Study of the Effect of Dosing on Clozapine Levels

NCT ID: NCT02286206

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2017-12-31

Brief Summary

The objectives of this 15-day study are:

1. To compare steady-state trough plasma concentrations of clozapine and its metabolite norclozapine when given once daily and twice daily (at the same total daily dose)

2. To determine if frequency of clozapine administration has an effect on:

1. Symptoms of schizophrenia

2. Adverse effects of clozapine

3. Fasting blood glucose, lipids, creatinine, and urea

4. Weight and waist circumference

Detailed Description

It is important that clinicians do everything possible to optimize the use of clozapine in individuals with treatment-resistant schizophrenia. To our knowledge, there are no published studies evaluating whether twice daily administration of clozapine is better than once daily administration in terms of effectiveness and tolerability. Although this may seem trivial at first, when we consider that clozapine has a relatively short half-life and dissociates quickly from the dopamine D2 receptor, it justifies further consideration. It takes on even more significance knowing that the established threshold clozapine plasma concentration for therapeutic response (i.e., 350-420 ng/ml) was determined using steady-state trough plasma samples (i.e., approximately 12 hours after the evening dose) in patients administered clozapine twice rather than once daily.

Conditions

Psychotic Disorders; Schizophrenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Clozapine bid

Participants have been taking clozapine once daily and have reached steady-state prior to the start of this study.

Intervention: Days 1-14

Group Type: EXPERIMENTAL

Clozapine

Intervention Type: DRUG

One-half baseline dose po bid (or one-third baseline dose po qam and two-thirds baseline dose po qhs at the discretion of the treating clinicians and principal investigator)

Interventions

Clozapine

One-half baseline dose po bid (or one-third baseline dose po qam and two-thirds baseline dose po qhs at the discretion of the treating clinicians and principal investigator)

Intervention Type: DRUG

Other Intervention Names

Clozaril; FazaClo

Eligibility Criteria

Inclusion Criteria

• Participants must be between the ages of 19 - 65
• Participants must be fluent in English
• Participants must have a psychiatric diagnosis and are currently treated with clozapine once daily in the evening
• Participants must be on a stable dose of clozapine for at least one week to ensure steady-state has been achieved

Exclusion Criteria

• Participants who are hypersensitive to clozapine
• Participants who are pregnant or lactating
• Participants who are of childbearing age and not using reliable contraception
• Participants who have postsurgical complications of the gastrointestinal tract that might impair absorption
• Participants who have any clinically relevant abnormalities of laboratory parameters
• Participants who have had a potent CYP1A2 metabolic inducer (e.g., carbamazepine; rifampin) or inhibitor (e.g., amiodarone; cimetidine; efavirenz; fluoroquinolone antibiotics; ticlopidine) added to and/or removed from their medication regimen in the past two weeks

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Ric Procyshyn

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ric M. Procyshyn, Ph.D

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Alasdair Barr, Ph.D

Role: STUDY_DIRECTOR

University of British Columbia

William Honer, MD

Role: STUDY_DIRECTOR

University of British Columbia

Randall White, MD

Role: STUDY_DIRECTOR

University of British Columbia

Locations

UBC Hospital - Detwiller Pavilion

Vancouver, British Columbia, Canada

Countries

Canada

Other Identifiers

H14-01644

Identifier Type: -

Identifier Source: org_study_id