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| Name | Class |
|---|---|
| Walter and Eliza Hall Institute of Medical Research | OTHER |
| The University of Western Australia | OTHER |
| University of Oxford | OTHER |
| Curtin University |
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This study specifically seeks to provide data on the safety, tolerability and pilot efficacy of short course, high dose primaquine treatment in Papua New Guinean children aged 5-10 years, in a cross-sectional study design. Community screened asymptomatic cases and/or cases of clinically diagnosed malaria admitted to the out-patient units of the health center, will be screened for Glucose-6-phosphate dehydrogenase deficiency (G6PD) and malaria illness by rapid diagnostic test and P. vivax infection confirmed by light microscopy. Following treatment with artemether-lumefantrine (Coartem), G6PD normal children will be enrolled into the study and followed for 2 months. Primaquine treatment will be allocated to study participants in a step-wise design; firstly receiving the current 14 day treatment regimen of 0.5 mg/kg total dose (n=40); secondly, a 7 day treatment regimen receiving a total dose of 1.0 mg/kg/day; then thirdly, receive 1.0 mg/kg twice daily dose (bd) for a total of 3.5 days, should the 7 day treatment prove to be safe and well tolerated. In addition to this dose-escalation study, the pharmacokinetic profiles of single doses of 0.5 mg/kg and 1.0 mg/kg will be determined using an intensive sampling protocol, in children aged 5-10 years. The pharmacokinetic profiles obtained by this sub-study will be essential for modeling the population pharmacokinetic data obtained from the dose-escalation study. As there is currently no data on the safety, tolerability and efficacy of primaquine in children, the present study will validate previous observation and contribute to the knowledge of primaquine as a treatment for liver stages of Plasmodium vivax infection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 14 day dose regimen | Active Comparator | 0.5 mg/kg oral Primaquine administered daily for 14 days |
|
| 7 day dose regimen | Active Comparator | 1.0 mg/kg oral Primaquine administered daily for 7 days |
|
| 3.5 day dose regimen | Active Comparator | 1.0 mg/kg oral Primaquine administered twice daily (bd) for 3.5 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Primaquine | Drug | Primaquine treatment given in a step-wise manner; (a) 0.5 mg/kg total dose daily for 14 days (n=40), (b) 1.0 mg/kg total dose daily for 7 days (n=40), (c) 1.0 mg/kg twice daily for 3.5 days (n=40) |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability as measured by hemoglobin | 2 months post baseline | |
| Safety and tolerability as measured by methemoglobin | 2 months post baseline | |
| Safety and tolerability as measured by liver biochemistry | 2 months post baseline | |
| Safety and tolerability as measured by symptom questionnaire | 2 months post baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Time to first or only Plasmodium vivax infection by light microscopy and polymerase chain reaction (PCR) | Thick and thin blood films, along with PCR samples, will be collected at time of recruitment and then at any time the participant develops fever within the study period. | 2 months from baseline |
| Time to first or only clinical Plasmodium vivax episode |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Inoni Betuela, MD PhD | Contact | inoni.betuela@pngimr.org.pg | ||
| Ivo Mueller, PhD | Contact | +61393452555 | ivomueller@fastmail.fm |
| Name | Affiliation | Role |
|---|---|---|
| Inoni Betuela, MD, PhD | PNG Institute of Medical Research | Principal Investigator |
| Ivo Mueller, PhD | Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB) |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PNG Institute of Medical Research | Recruiting | Madang | Madang Province | Papua New Guinea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37269941 | Derived | Moore BR, Salman S, Tobe R, Benjamin J, Yadi G, Kasian B, Laman M, Robinson LJ, Page-Sharp M, Betuela I, Batty KT, Manning L, Mueller I, Davis TME. Short-course, high-dose primaquine regimens for the treatment of liver-stage vivax malaria in children. Int J Infect Dis. 2023 Sep;134:114-122. doi: 10.1016/j.ijid.2023.05.063. Epub 2023 Jun 1. |
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| ID | Term |
|---|---|
| D016780 | Malaria, Vivax |
| ID | Term |
|---|---|
| D008288 | Malaria |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D011319 | Primaquine |
| ID | Term |
|---|---|
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| OTHER |
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|
| 2 months from baseline |
| Comparison of the rate of incidence of P. vivax relapses in 3.5 or 7 day treatment arm compared to standard 14 day regimen | 2 months from baseline |
| Pharmacokinetics - elimination half-life (t1/2) | 42 days |
| Pharmacokinetics - clearance (CL) | 42 days |
| Pharmacokinetics - volume of distribution (Vd) | 42 days |
| Pharmacokinetics - maximal concentration (Cmax) | 42 days |
| Pharmacokinetics - area under the curve (AUC) | 42 days |
| J Kevin Baird, PhD | Eijkman-Oxford Clinical Research Unit, Oxford University | Principal Investigator |
| Timothy ME Davis, FRAC, PhD | The University of Western Australia | Principal Investigator |
| D000096724 |
| Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| D006571 | Heterocyclic Compounds |