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

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ClinicalTrials.gov Identifier: NCT02639702
Recruitment Status : Recruiting
First Posted : December 24, 2015
Last Update Posted : May 10, 2019
Sponsor:
Information provided by (Responsible Party):
Gary Remington, Centre for Addiction and Mental Health

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:

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. To date, however, several randomized controlled trials (RCTs) have shown that once-daily dosing of antipsychotics including perphenazine, risperidone, olanzapine, quetiapine, and asenapine is comparable to twice-daily dosing in terms of efficacy and tolerability, suggesting that once-daily dosing of antipsychotics is a viable option regardless of plasma half-life.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 2016
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Clozapine

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 Name: Clozaril

No Intervention: Maintenance group
Participants will continue to take clozapine twice daily throughout the study period.



Primary Outcome Measures :
  1. Change in the Brief Psychiatric Rating Scale (BPRS) total scores from baseline to 12 weeks [ Time Frame: 0 and 12 weeks ]

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


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Exclusion Criteria:

  • Having significant medical or neurological illnesses
  • Pregnant or lactating

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02639702


Contacts
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Contact: Gary Remington, MD, PhD +1-416-535-8501 ext 34864 Gary.Remington@camh.ca

Locations
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Canada, Ontario
Centre for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M5T 1R8
Contact: Gary Remington, MD, PhD    416-535-8501 ext 34864    Gary.Remington@camh.ca   
Principal Investigator: Gary Remington, MD, PhD         
Sub-Investigator: Hiroyoshi Takeuchi, MD, PhD         
Sub-Investigator: Ofer Agid, MD         
Sponsors and Collaborators
Centre for Addiction and Mental Health
Investigators
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Principal Investigator: Gary Remington, MD, PhD Centre for Addiction and Mental Health
Additional Information:
Publications:

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Responsible Party: Gary Remington, Professor, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT02639702    
Other Study ID Numbers: 096/2015
First Posted: December 24, 2015    Key Record Dates
Last Update Posted: May 10, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Gary Remington, Centre for Addiction and Mental Health:
Clozapine
Dosing
Once daily
Regimen
Schizophrenia
Additional relevant MeSH terms:
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Schizophrenia
Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Clozapine
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
GABA Antagonists
GABA Agents