Pharmacokinetics of Clozapine and Norclozapine and the Effect of Pantoprazole

Universiti Sains Malaysia

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers - Male and Female

Treatments: Drug: pantoprazole; Drug: clozapine

Study type: Interventional

Funder types: Other

Identifiers

NCT07262736

MY20090488

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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33 participants in 2 patient groups

Clozapine

Active Comparator group

Description:

Single dose of 12.5 mg clozapine

Treatment:

Drug: clozapine

Clozapine and pantoprazole

Active Comparator group

Description:

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

Treatment:

Drug: clozapine

Drug: pantoprazole