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Sarizotan in the Treatment of Neuroleptic-induced Tardive Dyskinesia

Primary Purpose

Neuroleptic-induced Tardive Dyskinesia

Status
Terminated
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Sarizotan
Placebo
Sponsored by
Centre for Addiction and Mental Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroleptic-induced Tardive Dyskinesia focused on measuring sarizotan, neuroleptic-induced tardive dyskinesia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The patient meets the Schooler and Kane Diagnostic Criteria (25) for Tardive Dyskinesia as established by history and physical examination. a score of 3 or above for item 8 of the AIMS scale (Severity of Abnormal Movements) at baseline. For female patients: either the patient is surgically sterile, has been post-menopausal for at least 12 months, or she is using a reliable method of contraception (single-barrier methods alone will not be considered sufficiently reliable) and provides a negative pregnancy test at the screening visit. on a stable dose of his/her current antipsychotic (either typical or atypical) and movement disorder medication (e.g. anticholinergics) for at least one month before randomisation. For depot antipsychotics, this period will be at least one dosing interval. The patient gives full written informed consent for participation in the study. The patient has a level of understanding of English or Tamil sufficient to communicate effectively with the investigator and study staff, and to be able to complete the computerised neurocognitive test battery where necessary Exclusion Criteria: Exclusion criteria listed in the Research Criteria for Tardive Dyskinesia as defined in DSM-IV (symptoms not due to another neurological or general medical condition such as Huntington's disease, Sydenham's chorea, spontaneous dyskinesia, hyperthyroidism, Wilson's disease, ill-fitting dentures, exposure to other medications causing acute reversible dyskinesia such as L?dopa or bromocriptine). Evidence of pre-existing tic disorders, neuroleptic-induced acute dystonia or neuroleptic-induced acute akathisia Risk of suicide (in the opinion of the investigator). Any of the following non-permitted concomitant medication: Metoclopramide in the 4 weeks before screening, Buspirone in the 4 weeks before screening, Azole antifungals (particularly ketoconazole), Etomidate, HIV proteinase inhibitors (e.g. indinavir, ritonavir), any tricyclic antidepressant in the 4 weeks before screening (SSRI antidepressants if at a stable dosage are permitted), Fludrocortisone, Intermittent therapy with oral corticoids, continuous therapy with <7.5mg/day (oral) prednisolone or an equivalent dose of a different corticoid (patients on continuous long-term therapy with a dose of >7.5mg prednisolone or equivalent may participate but should not undergo an ACTH challenge test). Treatment with electroconvulsive therapy within six months before the first study visit. Known history of drug dependence (except nicotine and caffeine) or alcohol dependence within the six months before the study (three months for known drug abuse). Evidence of any clinically significant endocrine, cardiac, renal, neurological, cerebrovascular, metabolic, gastrointestinal, immunological, allergic or respiratory disease. Patients who are not euthyroid. asthma or known hypersensitivity to antipsychotic drugs or ACTH Pregnancy or lactation. Any abnormal laboratory test result(s) of potential clinical significance at screening, including: Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) greater than 3 ´ upper limit of normal (ULN), Creatinine >2 ´ ULN, total bilirubin >2 ´ ULN Participation in another clinical study within the 30 days before the first visit of the present study. Plasma cortisol concentration below 18 µg/dL 60 minutes after stimulation with 250 µg ACTH1-24 (for procedure see Section 7.9). (NOTE: This exclusion criterion is waived, and the test should not be carried out, for patients on continuous long-term therapy with a dose of >7.5mg prednisolone or equivalent. Lack of legal capacity, or limited legal capacity.) Known previous diagnosis of learning disability.

Sites / Locations

  • Centre for Addiction and Mental Health
  • Schizophrenia Research Foundation of India

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Sarizotan HCI

Arm Description

Placebo hard gelatin capsules matching the investigational medication

Sarizotan HCI is administered at various doses ranging from 2-7mg.

Outcomes

Primary Outcome Measures

Degree of change in the Abnormal Involuntary Movement Scale

Secondary Outcome Measures

Change in PANSS
Change in Simpson-Angus Rating Scales for acute EPS
Change in Barnes Akathisia Rating Scale

