Clinical trial NCT02286206: Study of the Effect of Dosing on Clozapine Levels
Official title: A Pilot Study to Determine How Frequency of Administration Modifies Steady-State Plasma Concentrations of Orally Administered Clozapine
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Psychotic Disorders
Schizophrenia
Keywords: Clozapine
Psychotropic Drugs
Antipsychotic Agents
Psychotic Disorders
Schizophrenia
Adverse Effects
Drug Monitoring
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2014-11-07
Enrollment: 0
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Change from baseline in steady-state trough plasma concentrations of clozapine and norclozapine at Days 7 and 14.
timeFrame: Days 0 (baseline), 7, and 14
Secondary outcomes:
measure: Change from baseline in symptoms at Day 14.
timeFrame: Day 0 (baseline) and 14
measure: Change from baseline in side effect burden at Day 14
timeFrame: Days 0 (baseline) and 14
measure: Changes from baseline in laboratory measures at Day 14.
timeFrame: Days 0 (baseline) and 14
measure: Change from baseline in weight and waist circumference at Day 14.
timeFrame: Days 0 (baseline) and 14
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: UBC Hospital - Detwiller Pavilion
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Ric M. Procyshyn, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Alasdair Barr, Ph.D
role: STUDY_DIRECTOR
affiliation: University of British Columbia
name: William Honer, MD
role: STUDY_DIRECTOR
affiliation: University of British Columbia
name: Randall White, MD
role: STUDY_DIRECTOR
References: