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

• Status: Not yet recruiting
• Trial end date: 2023-01-13
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artesunate-amodiaquine (ASAQ) and artemether-lumefrantrine-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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: London School of Hygiene and Tropical Medicine
• Treatments: Amodiaquine; Amodiaquine, artesunate drug combination; Artemether; Artemether, Lumefantrine Drug Combination; Artesunate; Lumefantrine; Primaquine

Criteria

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