The primary objective of this phase III clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (Pyramax®, PA) with that of the combination of mefloquine plus artesunate (MQ + AS) in children and adults with uncomplicated P falciparum malaria in South East Asia, India and Africa.
This is a multi-centre, comparative, randomised, open-label, parallel-group, non-inferiority study comparing the efficacy and safety of a fixed combination of PA to a loose combination of MQ + AS for patients with acute, symptomatic, uncomplicated P. falciparum malaria. The study population will include 1271 patients, comprising male and female children (≥20 kg body weight) and adults, recruited from study sites in South East Asia, India and Africa. Patients will be randomised in a 2:1 ratio to receive either oral PA (180:60mg tablets) or MQ (250mg tablets) plus AS (100mg tablets) once a day for 3 consecutive days (Days 0, 1, and 2). The study drug will be administered by a Third-Party Investigator unblinded to the study treatment, while the Investigator remains blinded. Patients will be confined to the to the study facility for ≥4 days (Days 0, 1, 2, and 3) and remain near the study site for ≥7 days, or once fever and parasite clearance has been confirmed for ≥24 hours - whichever occurs later. The primary efficacy end point for the study is the proportion of patients with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28. Scheduled follow-up visits will continue until completion of the study at Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event. The primary efficacy end point for the study is the proportion of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28 (defined as the absence of parasitaemia without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure). Scheduled follow-up visits will continue until completion of the study at Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,271
once a day for 3 days
once a day for 3 days
RAOTAP2/Centre Muraz
Bobo-Dioulasso, Houet Province, Burkina Faso
Pailin Referral Hospital
Pailin, Pailin, Cambodia
Institut Pasteur
Abidjan, Côte d’Ivoire
Wentlock District Hospital
Mangalore, India
Percentage of Subjects With PCR-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28
Percentage of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 28, defined as absence of parasitaemia on Day 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure.
Time frame: Day 28
PCR-corrected ACPR on Day 14
Percentage of subjects with PCR-corrected adequate clinical and parasitological response (ACPR) on Day 14, defined as absence of parasitaemia on Day 14 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
Time frame: Day 14
Crude ACPR on Days 14 and 28
Percentage of subjects with adequate clinical and parasitological response (ACPR) on Days 14 and 28, without correction by PCR, defined as absence of parasitaemia on Days 14 and 28 without the subject's meeting any of the criteria of early treatment failure, late clinical failure, or late parasitological failure
Time frame: Days 14 and 28
Parasite Clearance Time
Parasite clearance time was defined as the time from first dosing to time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart.
Time frame: Thick blood films were examined every 8 hours until ≥72 hours or until 2 consecutive negative readings occurred 7 to 25 hours apart, and on Days 3, 7, 14, 21, 28, 35, and 42 (or any other day if the subject returned).
Fever Clearance Time
Fever clearance time was defined as the time from first dosing to first normal reading of temperature (\<37.5°C taken axillary or tympanic; \<38°C taken oral or rectal) for 2 consecutive normal temperature readings taken between 7 and 25 hours apart.
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Bagamoyo Research and Training Centre of Ifakara Health Institute
Bagamoyo, Tanzania
MaeLamad District Hospital
Mae Ramat, Changwat Tak, Thailand
MaeSod General Hospital
Mae Sot, Changwat Tak, Thailand
NIMPE
Hanoi, Commune Xy, Vietnam
Choray Hospital, Dak O
Ho Chi Minh City, Vietnam
Time frame: Every 8 hours over ≥72 hours following first study drug administration or temperature normalisation for ≥2 readings between 7 and 25 hours apart, then at each visit.
Parasite Clearance at Day 1, 2 and 3
Parasite clearance time was defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart.
Time frame: Days 1, 2 and 3
Fever Clearance at Day 1, 2 and 3
Fever clearance time was defined as the time for at least 2 consecutive normal body temperature measurements (\<37.5°C axillary/tympanic or \<38.0°C oral/rectal) to be obtained within an interval of 7 to 25 hours post-dosing.
Time frame: Days 1, 2 and 3
Adverse Events and Clinically Significant Laboratory Results
Cases and severity of adverse events and of clinically significant laboratory results, ECG, vital signs or physical examination abnormalities
Time frame: Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study or resolution of the event, whichever was earlier