Phase2a Primaquine Dose Escalation Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of low single-dose primaquine for gametocidal activity against P.falciparum among adult glucose-6-phosphate dehydrogenase (G6PD)-normal malaria patients.

Official Title
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Phase 2a Dose Escalation Study of the Efficacy, Safety, and Pharmacokinetics of Low Dose Primaquine for Gametocytocidal Activity Against P. Falciparum in Sub-Saharan Africa and South East Asia

Conditions
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Malaria

Intervention / Treatment
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* Drug: dihydroartemisinin-piperaquine
* Drug: 0.125 mg/kg Primaquine
* Drug: 0.5 mg/kg Primaquine
* Drug: 0.25 mg/kg Primaquine
* Drug: 0.0625 mg/kg Primaquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Age >= 18 years and < 50 years Malaria blood thick film positive Presence of gametocytes on thick blood film Agrees to admission to study ward for 26 hours post diagnosis and available for follow up visits No allergies to study drugs Hemoglobin >= 8 g/dl No evidence of severe or chronic disease Written, informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: dihydroartemisinin-piperaquine only<br>dihydroartemisinin -piperaquine (DP) only | Drug: dihydroartemisinin-piperaquine<br> <br> |
| Experimental: DP and 0.125 mg/kg primaquine<br>DP and single dose oral 0.125 mg/kg primaquine | Drug: dihydroartemisinin-piperaquine<br> <br> Drug: 0.125 mg/kg Primaquine<br> <br> |
| Experimental: DP and 0.5 mg/kg primaquine<br>DP and single dose oral 0.5 mg/kg primaquine | Drug: dihydroartemisinin-piperaquine<br> <br> Drug: 0.5 mg/kg Primaquine<br> <br> |
| Experimental: DP and 0.25 mg/kg primaquine<br>DP and a single dose oral 0.25 mg/kg primaquine | Drug: dihydroartemisinin-piperaquine<br> <br> Drug: 0.25 mg/kg Primaquine<br> <br> |
| Experimental: DP and 0.0625 mg/kg primaquine<br>DP and a single dose oral 0.0625 mg/kg primaquine | Drug: dihydroartemisinin-piperaquine<br> <br> Drug: 0.0625 mg/kg Primaquine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mosquito infectivity assessed through membrane feeding | Baseline, Days 1, 2, 7 | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gametocyte prevalence and density | Baseline, Hours 2, 6, 12, 24, Days 2, 3, 7, 14, 28 | 28 days | 
| primaquine pharmacokinetics - area under the curve (AUC) of parent drug and metabolite | Hours 1, 2, 3, 4, 6, 8, 12, 24 | 24 hours | 
| asexual parasite prevalence and density | Baseline, Hours 2, 6, 12, 24, Days 2, 3, 7, 14, 28 | 28 days | 
| safety measurements including hemoglobin and signs of hemolysis | Baseline, Days 1, 2, 3, 7, 14, 28 | 28 days |