Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia

NCT00158223 | Completed Phase 4 Results DMC

• 2 other identifiers: GCO 02-0517R01MH067806
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 3

Brief Summary

This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.

Conditions

Schizophrenia; Psychotic Disorders

Keywords

Schizophrenia; Clozapine; Treatment; Combination; Unresponsive; Schizoaffective Disorders

Outcome Measures

Primary Outcomes (2)

• Positive Syndrome Scale (PANSS) Total Score

  Severity of positive schizophrenic symptoms The Positive Syndrome Scale of the PANSS is comprised of seven items measuring positive such symptoms such as hallucinations, delusions, grandiosity, etc. Each item is scored on a 7 point scale of that particular symptom's severity, ranging from 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate severe, 6 = severe, and 7 = extreme. The PANSS Positive Subscale seven items has a range of a summed score from 7 (absent) to 49 (extreme psychopathology). Therefore, the higher the score, the more severe the symtpoms.

  Variable change from baseline to week 12

• Negative Syndrome Scale (PANSS) Total Score

  Severity of negative schizophrenic symptoms, The Negative Syndrome scale is compromised of seven items, each scored on severity with numeric assignments ranging from 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate severe, 6 = severe, and 7 = extreme. The items which comprise the Negative Syndrome Scale of the PANSS measure things such as emotional withdrawal, apathy, difficulty in abstract thinking, etc. The seven items which comprise the PANSS Negative Subscale has an aggregate range of 7 (absent) to 49 (extreme psychopathology), a higher score indicating more severe symptoms.

  Variable change from baseline to week 12

Secondary Outcomes (1)

• Clinical Global Impression of Change (CGIC)

  variable change from baseline to week 12

Study Arms (2)

placebo

PLACEBO COMPARATOR

Participants will receive encapsulated placebo made to match active drug

Drug: Placebo

pimozide

EXPERIMENTAL

Participants will receive pimozide flexible dosing

Drug: Pimozide

Interventions

Pimozide DRUG

Each capsule of active treatment will contain 2 mg of pimozide. Dosing will be flexible and will range from a minimum of 2 mg per day to 8 mg per day. Dosing will begin at Week 1 with 1 capsule per day. This will be slowly titrated at a rate of 1 capsule per week to a maximum of 4 capsules depending upon clinical response and side effects.

Also known as: Orap

pimozide

Placebo DRUG

Active drug and placebo will be encapsulated in an identical fashion. The placebo capsule will be made to match in appearance and weight. There will be flexible dosing, allowing a minimum of 1 capsule per day to 4 capsules per day, in order to match the dosing range of the active treatment.

Also known as: Sugar Pill

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of schizophrenia according to DSM-IV criteria
• Any schizoaffective disorder or subtype
• Score greater than 60 on the Positive and Negative Syndrome Scale (PANSS)
• Currently taking clozapine
• Score of four or higher on two or more items from the positive symptom subscale of the PANSS
• Score of 4 or greater on the Clinical Global Impression (CGI) scale
• Clozapine plasma level greater than 378 µg/ml
• Stable dose of clozapine demonstrated to have been associated with a clozapine plasma level greater than 378 µg/ml for at least eight weeks
• Able to read at an 8th grade level or above

You may not qualify if:

• History of unstable coronary artery disease
• Congestive heart failure
• History of long Q-T syndrome
• History of cardiac arrhythmia
• History of cardiac conduction delay
• Baseline QT correction score greater than 0.425 seconds
• Liver disease
• History of stroke
• History of Neuroleptic Malignant Syndrome
• Hypokalemia
• Hypocalcemia
• Current blindness, deafness, language difficulties, or any other disability which may prevent participation or cooperation in the study
• Current suicidal or homicidal thoughts
• Currently abusing psychoactive substances

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (3)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Manhattan Psychiatric Center

New York, New York, 10035, United States

Location

Pilgrim Psychiatric Center

W. Brentwood, New York, 11717, United States

Location

Related Publications (2)

• Friedman J, Ault K, Powchik P. Pimozide augmentation for the treatment of schizophrenic patients who are partial responders to clozapine. Biol Psychiatry. 1997 Sep 15;42(6):522-3. doi: 10.1016/S0006-3223(97)00227-8. No abstract available.

  PMID: 9285089 BACKGROUND

• Friedman JI, Lindenmayer JP, Alcantara F, Bowler S, Parak M, White L, Iskander A, Parrella M, Adler DN, Tsopelas ND, Tsai WY, Novakovic V, Harvey PD, Davis KL, Kaushik S. Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy. Neuropsychopharmacology. 2011 May;36(6):1289-95. doi: 10.1038/npp.2011.14. Epub 2011 Feb 23.

  PMID: 21346734 RESULT

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Pimozide; Sugars

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbohydrates

Limitations and Caveats

Neither baseline nor follow-up clozapine plasma concentrations were reported. Possible that one or both groups did not have therapeutic baseline clozapine levels and/or had pharmacokinetic interactions with the study drug changing concentrations.

Results Point of Contact

• Title: Dr. Joseph I. Friedman
• Organization: Icahn School of Medicine at Mount Sinai

joseph.friedman@mssm.edu

631-761-3607

Study Officials

• Joseph I. Friedman, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• 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: Associate Professor

Study Record Dates

• First Submitted: September 7, 2005
• First Posted: September 12, 2005
• Study Start: October 1, 2004
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: April 9, 2015
• Results First Posted: April 9, 2015

Record last verified: 2015-04

Locations

US (3)