Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers, Study 1

University of Mississippi, Oxford

Status and phase: Completed; Phase 1

Conditions: Malaria

Treatments: Drug: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT02898779

PQ Study 1

Details and patient eligibility

About

To investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers. The specific aim is the comparative evaluation of the metabolism, pharmacokinetic behavior, and tolerability of the isomers of PQ (RPQ and SPQ and the racemic mixture RSPQ) in normal healthy human volunteers.

Full description

The primary objective of this project is to investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers.

The overall approach is as follows: in 36 healthy volunteers with documented normal G6PD activity, we will administer a single oral dose of RPQ, SPQ, or RSPQ. At various times after dosing, we will draw blood samples, in which we will record the plasma levels of the parent drugs, along with plasma and urinary metabolites. The comparative pharmacokinetics, tolerability and hematological effects of these two enantiomers and the racemate will be assessed.

Enrollment: 36 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults (18-60 years of age)
• Informed consent
• Healthy

Exclusion criteria

• Known history of liver, kidney or hematological disease;
• known history of cardiac disease, arrhythmia, QT prolongation;
• Autoimmune disorder;
• Report of an active infection;
• Evidence of G6PD deficiency

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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36 participants in 2 patient groups

Cohort 1 ( Primaquine Low Dose)

Experimental group

Description:

Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers. Cohort 1 (Low Dose Level)- single dose of 15 mg of S-Primaquine and 15 mg of R-Primaquine compared to 30 mg RS-Primaquine over 24 hours. Participants will cross-over after a one week wash-out period.

Treatment:

Drug: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine

Cohort 2 (Primaquine High Dose)

Experimental group

Description:

Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers. Cohort 2 (High Dose Level)-single dose of 22.5 mg of S-Primaquine and 22.5 mg of R-Primaquine compared to 45 mg RS-Primaquine over 24 hours. Participants will cross-over among the treatment arms following a one week wash-out period between each.

Treatment:

Drug: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine