Clinical trial NCT02898779: Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers, Study 1
Official title: Development of Safer Drugs for Malaria in U.S. Troops, Civilian Personnel, and Travelers: Clinical Evaluation of Primaquine Enantiomer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Lead sponsor: University of Mississippi, Oxford
Sponsor class: OTHER
First posted: 2016-09-13
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary outcome: Plasma concentration of parent primaquine and carboyprimaquine following a single dose treatment with primaquine (racemate or enantiomers) not to exceed 45 mg
timeFrame: between 0-24 Hours
Secondary outcomes:
measure: Area Under Curve (AUC) for primaquine up to 24 hours after the primaquine administration
timeFrame: between 0-24 hours
measure: Maximum concentration (Cmax) for primaquine up to 24 hours after the primaquine administration
timeFrame: between 0-24 hours
measure: Area Under Curve (AUC) for carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration
timeFrame: between 0-24 hours
measure: Maximum concentration of carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration
timeFrame: between 0-24 hours
measure: Maximum concentration of selected metabolites primaquine (other than carboxyprimaquine) up to 24 hours after primaquine administration
timeFrame: between 0-24 hours
measure: hemoglobin and methemoglobin levels in the blood after administration of primaquine
timeFrame: 0-72 hours
measure: Genotyping of Cytochrome P-450 (CYP)
timeFrame: day 0
Other outcomes:
Locations:
city: Oxford
country: United States
facility: University of Mississippi
state: Mississippi
Study officials:
affiliation: University of Mississippi Medical Center
name: Babu L Tekwani, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
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