Study of the Effect of Dosing on Clozapine Levels

Schizophrenia Clinical Trial

— PK-CLZ  

Official title:

A Pilot Study to Determine How Frequency of Administration Modifies Steady-State Plasma Concentrations of Orally Administered Clozapine

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02286206
• Other study ID #: H14-01644
• Status: Withdrawn
• Phase: Phase 4
• Start date: January 2015
• Est. completion date: December 2017

Study information

• Verified date: October 2021
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Mental Disorders
• Psychotic Disorders
• Schizophrenia

Intervention

Drug:
• 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)

Locations

Country	Name	City	State
Canada	UBC Hospital - Detwiller Pavilion	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in steady-state trough plasma concentrations of clozapine and norclozapine at Days 7 and 14.	Steady-state trough plasma concentrations of clozapine and norclozapine will be measured on Days 7 and 14 and compared to those obtained on Day 0 (baseline).	Days 0 (baseline), 7, and 14
Secondary	Change from baseline in symptoms at Day 14.	As assessed by structured clinical interviews for the Positive and Negative Syndrome Scale (PANSS)	Day 0 (baseline) and 14
Secondary	Change from baseline in side effect burden at Day 14	As assessed by the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale	Days 0 (baseline) and 14
Secondary	Changes from baseline in laboratory measures at Day 14.	Laboratory measures include fasting blood glucose, fasting lipid profile, creatinine, and urea.	Days 0 (baseline) and 14
Secondary	Change from baseline in weight and waist circumference at Day 14.		Days 0 (baseline) and 14