Pharmacokinetics of Clozapine and Norclozapine and the Effect of Pantoprazole

November 30, 2025 updated by: Orwa Albitar, Universiti Sains Malaysia
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Malaysia
      • Pulau Pinang, Malaysia, 11800
        • Pusat Sejahtera (Kesihatan & Pergigian)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Pregnant or breastfeeding women
  2. Current smokers

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Clozapine
Single dose of 12.5 mg clozapine
Drug: clozapine
Single dose of 12.5 mg clozapine (half 25 mg tablet)
Active Comparator: Clozapine and pantoprazole
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
Single dose of 12.5 mg clozapine (half 25 mg tablet)
Drug: pantoprazole
Five daily doses of pantoprazole tablets 40 mg to be started four days prior to the clozapine administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Plasma Concentration (Cmax)
Time Frame: From pre-dose to 8 hours after a single oral dose of clozapine
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)
Time Frame: From pre-dose to 8 hours after dosing
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf)
Time Frame: From pre-dose to last measurable concentration
Area under the plasma concentration-time curve from time zero extrapolated to infinity
From pre-dose to last measurable concentration
Time to Peak Concentration (Tmax)
Time Frame: From pre-dose to 8 hours after dosing
Time to reach maximum observed plasma concentration of clozapine
From pre-dose to 8 hours after dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universiti Sains Malaysia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 6, 2021

Primary Completion (Actual)

February 28, 2022

Study Completion (Actual)

February 28, 2022

Study Registration Dates

First Submitted

November 19, 2025

First Submitted That Met QC Criteria

November 30, 2025

First Posted (Estimated)

December 4, 2025

Study Record Updates

Last Update Posted (Estimated)

December 4, 2025

Last Update Submitted That Met QC Criteria

November 30, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MY20090488

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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 Healthy Volunteers - Male and Female

Clinical Trials on clozapine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Czech Republic

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe