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Recruiting NCT02639702

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

Phase IV Interventional Schizophrenia Schizoaffective Disorder

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Clozapine.
Who it may be relevant to
Registry conditions: Schizophrenia, Schizoaffective Disorder. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Canada
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

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.

Interventions

  • Drug Clozapine
    Switching from twice-daily to once-daily clozapine dosing regimen

Primary outcome measures

  • Brief Psychiatric Rating 18 item Scale (BPRS 18 item scale) [Time frame: 0 and 12 weeks]
Secondary outcome measures (7)
  • Glasgow Antipsychotic Side-effect Scale for Clozapine (GASS-C) [Time frame: 0 and 12 weeks]
  • Brief Evaluation of Psychosis Symptom Domains (BE-PSD) [Time frame: 0 and 12 weeks]
  • Personal and Social Performance scale (PSP) [Time frame: 0 and 12 weeks]
  • Clinical Global Impression - Severity of Illness (CGI-S) [Time frame: 0 and 12 weeks]
  • Brief Neurocognitive Assessment (BNA) [Time frame: 0 and 12 weeks]
  • Subjective Well-being under Neuroleptics scale - Short form (SWNS) [Time frame: 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]

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

Canada · 1 center
  • Centre for Addiction and Mental Health — Toronto

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. PMID 24569099
  • 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. PMID 9555595
  • Agarwal V, Chadda RK. Once daily risperidone in treatment of schizophrenia. Indian J Psychiatry. 2001 Jan;43(1):32-5. PMID 21407835
  • 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. PMID 25649680
  • 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. PMID 12728743
  • 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. PMID 26231009
  • 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. Pharmacop PMID 21969060
  • 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. PMID 27182769

Identifiers

NCT: NCT02639702 · 096/2015

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