Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics

January 21, 2020 updated by: Dr. Helmi AMMAR, University of Monastir

Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics in Schizophrenic Patients

Clozapine (Clz), an atypical antipsychotic, is the reference medication for patients with treatment-resistant schizophrenia. Due to the high inter-individual variability of its pharmacokinetics and its narrow therapeutic index, a close therapeutic drug monitoring (TDM) of Clz is highly recommended.

Several factors can cause a variation in the pharmacokinetics as age, smoking habits, coffee consumption and drug interaction. Genetic factors related to hepatic expression levels of the cytochrome P450 (CYP), regulate the hepatic clearance of Clz, thereby determine its bioavailability.

The CYP1A2 and CYP2C19 isoenzymes are mainly responsible for the metabolism of several drugs including Clz. It has been demonstrated that there is an interethnic variation in the expression and function of these two isoenzymes. This variation is caused by single nucleotide polymorphisms (SNPs) of genes encoding these proteins.

While the Influence of the different polymorphisms related to CYP1A2 and CYP2C19 have been established especially in Asian and Caucasian populations, no study has examined the impact of these SNPs in the southern Mediterranean populations. Moreover, the impact of these SNPs is very controversial. The present study aims to investigate in Tunisian schizophrenic patients, the influence of genetic (CYP1A2 and CYP2C19 polymorphisms) and non-genetic factors on Clz pharmacokinetics.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Not Applicable

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

  • Tunisia
      • Monastir, Tunisia, 5000
        • Faculty of Medecine of Monastir

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Schizophrenic patients receiving clozapine
  • Good adherence to the treatment (clozapine)

Exclusion Criteria:

  • Patients who were co-prescribed drugs that affected the pharmacokinetics of Clozapine.
  • Patients who presented gastrointestinal disorders disturbing absorption of clozapine.

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: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Schizophrenic patients
  • Determination of trough plasma concentration of clozapine (C0)
  • Genotyping of CYP1A2 & CYP2C19 Drug: Leponex (Clozapine) : was started at a dose of 25 mg/j, the dose was gradually increased and was administered in one, two or three divided doses.
Other: Determination of plasma concentration of clozapine/ Genotyping
Determination of trough plasma concentration of clozapine (C0) Genotyping of CYP1A2 & CYP2C19

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of trough plasma concentration of clozapine (C0)
Time Frame: One and a half months
Technique : HPLC/UV (high-performance liquid chromatography associated with a UV detector)
One and a half months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of the correlation between the presence of CYP1A2*1F (rs762551;-163C> A), CYP1A2*1C (rs2069514;-3860 G> A) and CYP 2C19*2 (rs4244285; 681G>A) and the variability of C0/Daily dose.
Time Frame: One and a half months
- Technique: PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism)
One and a half months

Collaborators and Investigators

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

Sponsor

University of Monastir

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)

October 17, 2019

Primary Completion (Actual)

December 14, 2019

Study Completion (Actual)

December 14, 2019

Study Registration Dates

First Submitted

January 16, 2020

First Submitted That Met QC Criteria

January 21, 2020

First Posted (Actual)

January 27, 2020

Study Record Updates

Last Update Posted (Actual)

January 27, 2020

Last Update Submitted That Met QC Criteria

January 21, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IORG 0009738 N°30

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.

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