- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02639702
Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia
Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia: A Pilot, Double-Blind, Randomized Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Gary Remington, MD, PhD
- Phone Number: 34750 +1-416-535-8501
- Email: Gary.Remington@camh.ca
Study Contact Backup
- Name: Carol Borlido, BSc
- Phone Number: 34321 416 535-8501
- Email: carol.borlido@camh.ca
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5T 1R8
- Recruiting
- Centre for Addiction and Mental Health
-
Contact:
- Gary Remington, MD, PhD
- Phone Number: 34864 416-535-8501
- Email: Gary.Remington@camh.ca
-
Principal Investigator:
- Gary Remington, MD, PhD
-
Sub-Investigator:
- Hiroyoshi Takeuchi, MD, PhD
-
Sub-Investigator:
- Ofer Agid, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / 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.
|
Switching from twice-daily to once-daily clozapine dosing regimen
Other Names:
|
No Intervention: Maintenance group
Participants will continue to take clozapine twice daily throughout the study period.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brief Psychiatric Rating 18 item Scale (BPRS 18 item scale)
Time Frame: 0 and 12 weeks
|
Change in BPRS total scores from baseline to 12 weeks Total scores range from 18-126, higher scores represent worse clinical outcomes: <31 = Illness not significant >=31 = Mildly ill >41 = Moderately ill >53 = Markedly ill. |
0 and 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Glasgow Antipsychotic Side-effect Scale for Clozapine (GASS-C)
Time Frame: 0 and 12 weeks
|
Detect side effects related to Clozapine from baseline to 12 weeks Higher Scores indicating worse side-effects: 0-16 (absent/mild side-effects) 17-32 (moderate side-effects) 33-48 (severe side-effects) |
0 and 12 weeks
|
Brief Evaluation of Psychosis Symptom Domains (BE-PSD)
Time Frame: 0 and 12 weeks
|
Assess the overall severity of five symptom domains of BE-PSD with a total score in each domain scoring from absent to very severe (i.e.
0-6 with higher scores with worse outcomes)
|
0 and 12 weeks
|
Personal and Social Performance scale (PSP)
Time Frame: 0 and 12 weeks
|
Change in patients social functioning scores from baseline to 12 weeks The PSP is a 100-point single item rating scale from 1-100, subdivided into 10 equal intervals with higher scores indicating better outcomes.
The ratings are based on patient's functioning in four main areas: 1) socially useful activities, 2) personal and social relationships, 3) self-care; and 4) disturbing and aggressive behaviours.
|
0 and 12 weeks
|
Clinical Global Impression - Severity of Illness (CGI-S)
Time Frame: 0 and 12 weeks
|
Assess severity of Illness in Schizophrenia CGI scores from baseline to 12 weeks Scores ranging from normal to the most ill (i.e., scores ranging from 1-7 with higher scores with illness worsening)
|
0 and 12 weeks
|
Brief Neurocognitive Assessment (BNA)
Time Frame: 0 and 12 weeks
|
The BNA is a brief neurocognitive assessment that measures global cognitive impairment in patients with schizophrenia from baseline to 12 weeks.
Negative Z scores (i.e., -0.5 to -2.0 ) indicate mild to severe cognitive impairment.
|
0 and 12 weeks
|
Subjective Well-being under Neuroleptics scale - Short form (SWNS)
Time Frame: 0 and 12 weeks
|
Self report scale to measure well being.
Study assess changes in subjective wellbeing in patients on a neuroleptic from baseline to Week 12. Higher total score indicating better outcomes
|
0 and 12 weeks
|
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
|
Assess changes in level of distress associated with symptoms from no distress to worst distress (i.e., 0-100)
|
0 and 12 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Gary Remington, MD, PhD, Centre for Addiction and Mental Health
Publications and helpful links
General Publications
- Takeuchi H, Fervaha G, Uchida H, Suzuki T, Bies RR, Gronte D, Remington G. Impact of once- versus twice-daily perphenazine dosing on clinical outcomes: an analysis of the CATIE data. J Clin Psychiatry. 2014 May;75(5):506-11. doi: 10.4088/JCP.13m08695.
- Nair NP. Therapeutic equivalence of risperidone given once daily and twice daily in patients with schizophrenia. The Risperidone Study Group. J Clin Psychopharmacol. 1998 Apr;18(2):103-10. doi: 10.1097/00004714-199804000-00002.
