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Study of the Effect of Dosing on Clozapine Levels (PK-CLZ)

Primary Purpose

Psychotic Disorders, Schizophrenia

Status
Withdrawn
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Clozapine
Sponsored by
University of British Columbia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Psychotic Disorders focused on measuring Clozapine, Psychotropic Drugs, Antipsychotic Agents, Psychotic Disorders, Schizophrenia, Adverse Effects, Drug Monitoring

Eligibility Criteria

19 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UBC Hospital - Detwiller Pavilion

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Clozapine bid

Arm Description

Participants have been taking clozapine once daily and have reached steady-state prior to the start of this study. Intervention: Days 1-14

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Change from baseline in symptoms at Day 14.
As assessed by structured clinical interviews for the Positive and Negative Syndrome Scale (PANSS)
Change from baseline in side effect burden at Day 14
As assessed by the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale
Changes from baseline in laboratory measures at Day 14.
Laboratory measures include fasting blood glucose, fasting lipid profile, creatinine, and urea.
Change from baseline in weight and waist circumference at Day 14.

Full Information

First Posted
November 4, 2014
Last Updated
October 1, 2021
Sponsor
University of British Columbia
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1. Study Identification

Unique Protocol Identification Number
NCT02286206
Brief Title
Study of the Effect of Dosing on Clozapine Levels
Acronym
PK-CLZ
Official Title
A Pilot Study to Determine How Frequency of Administration Modifies Steady-State Plasma Concentrations of Orally Administered Clozapine
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Withdrawn
Study Start Date
January 2015 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
December 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The objectives of this 15-day study are: 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) To determine if frequency of clozapine administration has an effect on: Symptoms of schizophrenia Adverse effects of clozapine Fasting blood glucose, lipids, creatinine, and urea 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psychotic Disorders, Schizophrenia
Keywords
Clozapine, Psychotropic Drugs, Antipsychotic Agents, Psychotic Disorders, Schizophrenia, Adverse Effects, Drug Monitoring

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Clozapine bid
Arm Type
Experimental
Arm Description
Participants have been taking clozapine once daily and have reached steady-state prior to the start of this study. Intervention: Days 1-14
Intervention Type
Drug
Intervention Name(s)
Clozapine
Other Intervention Name(s)
Clozaril, FazaClo
Intervention Description
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)
Primary Outcome Measure Information:
Title
Change from baseline in steady-state trough plasma concentrations of clozapine and norclozapine at Days 7 and 14.
Description
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).
Time Frame
Days 0 (baseline), 7, and 14
Secondary Outcome Measure Information:
Title
Change from baseline in symptoms at Day 14.
Description
As assessed by structured clinical interviews for the Positive and Negative Syndrome Scale (PANSS)
Time Frame
Day 0 (baseline) and 14
Title
Change from baseline in side effect burden at Day 14
Description
As assessed by the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale
Time Frame
Days 0 (baseline) and 14
Title
Changes from baseline in laboratory measures at Day 14.
Description
Laboratory measures include fasting blood glucose, fasting lipid profile, creatinine, and urea.
Time Frame
Days 0 (baseline) and 14
Title
Change from baseline in weight and waist circumference at Day 14.
Time Frame
Days 0 (baseline) and 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ric M. Procyshyn, Ph.D
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alasdair Barr, Ph.D
Organizational Affiliation
University of British Columbia
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
William Honer, MD
Organizational Affiliation
University of British Columbia
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Randall White, MD
Organizational Affiliation
University of British Columbia
Official's Role
Study Director
Facility Information:
Facility Name
UBC Hospital - Detwiller Pavilion
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2A1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of the Effect of Dosing on Clozapine Levels

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