Safety and tolerability of ATV-PG and AQ in HV
Research type
Research Study
Full title
A randomized, double-blind, placebo controlled parallel group study in heathy adult subjects to determine the tolerability and safety of atovaquone-proguanil (ATV-PG) co-administered with amodiaquine (AQ)
IRAS ID
260285
Contact name
Ulrike Lorch
Contact email
Sponsor organisation
ICC
Eudract number
2018-004968-60
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 3 months, 3 days
Research summary
We are conducting a trial with the investigational drugs amodiaquine (AQ) and a fixed combination of Atovaquone-Proguanil (ATV-PG), which will be given as Malarone.
WHO recommend, Seasonal Malaria Chemoprevention (SMC) is given to children to prevent malaria, in high risk areas in Africa. Currently, this consists of once daily administration of AQ for 3 consecutive days (plus sulfadoxine-pyrimethamine (SP) once on Day 1), monthly, during the malaria season. Where deployed, SMC prevents three quarters of deaths from malaria.
SPAQ [sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ)] cannot currently be used in some regions of Africa due to drug resistance to SP. MMV (the study Sponsor) are therefore investigating alternative SMC treatments. AQ is a synthetic 4-aminoquinoline that penetrates malaria infected red blood cells (RBCs) and kills the parasite. Malarone is active against the malaria parasite before it enters the RBCs, and once it has entered the RBCs. Malarone interferes with 2 different pathways in the parasite replication. The different mechanisms of action is expected to reduce resistance development.
The efficacy, safety and tolerability of these drugs administered individually, or as parts of other combinations of the two drugs is well established but tolerability when co-administered has not been explored. This study will evaluate whether the tolerability and safety profile of once daily administration of AQ and Malarone for 3 days supports future use in SMC.
52 healthy volunteers, of sub-Saharan African origin, will be randomised into 4 treatment arms, each arm lasting approximately 57 days (20 days for screening, 37 days for dosing and follow up).
Treatment 1: ATV-PG 1000mg-400mg + AQ 600mg.
Treatment 2: ATV-PG 1000mg-400mg + AQ placebo.
Treatment 3: ATV-PG placebo + AQ 600mg.
Treatment 4: ATV-PG placebo + AQ placebo.We will assess safety parameters including physical examination, vital signs, laboratory evaluations, electrocardiograms and monitoring of adverse events.
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
19/SC/0076
Date of REC Opinion
25 Feb 2019
REC opinion
Favourable Opinion