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

NCT02639702 | Recruiting Phase 4

• 1 other identifier: 096/2015
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Clozapine; Dosing; Once daily; Regimen; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Brief Psychiatric Rating 18 item Scale (BPRS 18 item scale)

  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 Outcomes (7)

• Glasgow Antipsychotic Side-effect Scale for Clozapine (GASS-C)

  0 and 12 weeks

• Brief Evaluation of Psychosis Symptom Domains (BE-PSD)

  0 and 12 weeks

• Personal and Social Performance scale (PSP)

  0 and 12 weeks

• Clinical Global Impression - Severity of Illness (CGI-S)

  0 and 12 weeks

• Brief Neurocognitive Assessment (BNA)

  0 and 12 weeks

Study Arms (2)

Switch group

EXPERIMENTAL

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

Maintenance group

NO INTERVENTION

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

Interventions

Clozapine DRUG

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

Also known as: Clozaril

Switch group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Having significant medical or neurological illnesses
• Pregnant or lactating

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

RECRUITING

Related Publications (8)

• 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 BACKGROUND

• 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 BACKGROUND

• Agarwal V, Chadda RK. Once daily risperidone in treatment of schizophrenia. Indian J Psychiatry. 2001 Jan;43(1):32-5.

  PMID: 21407835 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 21969060 BACKGROUND

• 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 BACKGROUND

Related Links

• The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Clozapine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Gary Remington, MD, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gary Remington, MD, PhD

CONTACT

+1-416-535-8501; Gary.Remington@camh.ca

Carol Borlido, BSc

CONTACT

416 535-8501; carol.borlido@camh.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 18, 2015
• First Posted: December 24, 2015
• Study Start: August 1, 2016
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 7, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)