G6PD Deficiency
Conditions
Keywords
G6PD, Hemolysis, Primaquine, Pharmacokinetics, Malaria
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.
Interventions
DRUGRPQ
The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
DRUGSPQ
The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
DRUGPlacebo
The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
Sponsors
University of Colorado, Denver
University of Mississippi, Oxford
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Methemoglobin concentration in blood from baseline | Days 0, 3, 5 | Change in Methemoglobin concentration in blood from baseline (% hemoglobin) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Primaquine Orthoquinone Plasma concentration, ng/mL | Days 0, 3, 5 | Plasma concentrations of Primaquine Orthoquinone metabolite |
| Change in Hematocrit (%) compared to baseline | Days 0, 3, 5 | Change in Hematocrit (%) compared to baseline |
| Primaquine Plasma Concentration, ng/mL | Days 0, 3, 5 | Plasma concentrations of parent drug |
| 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 |
| Change in Hemoglobin (g/dL) compared to baseline | Days 0, 3, 5 | Change in Hemoglobin (g/dL) compared to baseline |
Countries
United States
Outcome results
None listed