Title
Primaquine Enantiomers in G6PD Deficient Human Volunteers
Metabolism and Pharmacokinetics of Primaquine Enantiomers in G6PD Deficient Human Volunteers Receiving a Five Day Dose Regimen
Phase
Phase 1Lead Sponsor
University of MississippiStudy Type
InterventionalStatus
Unknown statusIndication/Condition
G6PD DeficiencyStudy Participants
18This 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.
The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
Cohort 1 will receive 15mg of RPQ every day for 5 days. Cohort 2 will receive 22.5 mg of RPQ every day for five days.
Cohort 1 will receive 15mg of SPQ every day for 5 days. Cohort 2 will receive 22.5 mg of SPQ every day for five days.
Cohort 1 will receive placebo capsules every day for 5 days. Cohort 2 will receive placebo capsules every day for five days.
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.
