Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia

Sponsor

Centre for Addiction and Mental Health (Other)

Overall Status

Recruiting

CT.gov ID

NCT02639702

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Plasma half-life has routinely been used to establish the dosing schedule of antipsychotics; for example, it is recommended that agents with a short plasma half-life be administered multiple times per day. However, to date, several randomized controlled trials (RCTs) have shown no differences in clinical outcomes between once- and twice-daily dosing of various antipsychotics, suggesting that once-daily dosing of antipsychotics is a viable option regardless of plasma half-life. This would apply to clozapine as well; however, there have been no studies comparing once-daily vs. twice-daily dosing regimens of clozapine in terms of efficacy and tolerability. To address this gap in the literature, the investigators shall conduct a pilot, double-blind, RCT to examine efficacy and tolerability following a switch to once-daily dosing regimen of clozapine in patients with schizophrenia receiving clozapine twice a day.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizoaffective Disorder	Drug: Clozapine	Phase 4

Detailed Description

This issue applies to clozapine as well, in that it has a relatively short plasma half-life of 12-16 hours; of note, the product monographs recommends that clozapine be administered more than once daily if the dose exceeds 200 mg/day in Canada. Despite this, in clinical practice clozapine is frequently administered once daily because of convenience and side effects such as a daytime sedation or somnolence, In support of this, a cross-sectional survey done at the investigators' own centre has revealed that clozapine was prescribed once daily in 75.1% of 676 patients, even though >200 mg/day was administered in 88.6%. However, there have been no studies comparing once-daily vs. twice-daily dosing regimens of clozapine in terms of efficacy and tolerability. To address this gap in the literature, the investigators shall conduct a pilot, double-blind, RCT to examine efficacy and tolerability following a switch to once-daily dosing regimen of clozapine in patients with schizophrenia receiving clozapine twice a day.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia: A Pilot, Double-Blind, Randomized Controlled Trial

Study Start Date :

Aug 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Switch group Participants will receive clozapine once daily at evening or bedtime throughout the study period. If a participant takes ≥200 mg of clozapine at a time other than evening/bedtime, half of this dose will be switched to an evening/bedtime regimen on day 0 (baseline), then another half dose will be switched on day 7 (week 1). Participants will receive placebo in place of the clozapine dose that was switched to evening/bedtime.	Drug: Clozapine Switching from twice-daily to once-daily clozapine dosing regimen Other Names: Clozaril
No Intervention: Maintenance group Participants will continue to take clozapine twice daily throughout the study period.

Arm

Intervention/Treatment

Experimental: Switch group

Participants will receive clozapine once daily at evening or bedtime throughout the study period. If a participant takes ≥200 mg of clozapine at a time other than evening/bedtime, half of this dose will be switched to an evening/bedtime regimen on day 0 (baseline), then another half dose will be switched on day 7 (week 1). Participants will receive placebo in place of the clozapine dose that was switched to evening/bedtime.

Drug: Clozapine

Switching from twice-daily to once-daily clozapine dosing regimen

Other Names:

Clozaril

No Intervention: Maintenance group

Participants will continue to take clozapine twice daily throughout the study period.

Outcome Measures

Primary Outcome Measures

Change in the Brief Psychiatric Rating Scale (BPRS) total scores from baseline to 12 weeks [0 and 12 weeks]

Secondary Outcome Measures

Change in the Glasgow Antipsychotic Side-effect Scale for Clozapine (GASS-C) total scores from baseline to 12 weeks [0 and 12 weeks]
Change in the Brief Evaluation of Psychosis Symptom Domains (BE-PSD) total scores from baseline to 12 weeks [0 and 12 weeks]
Change in the Personal and Social Performance scale (PSP) scores from baseline to 12 weeks [0 and 12 weeks]
Change in the Clinical Global Impression - Severity of Illness (CGI-S) scores from baseline and 12 weeks [0 and 12 weeks]
Change in the Brief Neurocognitive Assessment (BNA) Z scores from baseline to 12 weeks [0 and 12 weeks]
Change in the Subjective Well-being under Neuroleptics scale - Short form (SWNS) total scores from baseline to 12 weeks [0 and 12 weeks]
Change in the Visual Analogue Scale for Distress Associated with Symptoms (VAS-DAS) scores from baseline to 12 weeks [0 and 12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed with schizophrenia or schizoaffective disorder based on DSM-IV criteria
Outpatient status
Ages 18 years or older
Has received clozapine twice a day, one of which is in the evening/bedtime, at the same dose and dosing regimen for at least 3 months
Fluent in English and competent to provide written informed consent