This study will assess the efficacy of Pyramax administered for three-day, two-day or one day, in clearing a P. falciparum infection in asymptomatic carriers. .
This is a randomized, open-label, three-arm, out-patient study in asymptomatic individuals with P. falciparum monoinfection confirmed at baseline, who are \>5 years of age and \>20kg body weight. A total of 300 participants will be randomised into the study; 100 participants in each of three treatment arms. Patients who fulfil the entry criteria (all inclusion and none of the exclusion criteria) will be recruited and randomized to receive Pyramax orally for three days, two days or one day in a randomization ratio of 1:1:1. All participants will be followed until Day 63 (counted from day 0) and blood samples will be taken on Days 0, 1, 2, 3, 7, 14, 21, 28, 35, 42 and 63 for malaria diagnostics, parasite density and qPCR. In addition, blood samples reverse-transcriptase (RT)-PCR will be taken on Days 0, 1, 2, 3, 7 and 14. Participants will be administered local SOC treatment if they meet any of the protocol-specific criteria of treatment failure: Early treatment failure, Late clinical failure, or Late parasitological failure up to and including Day 63, or if the participant withdraws at any time before Day 63, and is parasite positive.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
300
MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine,
Fajara, City of Banjul, The Gambia
Tropical Diseases Research Centre
Ndola, Zambia
PCR-adjusted APR at Day 28 (based on slide assessment by microscopy)
To assess the efficacy of each dosing regimen PCR-adjusted Adequate parasitological response (APR) at Day 28
Time frame: Day 28
PCR-adjusted APR
To assess the efficacy of each dosing regimen PCR-adjusted APR at Day 63
Time frame: 63 days
PCR-unadjusted APR
To assess the efficacy of each dosing regimen PCR-unadjusted APR at Day 63
Time frame: 63 days
Rate of recurrent infections, recrudescence and new infections
To assess the efficacy of each dosing regimen on rate of recurrent infections, recrudescence and new infections
Time frame: 63 days
Proportion of parasite free participants
Proportion of participants who are parasite free by 4-8 hours, Day 1, Day 2 and Day 3 post first dosing
Time frame: 4 days
Gametocyte incidence
The area under the curve (AUC) up to Day 14 (post first dose) of gametocytes in participants with gametocytes at baseline, and separately in participants without gametocytes at baseline
Time frame: 14 days
Adverse Events
* Number (%) of patients and number of events with: * TEAEs, * serious TEAEs, * study drug related TEAEs, * study drug related serious TEAEs, * malaria-related TEAEs, * malaria-related serious TEAEs * Number (%) of patients with TEAEs and drug-related TEAEs by maximum severity, based on Grade 1 to Grade 5 (CTCAE V4.03) severity grading Adverse events will be coded by MedDRA primary system organ class and preferred term. * Hepatotoxicity related TEAEs o The number and percentage of patients with hepatotoxicity related TEAEs, based on the Standard MedDRA Query (SMQ) narrow search "Drug-related hepatic disorders" will be summarised and clinical biochemistry parameters
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Time frame: 63 days
Clinical laboratory data - Haematology
Haemoglobin, haematocrit, erythrocytes, platelets, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils will be summarised over time, as absolute values and changes from baseline with the number of observations, mean, standard deviation, median, quartiles, minimum and maximum. SI units will be used to summarise the data.
Time frame: 63 days
Clinical laboratory data - Biochemistry
Total and conjugated bilirubin will be summarised over time, as absolute values and changes from baseline with the number of observations, mean, standard deviation, median, quartiles, minimum and maximum. SI units will be used to summarise the data.
Time frame: 63 days
Clinical laboratory data - Liver Enzymes
Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST), Alkaline Phosphatase will be summarised over time, as absolute values and changes from baseline with the number of observations, mean, standard deviation, median, quartiles, minimum and maximum. IU/L units will be used to summarise the data
Time frame: 63 days
Clinical laboratory data - Liver Enzyme Elevations
The number (%) of participants with liver enzyme elevations after first drug administration as defined below will be summarised. * ALT or AST \> 3 x Upper Limit of Normal (ULN) * ALT or AST \> 5 x ULN * ALT or AST \> 8 x ULN * ALT or AST \> 3 x ULN and bilirubin \> 2 x ULN at the same time point (when conjugated bilirubin fraction is missing) * ALT or AST \> 3 x ULN and bilirubin \> 2 x ULN, together with a conjugated bilirubin fraction \>35% (Potential Hy's law cases), at the same time point
Time frame: 63 days
Vital signs - Blood pressure
Supine systolic and diastolic blood pressure (mm Hg) absolute values and changes from baseline will be summarised by time point with the number of observations, mean, standard deviation, median, minimum and maximum, and quartiles
Time frame: 63 days
Vital signs - Pulse rate
Pulse rate (bpm) absolute values and changes from baseline will be summarised by time point with the number of observations, mean, standard deviation, median, minimum and maximum, and quartiles
Time frame: 63 days
Vital signs - Temperature
Temperature (degrees Celsius) absolute values and changes from baseline will be summarised by time point with the number of observations, mean, standard deviation, median, minimum and maximum, and quartiles
Time frame: 63 days