Primaquine Enantiomers in G6PD Deficient Human Volunteers

University of Mississippi, Oxford18 enrolled

Overview

This study is a single center, prospective, cross-over phase 1 trial. Eighteen subjects will be enrolled in the study evaluating the metabolism, pharmacokinetic behavior and tolerability of primaquine enantiomers and placebo over the course of 5 days.

Each subject will receive a 15 mg dose of one enantiomer (SPQ or RPQ or Placebo) daily for up to 5 days, with careful monitoring of hematological parameters before and after each dose. In addition to the general CMP14 safety criteria, any subject who displays a fractional hemoglobin drop of 15% below his/her baseline value, then drug administration will stop (e.g. for baseline Hgb of 14 g/dL, if there is at any point a decrease of 2.1 g/dL). Hematocrit will be similarly monitored, with proportional stop criteria. Elevation in total bilirubin to 2.0 mg/dL or greater will also be used as a stopping criterion. After stopping drug administration (5 days or whenever stop criteria are met), subjects will have a 3-week washout period, and the study repeated with the other enantiomer, and similarly with Placebo.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

G6PD Deficiency

Interventions

RPQDRUG

The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.

SPQDRUG

The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.

PlaceboDRUG

The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * G6PD deficient, otherwise normal healthy adults aged 18 to 65 Exclusion Criteria: * Known history of liver, kidney or hematological disease (other than G6PD deficiency) * Known history of cardiac disease, non-sinus rhythm arrhythmia or QT prolongation * Autoimmune disorders * Report of an active infection * Subject is pregnant or breast-feeding, or is expecting to conceive during the study.

Locations (1)

University of Mississippi

University, Mississippi, United States

Outcomes

Primary Outcomes

Change in Methemoglobin concentration in blood from baseline

Change in Methemoglobin concentration in blood from baseline (% hemoglobin)

Time frame: Days 0, 3, 5

Secondary Outcomes

Primaquine Plasma Concentration, ng/mL

Plasma concentrations of parent drug

Time frame: Days 0, 3, 5

Carboxy-Primaquine Plasma Contration, ng/mL

Plasma concentrations of carboxy-primaquine metabolite

Time frame: Days 0, 3, 5

Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL

Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite

Time frame: Days 0, 3, 5

Primaquine Orthoquinone Plasma concentration, ng/mL

Plasma concentrations of Primaquine Orthoquinone metabolite

Time frame: Days 0, 3, 5

Change in Hematocrit (%) compared to baseline

Time frame: Days 0, 3, 5

Change in Hemoglobin (g/dL) compared to baseline

Time frame: Days 0, 3, 5

Change is AST (U/L) compared to baseline

Change is AST (U/L) compared to baseline; used to monitor liver function

Time frame: Days 0, 3, 5

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.