- Agarwal V, Chadda RK. Once daily risperidone in treatment of schizophrenia. Indian J Psychiatry. 2001 Jan;43(1):32-5.
- Takeuchi H, Fervaha G, Lee J, Agid O, Remington G. Effectiveness of different dosing regimens of risperidone and olanzapine in schizophrenia. Eur Neuropsychopharmacol. 2015 Mar;25(3):295-302. doi: 10.1016/j.euroneuro.2014.12.008. Epub 2015 Jan 9.
- Chengappa KN, Parepally H, Brar JS, Mullen J, Shilling A, Goldstein JM. A random-assignment, double-blind, clinical trial of once- vs twice-daily administration of quetiapine fumarate in patients with schizophrenia or schizoaffective disorder: a pilot study. Can J Psychiatry. 2003 Apr;48(3):187-94. doi: 10.1177/070674370304800307.
- Sun X, Hamer R, McEvoy J. Asenapine once daily versus twice daily: impact on patient acceptance in a randomized, open-label, 14-day clinical trial. J Clin Psychiatry. 2015 Jul;76(7):992-3. doi: 10.4088/JCP.14l09206. No abstract available.
- Hiemke C, Baumann P, Bergemann N, Conca A, Dietmaier O, Egberts K, Fric M, Gerlach M, Greiner C, Grunder G, Haen E, Havemann-Reinecke U, Jaquenoud Sirot E, Kirchherr H, Laux G, Lutz UC, Messer T, Muller MJ, Pfuhlmann B, Rambeck B, Riederer P, Schoppek B, Stingl J, Uhr M, Ulrich S, Waschgler R, Zernig G. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011. Pharmacopsychiatry. 2011 Sep;44(6):195-235. doi: 10.1055/s-0031-1286287. Epub 2011 Sep 27.
- Takeuchi H, Powell V, Geisler S, DeSanti M, Fervaha G, Agid O, Kane JM, Remington G. Clozapine administration in clinical practice: once-daily versus divided dosing. Acta Psychiatr Scand. 2016 Sep;134(3):234-40. doi: 10.1111/acps.12593. Epub 2016 May 16.
Study record dates
Study Major Dates
Study Start
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Schizophrenia
- Psychotic Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Serotonin Antagonists
- GABA Agents
- GABA Antagonists
- Clozapine
Other Study ID Numbers
- 096/2015
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Schizophrenia
-
Organon and CoCompletedSchizophrenia, Paranoid | Schizophrenia, Disorganized | Schizophrenia, Undifferentiated
-
Organon and CoCompletedSchizophrenia, Paranoid | Schizophrenia, Disorganized | Schizophrenia, Undifferentiated
-
Bradley LegaRecruiting
-
All India Institute of Medical Sciences, BhubaneswarRecruitingTreatment Resistant SchizophreniaIndia
-
King's College LondonSouth London and Maudsley NHS Foundation TrustRecruitingTreatment-resistant Schizophrenia | Healthy Controls | Treatment-responsive SchizophreniaUnited Kingdom
-
University of Sao PauloUnknownRefractory Schizophrenia | Super Refractory SchizophreniaBrazil
-
Rakitzi, StavroulaActive, not recruiting
-
Peking UniversityNot yet recruitingTreatment-resistant Schizophrenia
-
Ohio State UniversityRecruitingTreatment-resistant SchizophreniaUnited States
-
University Hospital, BrestRecruitingSchizophrenia | Schizophrenia Prodromal | Schizophrenia, ChildhoodFrance
Clinical Trials on Clozapine
-
Shanghai Mental Health CenterShanghai Pudong New Area Mental Health Center; The Affiliated Brain Hospital...Completed
-
Shanghai Mental Health CenterUnknown
-
University Hospital, CaenRecruiting
-
Seoul National University Bundang HospitalUnknownSchizophrenia | Schizoaffective DisorderKorea, Republic of
-
Shanghai Mental Health CenterUnknownTreatment-resistant SchizophreniaChina
-
Memorial Hospital of Rhode IslandCompleted
-
Seoul National University HospitalUnknown
-
Saladax Biomedical, Inc.University of Maryland, Baltimore; The Feinstein Institutes for Medical ResearchCompletedPatients Prescribed ClozapineUnited States
-
Manhattan Psychiatric CenterAzur Pharma, IncCompletedSchizophrenia | Schizoaffective DisorderUnited States