Malaria, Glucose 6 Phosphate Dehydrogenase Deficiency
Conditions
Keywords
Hemolysis, Primaquine, Pharmacokinetics
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.
Interventions
DRUGRPQ
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
DRUGSPQ
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
DRUGPlacebo
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
Sponsors
University of Mississippi, Oxford
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Masking description
Participants will not be able to know the sequence of the drug adminstration
Intervention model description
This study is a single center, prospective, cross-over phase 1 trial. Thirty-six participants will be enrolled into a two Cohort pharmacokinetic study evaluating the metabolism, pharmacokinetic behavior and tolerability of two dose levels (low/high) of primaquine enantiomers (and placebo) over the course of 7 days. Placebo will be added in order to assess tolerability of enantiomers. Placebo control is needed in non-drug related clinical responses.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Normal, healthy adults aged 18 to 65 years
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Methemoglobin concentration in blood from baseline | Days 0, 3, 5, 7 | Change in Methemoglobin concentration in blood from baseline (% hemoglobin) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Primaquine Orthoquinone Plasma concentration, ng/mL | Days 0, 3, 5, 7 | Plasma concentrations of Primaquine Orthoquinone metabolite |
| 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 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 |
| 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 |
| 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 |
| Change in Hemoglobin (g/dL) Compared to baseline | Days 0, 3, 5, 7 | Change in Hemoglobin (g/dL) Compared to baseline |
Countries
United States
Outcome results
None listed