Pyronaridine - Artesunate (3:1) Versus Mefloquine Plus Artesunate in Plasmodium Falciparum Malaria Patients

NCT ID: NCT00403260

Last Updated: 2021-11-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1271 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2008-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Falciparum Malaria

Keywords

malaria; antimalarial; P falciparum; pyronaridine; artesunate; artemisinin based combination therapy (ACT); pyronaridine artesunate (Pyramax)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pyronaridine - artesunate

Oral pyronaridine artesunate (180:60mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges.

Group Type: EXPERIMENTAL

Pyronaridine - artesunate

Intervention Type: DRUG

once a day for 3 days

Mefloquine plus artesunate

Mefloquine (250mg tablets) plus artesunate (100mg tablets) once a day for 3 consecutive days (Day 0, 1, and 2). Posology based on body weight ranges.

Group Type: ACTIVE_COMPARATOR

Mefloquine plus artesunate

Intervention Type: DRUG

once a day for 3 days

Interventions

Pyronaridine - artesunate

once a day for 3 days

Intervention Type: DRUG

Mefloquine plus artesunate

once a day for 3 days

Intervention Type: DRUG

Other Intervention Names

Pyramax

Eligibility Criteria

Inclusion Criteria

• Male or female patients between the ages of 3 and 60 years, inclusive.
• Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
• Presence of acute uncomplicated P. falciparum mono-infection confirmed by:

1. Fever, as defined by axillary/tympanic temperature ≥37.5°C or oral/rectal temperature ≥38°C, or documented history of fever in the previous 24 hours and,

2. Positive microscopy of P. falciparum with parasite density between 1,000 and 100,000 asexual parasite count/µl of blood

• Written informed consent provided by patient and/or parent/guardian/spouse.
• Ability to swallow oral medication.

Exclusion Criteria

• Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2000.
• Mixed Plasmodium infection.
• Severe vomiting or severe diarrhoea.
• Known history or evidence of clinically significant disorders.
• Presence of significant anaemia, as defined by Hb <8 g/dL.
• Presence of febrile conditions caused by diseases other than malaria.
• Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, mefloquine or artesunate or other artemisinins.
• Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by positive urine test.
• Female patients of child-bearing potential must be neither pregnant (as demonstrated by a negative pregnancy test) nor lactating, and must be willing to take measures to not become pregnant during the study period.
• Presence of significant renal or hepatic impairment.
• Receipt of an investigational drug within the past 4 weeks.
• Known active Hepatitis A IgM, Hepatitis B surface antigen or Hepatitis C antibody.
• Known seropositive HIV antibody.
• Previous participation in any clinical study with PA.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shin Poong Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Medicines for Malaria Venture

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Isabelle Borghini-Fuhrer, PhD

Role: STUDY_DIRECTOR

Medicines for Malaria Venture

Locations

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

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

Countries

Burkina Faso; Cambodia; Côte d’Ivoire; India; Tanzania; Thailand; Vietnam

References

Rueangweerayut R, Phyo AP, Uthaisin C, Poravuth Y, Binh TQ, Tinto H, Penali LK, Valecha N, Tien NT, Abdulla S, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L; Pyronaridine-Artesunate Study Team. Pyronaridine-artesunate versus mefloquine plus artesunate for malaria. N Engl J Med. 2012 Apr 5;366(14):1298-309. doi: 10.1056/NEJMoa1007125.

Reference Type: RESULT

PMID: 22475593 (View on PubMed)

Ayyoub A, Methaneethorn J, Ramharter M, Djimde AA, Tekete M, Duparc S, Borghini-Fuhrer I, Shin JS, Fleckenstein L. Population Pharmacokinetics of Pyronaridine in Pediatric Malaria Patients. Antimicrob Agents Chemother. 2015 Dec 14;60(3):1450-8. doi: 10.1128/AAC.02004-15.

Reference Type: DERIVED

PMID: 26666916 (View on PubMed)

Duparc S, Borghini-Fuhrer I, Craft CJ, Arbe-Barnes S, Miller RM, Shin CS, Fleckenstein L. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malar J. 2013 Feb 21;12:70. doi: 10.1186/1475-2875-12-70.

Reference Type: DERIVED

PMID: 23433102 (View on PubMed)

Other Identifiers

SP-C-004-06

Identifier Type: -

Identifier Source: org_study_id