Genetic Variability in CYP2D6 in U.S Active Duty Population

Phase 1

Completed

• Conditions: Pharmacologic Action
• Interventions: Drug: Primaquine

• Registration Number: NCT02960568
• Lead Sponsor: Walter Reed Army Institute of Research (WRAIR)

Brief Summary

The investigator proposes to 2D6 (Cytochrome P-450 Isoenzyme 2D6) genotype and phenotype a group of active duty service members and assess the effects on primaquine metabolism.

Detailed Description

The investigator propose to enroll a group of active duty service members in order to determine individuals' 2D6 isoenzyme genotype, an enzyme belonging to the hepatic cytochrome P450 oxidase system. The 2D6 isoenzyme is a key enzyme involved in the metabolism of many drugs including the anti-malarial drug primaquine (PQ). By knowing the genotype, the investigator can then categorize each volunteer by CYP2D6 phenotype i.e., expected impact on drug metabolism. In order to further substantiate the relationship between CYP2D6 activity, inadequate metabolism and subsequent primaquine failure, the investigator proposes to assess the effect of 2D6 genetic polymorphisms on PQ metabolism by measuring the PQ pharmacokinetics (PK) over 24 hours following a single 30 mg oral dose in a subset of these Active Duty subjects.

Study Timeline

• Study Start: 2016-01-08
• Study First Submitted: 2016-11-02
• Study First Submitted QC: 2016-11-08
• Study First Posted: 2016-11-09
• Primary Completion: 2017-07
• Study Completion: 2017-08
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-18
• Last Update Posted: 2021-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Primaquine	Primaquine	Poor and Intermediate Metabolizers will receive 30 mg oral primaquine (PQ) and have peripheral blood draws over a 24-hour period to measure PQ pharmacokinetics

Primary Outcome Measures

Name	Time	Method
Measure concentrations of plasma primaquine and its major metabolites.	24 hours
Description of CYP2D6 alleles in an active duty population	1 hour	Genotyping of CYP2D6 alleles will be analyzed by a multiplexed cytometric bead array assay, Luminex xTAG® CYP2D6 Kit v3 (Austin, TX) which allows for detection of the 16 major alleles of 2D6 in the United States: 1,2,3,4,5,6,7,8,9,10,11,15, 17,29, 35,41. Subjects will then be categorized by CYP2D6 phenotype according to standard definitions of enzyme metabolic activity of specific 2D6 alleles using the published activity score model: AS Model A (1): "poor" (PM), "intermediate" (IM), "extensive" (EM) or "ultra (UM)" enzyme activity compared to the general population. Alleles known to have no activity are scored "0", intermediate activity alleles are scored as 0.5, while alleles with normal activity are scored as 1. Scores of both alleles making up the genotype are then added together to give the AS-Model A score and range from 0 to 2, with 0 indicating little or no CYP2D6 activity and 1 or 2 indicating normal levels of CYP2D6. Data will be descriptively analyzed.
Develop pharmacokinetic curves of primaquine and its major metabolites with determinations of Area under the curve (AUC)	1 month

Trial Locations

Locations (1)

WRAIR; 🇺🇸 Silver Spring, Maryland, United States