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| Name | Class |
|---|---|
| University of Colorado, Denver | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RPQ (-) enantiomer | Experimental | 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. |
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| SPQ (+) enantiomer | Experimental | 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. |
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| Placebo | Placebo Comparator | Cohort 1 will receive placebo capsules every day for 5 days. Cohort 2 will receive placebo capsules every day for five days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RPQ | Drug | The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Methemoglobin concentration in blood from baseline | Change in Methemoglobin concentration in blood from baseline (% hemoglobin) | Days 0, 3, 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Primaquine Plasma Concentration, ng/mL | Plasma concentrations of parent drug | Days 0, 3, 5 |
| Carboxy-Primaquine Plasma Contration, ng/mL | Plasma concentrations of carboxy-primaquine metabolite |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Larry Walker, Ph.D. | University of Mississippi Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Mississippi | University | Mississippi | 38677 | United States |
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| ID | Term |
|---|---|
| D005955 | Glucosephosphate Dehydrogenase Deficiency |
| D006461 | Hemolysis |
| D008288 | Malaria |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| SPQ | Drug | The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo. |
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| Placebo | Drug | The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo. |
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| Days 0, 3, 5 |
| Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL | Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite | Days 0, 3, 5 |
| Primaquine Orthoquinone Plasma concentration, ng/mL | Plasma concentrations of Primaquine Orthoquinone metabolite | Days 0, 3, 5 |
| Change in Hematocrit (%) compared to baseline | Change in Hematocrit (%) compared to baseline | Days 0, 3, 5 |
| Change in Hemoglobin (g/dL) compared to baseline | Change in Hemoglobin (g/dL) compared to baseline | Days 0, 3, 5 |
| Change is AST (U/L) compared to baseline | Change is AST (U/L) compared to baseline; used to monitor liver function | Days 0, 3, 5 |
| Change in ALT (U/L) compared to baseline | Change in ALT (U/L) compared to baseline; used to monitor liver function | Days 0, 3, 5 |
| Change in total Bilirubin (mg/dL) compared to baseline | Change in total Bilirubin (mg/dL) compared to baseline; used to monitor liver function and red cell integrity | Days 0, 3, 5 |
| D006425 |
| Hemic and Lymphatic Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |