NCT00310661

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Dec 2004

Longer than P75 for not_applicable

Geographic Reach
2 countries

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2004

Completed
1.3 years until next milestone

First Submitted

Initial submission to the registry

April 3, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 4, 2006

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2006

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2008

Completed
Last Updated

July 23, 2015

Status Verified

July 1, 2015

Enrollment Period

1.8 years

First QC Date

April 3, 2006

Last Update Submit

July 22, 2015

Conditions

Neuroleptic-induced Tardive Dyskinesia

Keywords

sarizotanneuroleptic-induced tardive dyskinesia

Outcome Measures

Primary Outcomes (1)

  • Degree of change in the Abnormal Involuntary Movement Scale

    12 weeks

Secondary Outcomes (3)

  • Change in PANSS

    12 weeks

  • Change in Simpson-Angus Rating Scales for acute EPS

    12 weeks

  • Change in Barnes Akathisia Rating Scale

    12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo hard gelatin capsules matching the investigational medication

Other: Placebo

Sarizotan HCI

EXPERIMENTAL

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

Drug: Sarizotan

Interventions

SarizotanDRUG

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.

Also known as: Sarizotan HCI
Sarizotan HCI
PlaceboOTHER

Placebo for each patient randomized to the placebo arm will be given placebo (oral, twice daily) in a pill form for 12 weeks

Also known as: Sugar Pill
Placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • Lack of legal capacity, or limited legal capacity.)
  • Known previous diagnosis of learning disability.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

Schizophrenia Research Foundation of India

Chennai, 600101, India

Location

Related Publications (1)

  • 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.

    PMID: 15996562BACKGROUND

Related Links

MeSH Terms

Interventions

sarizotanSugars

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

  • Gary Remington, MD

    Centre for Addiction and Mental Health

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

April 3, 2006

First Posted

April 4, 2006

Study Start

December 1, 2004

Primary Completion

September 1, 2006

Study Completion

March 1, 2008

Last Updated

July 23, 2015

Record last verified: 2015-07

Locations

CA(1)IN(1)