Phase 2 Efficacy Study of Primaquine and Methylene Blue
- Conditions
- Malaria
- Interventions
- Drug: Sulphadoxine-pyrimethamine
- Registration Number
- NCT02831023
- Lead Sponsor
- University of California, San Francisco
- Brief Summary
The purpose of this study is to determine the most efficacious transmission blocking drug regimen for seasonal malaria chemoprophylaxis in Mali. The primary outcome measure will be the proportion of mosquitoes infected pre and post-treatment, assessed through membrane feeding and measured by oocyst prevalence in mosquitoes dissected on day 7 post feed. Primary endpoint will be a within group comparison between the mean of the pretreatment infectivity (Day 0) and infectivity at 7 days post first dose.
- Detailed Description
Protocol will be shared on request.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 80
- Glucose-6-phosphate dehydrogenase (G6PD) normal defined by CareStart™ G6PD rapid diagnostic test (RDT) or the OSMMR2000 G6PD semi-qualitative test
- Absence of symptomatic falciparum malaria, defined by fever upon enrollment
- Presence of P. falciparum gametocytes on thick blood film at a density >30 gametocytes/µL (i.e. ≥2 gametocytes recorded in the thick film against 500 white blood cells)
- No allergies to study drugs
- No self-reported use of antimalarial drugs over the past 7 days (as reported by the participant)
- Hemoglobin ≥ 10 g/dL
- Individuals weighing <80 kg
- No evidence of severe or chronic disease
- Written, informed consent
- Age < 5 years or > 50 years
- Female gender
- Blood thick film negative for sexual stages of malaria
- Previous reaction to study drugs/known allergy to study drugs
- Signs of severe malaria, including hyperparasitemia, defined as asexual parasitemia > 100,000 parasites / µL)
- Signs of acute or chronic illness, including hepatitis
- Use of other medications (with the exception of paracetamol and/or aspirin)
- Consent not given
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SP-AQ only Sulphadoxine-pyrimethamine Subjects will receive sulphadoxine-pyrimethamine (SP) as single dose and administered in combination with amodiaquine (AQ), which will be given once daily for 3 days. SP-AQ plus PQ Sulphadoxine-pyrimethamine Participants in this arm will receive SP-AQ in combination with a single low dose of primaquine at the World Health Organization (WHO) recommended dose of 0.25 mg/kg. SP-AQ plus PQ 0.25 mg/kg primaquine Participants in this arm will receive SP-AQ in combination with a single low dose of primaquine at the World Health Organization (WHO) recommended dose of 0.25 mg/kg. DP only Dihydroartemisinin-piperaquine Participants in this arm will be treated with dihydroartemisinin-piperaquine (DP), which will be administered once a day for three days. SP-AQ only Amodiaquine Subjects will receive sulphadoxine-pyrimethamine (SP) as single dose and administered in combination with amodiaquine (AQ), which will be given once daily for 3 days. SP-AQ plus PQ Amodiaquine Participants in this arm will receive SP-AQ in combination with a single low dose of primaquine at the World Health Organization (WHO) recommended dose of 0.25 mg/kg. DP plus MB Methylene blue Study participants in this arm will receive DP as described above combined with once-daily methylene blue (MB) for 3 days, at 15 mg/kg/day (45 mg/kg total over 3 days).
- Primary Outcome Measures
Name Time Method Mosquito infectivity assessed through membrane feeding assays 7 day Infectivity will be measured by oocyst prevalence in dissected mosquitoes. Primary endpoint will be a comparison between mean of pretreatment infectivity (day 0) and infectivity at days 2 and 7 post first dose.
- Secondary Outcome Measures
Name Time Method Safety measurements including hemoglobin and signs of hemolysis 42 days The major safety endpoint is hemolysis. For this reason, hemoglobin and methemoglobin values will be measured before treatment, at baseline and on days 1, 2, 3, 7, 14, 28, and 42 post first dose. In addition, clinical review (including additional signs of hemolysis) will be assessed based on active and passive follow-up.
Peak plasma concentration (Cmax) of sulphadoxine-pyrimethamine 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Area under the concentration curve (AUC) of dihydroartemisinin-piperaquine 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Asexual parasite prevalence and density 42 days Asexual parasitemia will be evaluated by blood smear microscopy and confirmed by more sensitive, molecular methods. Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose.
Peak plasma concentration (Cmax) of primaquine 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Peak plasma concentration (Cmax) of methylene blue 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Area under the concentration curve (AUC) of methylene blue 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Elimination half-life (t1/2) of sulphadoxine-pyrimethamine 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Elimination half-life (t1/2) of dihydroartemisinin-piperaquine 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Elimination half life (t1/2) of primaquine 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Elimination half life (t1/2) of methylene blue 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Area under the concentration curve (AUC) of sulphadoxine-pyrimethamine 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Peak plasma concentration (Cmax) of dihydroartemisinin-piperaquine 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Identification of cytochrome P450 (CYP) 2D6 and G6PD polymorphisms 1 hour CYP2D6 and G6PD genotyping will be performed using Thermo Fisher Scientific OpenArray Technology and Copy Number Variation (CNV) assays on the QuantStudio™ 12K Flex Real-Time PCR System.
Gametocyte prevalence, density, and sex ratio measured microscopically and by molecular methods. 42 days Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose.
Area under the concentration curve (AUC) of primaquine. 24 hours Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose.
Trial Locations
- Locations (1)
Malaria Research and Training Centre
🇲🇱Bamako, Mali