Full Information

First Posted
April 3, 2006
Last Updated
July 22, 2015
Sponsor
Centre for Addiction and Mental Health
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT00310661
Brief Title
Sarizotan in the Treatment of Neuroleptic-induced Tardive Dyskinesia
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Terminated
Why Stopped
Funding
Study Start Date
December 2004 (undefined)
Primary Completion Date
September 2006 (Actual)
Study Completion Date
March 2008 (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre for Addiction and Mental Health
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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. Procedures: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroleptic-induced Tardive Dyskinesia
Keywords
sarizotan, neuroleptic-induced tardive dyskinesia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo hard gelatin capsules matching the investigational medication
Arm Title
Sarizotan HCI
Arm Type
Experimental
Arm Description
Sarizotan HCI is administered at various doses ranging from 2-7mg.
Intervention Type
Drug
Intervention Name(s)
Sarizotan
Other Intervention Name(s)
Sarizotan HCI
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar Pill
Intervention Description
Placebo for each patient randomized to the placebo arm will be given placebo (oral, twice daily) in a pill form for 12 weeks
Primary Outcome Measure Information:
Title
Degree of change in the Abnormal Involuntary Movement Scale
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Change in PANSS
Time Frame
12 weeks
Title
Change in Simpson-Angus Rating Scales for acute EPS
Time Frame
12 weeks
Title
Change in Barnes Akathisia Rating Scale
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The patient meets the Schooler and Kane Diagnostic Criteria (25) for Tardive Dyskinesia as established by history and physical examination. a score of 3 or above for item 8 of the AIMS scale (Severity of Abnormal Movements) at baseline. For female patients: either the patient is surgically sterile, has been post-menopausal for at least 12 months, or she is using a reliable method of contraception (single-barrier methods alone will not be considered sufficiently reliable) and provides a negative pregnancy test at the screening visit. on a stable dose of his/her current antipsychotic (either typical or atypical) and movement disorder medication (e.g. anticholinergics) for at least one month before randomisation. For depot antipsychotics, this period will be at least one dosing interval. The patient gives full written informed consent for participation in the study. The patient has a level of understanding of English or Tamil sufficient to communicate effectively with the investigator and study staff, and to be able to complete the computerised neurocognitive test battery where necessary Exclusion Criteria: Exclusion criteria listed in the Research Criteria for Tardive Dyskinesia as defined in DSM-IV (symptoms not due to another neurological or general medical condition such as Huntington's disease, Sydenham's chorea, spontaneous dyskinesia, hyperthyroidism, Wilson's disease, ill-fitting dentures, exposure to other medications causing acute reversible dyskinesia such as L?dopa or bromocriptine). Evidence of pre-existing tic disorders, neuroleptic-induced acute dystonia or neuroleptic-induced acute akathisia Risk of suicide (in the opinion of the investigator). Any of the following non-permitted concomitant medication: Metoclopramide in the 4 weeks before screening, Buspirone in the 4 weeks before screening, Azole antifungals (particularly ketoconazole), Etomidate, HIV proteinase inhibitors (e.g. indinavir, ritonavir), any tricyclic antidepressant in the 4 weeks before screening (SSRI antidepressants if at a stable dosage are permitted), Fludrocortisone, Intermittent therapy with oral corticoids, continuous therapy with <7.5mg/day (oral) prednisolone or an equivalent dose of a different corticoid (patients on continuous long-term therapy with a dose of >7.5mg prednisolone or equivalent may participate but should not undergo an ACTH challenge test). Treatment with electroconvulsive therapy within six months before the first study visit. Known history of drug dependence (except nicotine and caffeine) or alcohol dependence within the six months before the study (three months for known drug abuse). Evidence of any clinically significant endocrine, cardiac, renal, neurological, cerebrovascular, metabolic, gastrointestinal, immunological, allergic or respiratory disease. Patients who are not euthyroid. asthma or known hypersensitivity to antipsychotic drugs or ACTH Pregnancy or lactation. Any abnormal laboratory test result(s) of potential clinical significance at screening, including: Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) greater than 3 ´ upper limit of normal (ULN), Creatinine >2 ´ ULN, total bilirubin >2 ´ ULN Participation in another clinical study within the 30 days before the first visit of the present study. Plasma cortisol concentration below 18 µg/dL 60 minutes after stimulation with 250 µg ACTH1-24 (for procedure see Section 7.9). (NOTE: This exclusion criterion is waived, and the test should not be carried out, for patients on continuous long-term therapy with a dose of >7.5mg prednisolone or equivalent. Lack of legal capacity, or limited legal capacity.) Known previous diagnosis of learning disability.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Remington, MD
Organizational Affiliation
Centre for Addiction and Mental Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 1R8
Country
Canada
Facility Name
Schizophrenia Research Foundation of India
City
Chennai
ZIP/Postal Code
600101
Country
India

12. IPD Sharing Statement

Citations:
PubMed Identifier
15996562
Citation
Kleven MS, Barret-Grevoz C, Bruins Slot L, Newman-Tancredi A. Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats. Neuropharmacology. 2005 Aug;49(2):135-43. doi: 10.1016/j.neuropharm.2005.02.005. Epub 2005 Apr 1.
Results Reference
background
Links:
URL
http://camh.net
Description
CAMH web site

Learn more about this trial

Sarizotan in the Treatment of Neuroleptic-induced Tardive Dyskinesia

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