Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics

NCT04240496 | Completed

• 1 other identifier: IORG 0009738 N°30
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CYP1A2 Polymorphism; CYP2C19 Polymorphism; Clozapine; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Determination of trough plasma concentration of clozapine (C0)

  Technique : HPLC/UV (high-performance liquid chromatography associated with a UV detector)

  One and a half months

Secondary Outcomes (1)

• 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.

  One and a half months

Study Arms (1)

Schizophrenic patients

OTHER

* 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

Interventions

Determination of plasma concentration of clozapine/ Genotyping OTHER

Determination of trough plasma concentration of clozapine (C0) Genotyping of CYP1A2 \& CYP2C19

Schizophrenic patients

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Monastir: lead

Study Sites (1)

Faculty of Medecine of Monastir

Monastir, 5000, Tunisia

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Genotype

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Genetic Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident Doctor

Study Record Dates

• First Submitted: January 16, 2020
• First Posted: January 27, 2020
• Study Start: October 17, 2019
• Primary Completion: December 14, 2019
• Study Completion: December 14, 2019
• Last Updated: January 27, 2020

Record last verified: 2020-01

Locations

TU (1)