination. Patients will be evaluated at baseline, 2, 4, 8, and 12 weeks. Safety will be assessed by vital signs, ECG, routine blood tests, the ACTH stimulation test, and the clinician's and patient's global impression of tolerability.
For efficacy, the primary outcome variable will be changes in the Abnormal Involuntary Movement Scale (AIMS), and a baseline score of >3 ('moderate') will be required for item 8 (Severity of Abnormal Movements). Quantitative evaluation of movements will be carried out in two ways. The first involves a series of instrumental and clinical measures that were developed as a battery for the assessment of antipsychotic-induced parkinsonism and TD. The second means of quantifying the movements involves the use of video recording, with independent evaluation by several raters (Appendix I). Such approaches have gained popularity in the quantification of movement disorders as a means of improving reliability.
Secondary measures will include the positive and negative syndrome scale (PANSS) and other movement disorder scales (Simpson-Angus Rating Scales) for acute extrapyramidal symptoms (EPS), and the Barnes Akathisia Rating Scale (BARS). Global impressions of efficacy and tolerability by the clinician (CGI) and by the patients (PGI) will be recorded at all study visits after the commencement of treatment. To assess potential cognitive changes that may occur in conjunction with TD changes, a battery of neuropsychological tests will be carried out at baseline and endpoint (see Appendix II). To assess the relationship with primary negative symptoms such as the deficit syndrome, the total and sub-scales of the Positive and Negative Syndrome Scale will be evaluated.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00310661
|Centre for Addiction and Mental Health|
|Toronto, Ontario, Canada, M5T 1R8|
|Schizophrenia Research Foundation of India|
|Chennai, India, 600101|
|Principal Investigator:||Gary Remington, MD||Centre for Addiction and Mental Health|