Primaquine Enantiomers in G6PD Deficient Human Volunteers
- Conditions
- G6PD Deficiency
- Interventions
- Drug: SPQDrug: PlaceboDrug: RPQ
- Registration Number
- NCT04073953
- Lead Sponsor
- University of Mississippi, Oxford
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
- G6PD deficient, otherwise normal healthy adults aged 18 to 65
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description SPQ (+) enantiomer SPQ 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. Placebo Placebo Cohort 1 will receive placebo capsules every day for 5 days. Cohort 2 will receive placebo capsules every day for five days. RPQ (-) enantiomer RPQ 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.
- Primary Outcome Measures
Name Time Method Change in Methemoglobin concentration in blood from baseline Days 0, 3, 5 Change in Methemoglobin concentration in blood from baseline (% hemoglobin)
- Secondary Outcome Measures
Name Time Method Change in Hematocrit (%) compared to baseline Days 0, 3, 5 Change in Hematocrit (%) compared to baseline
Primaquine Orthoquinone Plasma concentration, ng/mL Days 0, 3, 5 Plasma concentrations of Primaquine Orthoquinone metabolite
Change in Hemoglobin (g/dL) compared to baseline Days 0, 3, 5 Change in Hemoglobin (g/dL) compared to baseline
Primaquine Plasma Concentration, ng/mL Days 0, 3, 5 Plasma concentrations of parent drug
Carboxy-Primaquine Plasma Contration, ng/mL Days 0, 3, 5 Plasma concentrations of carboxy-primaquine metabolite
Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL Days 0, 3, 5 Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite
Change is AST (U/L) compared to baseline Days 0, 3, 5 Change is AST (U/L) compared to baseline; used to monitor liver function
Change in ALT (U/L) compared to baseline Days 0, 3, 5 Change in ALT (U/L) compared to baseline; used to monitor liver function
Change in total Bilirubin (mg/dL) compared to baseline Days 0, 3, 5 Change in total Bilirubin (mg/dL) compared to baseline; used to monitor liver function and red cell integrity
Trial Locations
- Locations (1)
University of Mississippi
🇺🇸University, Mississippi, United States