Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen
- Conditions
- MalariaGlucose 6 Phosphate Dehydrogenase Deficiency
- Interventions
- Registration Number
- NCT03934450
- Lead Sponsor
- University of Mississippi, Oxford
- Brief Summary
To investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers, receiving study drug over the course of 7 days.
- 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. Based on the results of this study, if one enantiomer seems to show a better safety profile (in terms of hematological effects), an analogous study will be carried out in G6PD deficient individuals (under a separate protocol). The studies are primarily aimed at understanding the tolerability and safety of the enantiomers in G6PD deficiency. If one shows a better safety profile, ultimately the evaluation of its efficacy will be required.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
- Normal, healthy adults aged 18 to 65 years
- Known history of liver, kidney or hematological disease
- Known history of cardiac disease, Non Sinus Rhythm arrhythmia or QT prolongation
- Autoimmune disorders
- Report of an active infection
- Evidence of G6PD deficiency
- Participant 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 Primaquine Phosphate Primaquine Phosphate Cohort 1 will receive 30 mg of RSPQ (1A) every day for 7 days Cohort 2 will receive 45 mg of RSPQ (1A) every day for 7 days Placebo Placebo Cohort 1 will receive placebo (4A) capsules everyday for seven days Cohort 2 will receive placebo (4A) capsules everyday for seven days RPQ (-) enantiomer RPQ Cohort 1 will receive 15 mg of RPQ (3A) every day for 7 days Cohort 2 will receive 22.5 mg of RPQ (3A) every day for 7 days SPQ (+) enantiomer SPQ Cohort 1 will receive 15 mg of SPQ (2A) every day for 7 days Cohort 2 will receive 22.5 mg of SPQ (2A) every day for 7 days
- Primary Outcome Measures
Name Time Method Change in Methemoglobin concentration in blood from baseline Days 0, 3, 5, 7 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, 7 Change in Hematocrit (%) Compared to baseline
Primaquine Plasma concentration, ng/mL Days 0, 3, 5, 7 Plasma concentrations of parent drug
Change in Hemoglobin (g/dL) Compared to baseline Days 0, 3, 5, 7 Change in Hemoglobin (g/dL) Compared to baseline
Change in AST (U/L) Compared to baseline Days 0, 3, 5, 7 Change in Aspartate aminotransferase (U/L) Compared to baseline; used to monitor liver function
Carboxy- Primaquine Plasma concentration, ng/mL Days 0, 3, 5, 7 Plasma concentrations of carboxy-primaquine metabolite
Primaquine N-carbamoyl-glucuronide Plasma concentration, ng/mL Days 0, 3, 5, 7 Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite
Change in Total Bilirubin (mg/dL) Compared to baseline Days 0, 3, 5, 7 Change in Total Bilirubin (mg/dL) Compared to baseline; used to monitor liver function and red cell integrity
Primaquine Orthoquinone Plasma concentration, ng/mL Days 0, 3, 5, 7 Plasma concentrations of Primaquine Orthoquinone metabolite
Change in ALT (U/L) Compared to baseline Days 0, 3, 5, 7 Change in Alanine aminotransferase (U/L) Compared to baseline; used to monitor liver function
Trial Locations
- Locations (1)
University of Mississippi
🇺🇸University, Mississippi, United States