Sarizotan in the Treatment of Neuroleptic-induced Tardive Dyskinesia

• Status: Terminated
• Trial end date: 2008-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre for Addiction and Mental Health
• Collaborators: Merck KGaA; Merck KGaA, Darmstadt, Germany
• Treatments: Antipsychotic Agents

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.