Gametocytocidal and Transmission-blocking Efficacy of ASAQ and ALAQ With or Without PQ in Mali

London School of Hygiene and Tropical Medicine100 enrolled

Overview

The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine-amodiaquine (ALAQ) with and without a single dose of 0.25mg/kg primaquine (PQ). Outcome measures will include infectivity to mosquitoes at 2, 7 and 14 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density and the frequency of adverse events.

Full protocol available on request

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

100

Conditions

Malaria,Falciparum

Interventions

Artesunate-amodiaquine combinationDRUG

Tablets containing 50mg/135 mg or 100mg/270 mg of artesunate/amodiaquine will be administered according to weight as per manufacturer guidelines

Primaquine PhosphateDRUG

The single dose of 0.25mg/kg PQ will be administered in an aqueous solution, according to a standard operating procedure (SOP) provided by the manufacturer.

Artemether-lumefantrineDRUG

Tablets containing 20 mg artemether and 120 mg lumefantrine will be administered according to weight as per manufacturer guidelines

Eligibility

Sex: ALLMin age: 10 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 10 years and ≤ 50 years * Absence of symptomatic falciparum malaria, defined by fever on enrolment * Presence of P. falciparum gametocytes on thick blood film at a density \>16 gametocytes/µL (i.e. ≥ gametocytes recorded in the thick film against 500 white blood cells) * Absence of other non-P. falciparum species on blood film * Haemoglobin ≥ 10 g/dL * Individuals weighing \< = 80 kg * No evidence of acute severe or chronic disease * Written, informed consent Exclusion Criteria: * Women who are pregnant or lactating (tested at baseline). Urine and/or serum pregnancy testing (β-hCG) will be used. * Detection of a non-P. falciparum species by microscopy * Previous reaction to study drugs / known allergy to study drugs, such as sudden high fevers, shaking or severe sore throat or ulcers in the mouth during treatment with Amodiaquine * Current eye disease with retinal damage * Signs of severe malaria, including hyperparasitaemia (defined as asexual parasitaemia \> 100,000 parasites / µL) * Signs of acute or chronic illness, including hepatitis * The use of other medication (except for paracetamol and/or aspirin), including antacids, other medicines used to treat malaria, abnormal heart rhythm, depression or mental illness or HIV/AIDS, and medicines that have antibiotic/antifungal properties * Use of antimalarial drugs over the past 7 days (as reported by the participant) * Clinically significant illness (intercurrent illness e.g., pneumonia, pre-existing condition e.g., renal disease or HIV/AIDS, malignancy or conditions that may affect absorption of study medication e.g., severe diarrhoea or any signs of malnutrition as defined clinically) * Signs of hepatic injury (such as nausea and/or abdominal pain associated with jaundice) or known severe liver disease (i.e., decompensated cirrhosis, Child Pugh stage B or C) * Signs, symptoms or known renal impairment * Clinically significant abnormal laboratory values as determined by history, physical examination, or routine blood chemistries and haematology values (laboratory guideline values for exclusion are haemoglobin \< 10 g/dL, platelets \< 50,000/μl, White Blood Cell count (WBC) \< 2000/μl, serum creatinine \>2.0mg/dL, or ALT more than 3 times the upper limit of normal for age. * Blood transfusion in the last 90 days. * Known Electrocardiogram (ECG) corrected QT interval of more than 450 ms * Documented or self-reported history of cardiac conduction problems * Documented or self-reported history of epileptic seizures

Locations (1)

Malaria Research and Training Centre

Bamako, Mali

Outcomes

Primary Outcomes

Change in mosquito infection rate assessed through membrane feeding assays

Within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline (day 0, pre-treatment) to day 2 post treatment in the ASAQ, ASAQ-PQ, AL, ALAQ and ALAQ-PQ arms.

Time frame: 2 days (days 0 and 2): 3 day span

Secondary Outcomes

Change in mosquito infection rate assessed through membrane feeding assays (all timepoints)

Within person percent change (presented as percent reduction) in mosquito infection rate from baseline to all feeding time-points, with comparison within and between arms.

Time frame: 6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span

Mosquito infection rate assessed through membrane feeding assays

Mosquito infection rate at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.

Time frame: 6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span

Human infectivity to locally reared mosquitoes assessed through membrane feeding assays

Infectivity to mosquitoes at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.

Time frame: 6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span

Mosquito infection density assessed through membrane feeding assays

Oocyst intensity (in all/all infected mosquitoes) at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms.

Time frame: 6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span

Gametocyte infectivity

Data from ClinicalTrials.gov

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