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Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics

Primary Purpose

CYP1A2 Polymorphism, CYP2C19 Polymorphism, Clozapine

Status
Completed
Phase
Not Applicable
Locations
Tunisia
Study Type
Interventional
Intervention
Determination of plasma concentration of clozapine/ Genotyping
Sponsored by
University of Monastir
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for CYP1A2 Polymorphism

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Faculty of Medecine of Monastir

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Schizophrenic patients

Arm Description

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.

Outcomes

Primary Outcome Measures

Determination of trough plasma concentration of clozapine (C0)
Technique : HPLC/UV (high-performance liquid chromatography associated with a UV detector)

Secondary Outcome Measures

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)

Full Information

First Posted
January 16, 2020
Last Updated
January 21, 2020
Sponsor
University of Monastir
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1. Study Identification

Unique Protocol Identification Number
NCT04240496
Brief Title
Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics
Official Title
Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics in Schizophrenic Patients
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
October 17, 2019 (Actual)
Primary Completion Date
December 14, 2019 (Actual)
Study Completion Date
December 14, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Monastir

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CYP1A2 Polymorphism, CYP2C19 Polymorphism, Clozapine, Schizophrenia

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Schizophrenic patients
Arm Type
Other
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Determination of plasma concentration of clozapine/ Genotyping
Intervention Description
Determination of trough plasma concentration of clozapine (C0) Genotyping of CYP1A2 & CYP2C19
Primary Outcome Measure Information:
Title
Determination of trough plasma concentration of clozapine (C0)
Description
Technique : HPLC/UV (high-performance liquid chromatography associated with a UV detector)
Time Frame
One and a half months
Secondary Outcome Measure Information:
Title
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.
Description
- Technique: PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism)
Time Frame
One and a half months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Faculty of Medecine of Monastir
City
Monastir
ZIP/Postal Code
5000
Country
Tunisia

12. IPD Sharing Statement

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Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics

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