Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics

Schizophrenia Clinical Trial

Official title:

Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics in Schizophrenic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04240496
• Other study ID #: IORG 0009738 N°30
• Status: Completed
• Phase: N/A
• Start date: October 17, 2019
• Est. completion date: December 14, 2019

Study information

• Verified date: January 2020
• Source: University of Monastir
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: December 14, 2019
• Est. primary completion date: December 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Clozapine
• CYP1A2 Polymorphism
• CYP2C19 Polymorphism
• Schizophrenia

Intervention

Other:
• Determination of plasma concentration of clozapine/ Genotyping
Determination of trough plasma concentration of clozapine (C0) Genotyping of CYP1A2 & CYP2C19

Locations

Country	Name	City	State
Tunisia	Faculty of Medecine of Monastir	Monastir

Sponsors (1)

Lead Sponsor	Collaborator
University of Monastir

Country where clinical trial is conducted

Tunisia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	- Technique: PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism)	One and a half months