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

NCT00403260 | Completed Phase 3 Results

• 1 other identifier: SP-C-004-06
• Study Type: interventional
• Target: 1,271
• Locations: 7 countries
• Sites: 9

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.

Conditions

Falciparum Malaria

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 28

Secondary Outcomes (7)

• PCR-corrected ACPR on Day 14

  Day 14

• Crude ACPR on Days 14 and 28

  Days 14 and 28

• Parasite Clearance Time

  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

  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

  Days 1, 2 and 3

Study Arms (2)

Pyronaridine - artesunate

EXPERIMENTAL

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

Drug: Pyronaridine - artesunate

Mefloquine plus artesunate

ACTIVE COMPARATOR

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.

Drug: Mefloquine plus artesunate

Interventions

Pyronaridine - artesunate DRUG

once a day for 3 days

Also known as: Pyramax

Pyronaridine - artesunate

Mefloquine plus artesunate DRUG

once a day for 3 days

Mefloquine plus artesunate

Eligibility Criteria

• Age: 3 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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,
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Shin Poong Pharmaceuticals: collaborator

Study Sites (9)

RAOTAP2/Centre Muraz

Bobo-Dioulasso, Houet Province, 01 BP390, Burkina Faso

Location

Pailin Referral Hospital

Pailin, Pailin, Cambodia

Location

Institut Pasteur

Abidjan, Côte d’Ivoire

Location

Wentlock District Hospital

Mangalore, India

Location

Bagamoyo Research and Training Centre of Ifakara Health Institute

Bagamoyo, Tanzania

Location

MaeLamad District Hospital

Mae Ramat, Changwat Tak, Thailand

Location

MaeSod General Hospital

Mae Sot, Changwat Tak, Thailand

Location

NIMPE

Hanoi, Commune Xy, Vietnam

Location

Choray Hospital, Dak O

Ho Chi Minh City, Vietnam

Location

Related Publications (3)

• 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.

  PMID: 22475593 RESULT

• 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.

  PMID: 26666916 DERIVED

• 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.

  PMID: 23433102 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

pyronaridine tetraphosphate, artesunate drug combination; Mefloquine; Artesunate

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Results Point of Contact

• Title: Stephan Duparc, MD
• Organization: Medicines for Malaria Venture

duparcs@mmv.org

+41 22 555 0300

Study Officials

• Isabelle Borghini-Fuhrer, PhD

  Medicines for Malaria Venture

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2006
• First Posted: November 23, 2006
• Study Start: January 1, 2007
• Primary Completion: October 1, 2008
• Study Completion: December 1, 2008
• Last Updated: November 2, 2021
• Results First Posted: September 17, 2021

Record last verified: 2021-10

Locations

CÔ (1); CA (1); TH (2); TA (1); VN (2); IN (1); BU (1)