Pharmacokinetics of Clozapine and Norclozapine and the Effect of Pantoprazole

NCT07262736 | Completed Phase 1

• 1 other identifier: MY20090488
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Clozapine is an effective treatment for patients with schizophrenia who do not respond to other therapies, but its blood concentration varies widely between individuals due to genetic and physiological differences. Proton pump inhibitors such as pantoprazole are often prescribed in this population to prevent stomach discomfort, yet their impact on clozapine exposure has not been fully characterized. This clinical study will investigate the pharmacokinetics of clozapine and its main metabolite norclozapine, the influence of individual characteristics on drug exposure, and the effect of pantoprazole coadministration. Healthy adult volunteers will participate in a randomized open label cross over design, receiving a single dose of clozapine alone and again after pantoprazole treatment. Outcomes include clozapine and norclozapine plasma concentration time profiles, pharmacokinetic parameters, and safety assessments.

Conditions

Healthy Volunteers - Male and Female

Outcome Measures

Primary Outcomes (2)

• Peak Plasma Concentration (Cmax)

  Maximum plasma concentration of clozapine following a single oral dose

  From pre-dose to 8 hours after a single oral dose of clozapine

• Area Under the Plasma Concentration-Time Curve (AUC)

  AUC of clozapine plasma concentration from time zero to the last measurable concentration following a single oral dose

  From pre-dose to 8 hours after dosing

Secondary Outcomes (2)

• Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf)

  From pre-dose to last measurable concentration

• Time to Peak Concentration (Tmax)

  From pre-dose to 8 hours after dosing

Study Arms (2)

Clozapine

ACTIVE COMPARATOR

Single dose of 12.5 mg clozapine

Drug: clozapine

Clozapine and pantoprazole

ACTIVE COMPARATOR

Single dose of 12.5 mg clozapine after five daily doses of pantoprazole tablets 40 mg to be started four days prior to the clozapine administration

Drug: clozapine; Drug: pantoprazole

Interventions

clozapine DRUG

Single dose of 12.5 mg clozapine (half 25 mg tablet)

Clozapine; Clozapine and pantoprazole

pantoprazole DRUG

Five daily doses of pantoprazole tablets 40 mg to be started four days prior to the clozapine administration

Clozapine and pantoprazole

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult volunteers aged 18 to 50 years
• No history of chronic medical or psychiatric disease, as confirmed by baseline medical evaluation, medical history, and electrocardiogram (ECG)
• No use of any medications for at least two weeks before study initiation

You may not qualify if:

• Pregnant or breastfeeding women
• Current smokers

Sponsors & Collaborators

• Universiti Sains Malaysia: lead

Study Sites (1)

Pusat Sejahtera (Kesihatan & Pergigian)

Pulau Pinang, 11800, Malaysia

Location

Related Publications (2)

• Albitar O, Muda MR, Ghadzi SMS, Noor DAM, Ibrahim B, Teh CH, Akkaif MA, Aziz FA. Pharmacogenetics and pharmacometabolomics predictors of clozapine and norclozapine pharmacokinetic exposure in healthy volunteers. Eur J Clin Pharmacol. 2025 Oct;81(10):1429-1438. doi: 10.1007/s00228-025-03884-w. Epub 2025 Jul 22.

  PMID: 40694104 RESULT

• Albitar O, Harun SN, Sheikh Ghadzi SM. Semi-physiological Pharmacokinetic Model of Clozapine and Norclozapine in Healthy, Non-smoking Volunteers: The Impact of Race and Genetics. CNS Drugs. 2024 Jul;38(7):571-581. doi: 10.1007/s40263-024-01092-1. Epub 2024 Jun 5.

  PMID: 38836990 RESULT

MeSH Terms

Interventions

Clozapine; Pantoprazole

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles; Heterocyclic Compounds, 2-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 4, 2025
• Study Start: February 6, 2021
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: December 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

MY (1)