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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RPQ (-) enantiomer | Experimental | 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 |
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| SPQ (+) enantiomer | Experimental | 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 |
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| Primaquine Phosphate | Active Comparator | 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 |
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| Placebo | Placebo Comparator | Cohort 1 will receive placebo (4A) capsules everyday for seven days Cohort 2 will receive placebo (4A) capsules everyday for seven 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 along with the racemic version. |
|
| 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, 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Primaquine Plasma concentration, ng/mL | Plasma concentrations of parent drug | Days 0, 3, 5, 7 |
| Carboxy- Primaquine Plasma concentration, 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, Phd | 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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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.
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Participants will not be able to know the sequence of the drug adminstration
| SPQ | Drug | The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version. |
|
|
| Primaquine Phosphate | Drug | The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version. |
|
|
| Placebo | Drug | The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version. |
|
| Days 0, 3, 5, 7 |
| Primaquine N-carbamoyl-glucuronide Plasma concentration, ng/mL | Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite | Days 0, 3, 5, 7 |
| Primaquine Orthoquinone Plasma concentration, ng/mL | Plasma concentrations of Primaquine Orthoquinone metabolite | Days 0, 3, 5, 7 |
| Change in Hematocrit (%) Compared to baseline | Change in Hematocrit (%) Compared to baseline | Days 0, 3, 5, 7 |
| Change in Hemoglobin (g/dL) Compared to baseline | Change in Hemoglobin (g/dL) Compared to baseline | Days 0, 3, 5, 7 |
| Change in AST (U/L) Compared to baseline | Change in Aspartate aminotransferase (U/L) Compared to baseline; used to monitor liver function | Days 0, 3, 5, 7 |
| Change in ALT (U/L) Compared to baseline | Change in Alanine aminotransferase (U/L) Compared to baseline; used to monitor liver function | Days 0, 3, 5, 7 |
| 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, 7 |
| ID | Term |
|---|---|
| D008288 | Malaria |
| D005955 | Glucosephosphate Dehydrogenase Deficiency |
| D006461 | Hemolysis |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| 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 |
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| ID | Term |
|---|---|
| D011319 | Primaquine |
| ID | Term |
|---|---|
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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