Pyronaridine Artesunate (3:1) Versus Coartem® in P Falciparum Malaria Patients

This study has been completed.
Sponsor:
Collaborator:
Shin Poong Pharmaceuticals
Information provided by:
Medicines for Malaria Venture
ClinicalTrials.gov Identifier:
NCT00422084
First received: January 12, 2007
Last updated: May 19, 2008
Last verified: May 2008
  Purpose

The purpose of this study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (180:60 mg) with that of Coartem® (artemether lumefantrine) in children and adults with acute uncomplicated P falciparum malaria.


Condition Intervention Phase
Malaria
Drug: Pyronaridine artesunate
Drug: Coartem® (artemether lumefantrine)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Comparative, (Double-Blind, Double-Dummy), Randomised, Multi-Centre, Clinical Study to Assess the Safety and Efficacy of Fixed Dose Formulation of Oral Pyronaridine Artesunate Tablet (180:60 mg) Versus Coartem® (Artemether Lumefantrine) in Children and Adult Patients With Acute Uncomplicated Plasmodium Falciparum Malaria

Resource links provided by NLM:


Further study details as provided by Medicines for Malaria Venture:

Primary Outcome Measures:
  • PCR-corrected adequate clinical and parasitological response (ACPR) rate on Day 28 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Treatment success or failures will be classified according to WHO Guidelines 2005 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Incidence and severity of adverse events and of clinically significant laboratory results, ECG, vital signs or physical examination abnormalities [ Time Frame: Day 28 and Day 42 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of patients with PCR - corrected adequate clinical and parasitological response (ACPR) on Day 14 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
  • Crude ACPR (non-PCR corrected ACPR) on Day 14 and Day 28 [ Time Frame: Day 14 and Day 28 ] [ Designated as safety issue: No ]
  • Parasite Clearance Time [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
  • Fever Clearance Time [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
  • Proportion of patients who have cleared parasites at Day 1, 2 and 3 [ Time Frame: Days 1, 2, 3 ] [ Designated as safety issue: No ]
  • Proportion of patients who have fever cleared at Day 1, 2 and 3 [ Time Frame: Days 1, 2, 3 ] [ Designated as safety issue: No ]

Estimated Enrollment: 1269
Study Start Date: January 2007
Study Completion Date: May 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Pyronaridine artesunate
Drug: Pyronaridine artesunate
once a day for 3 days
Other Name: Pyramax
Active Comparator: 2
Arthemether lumefantrine
Drug: Coartem® (artemether lumefantrine)
twice a day for 3 days
Other Name: Coartem

Detailed Description:

Artemisinin-based combination therapies (ACTs) are considered today by WHO to be the best anti-malarials in terms of efficacy and lower propensity to resistance. Pyronaridine artesunate is a new ACT in development to treat acute uncomplicated malaria. Pyronaridine and artesunate are antimalarial agents with a history of clinical use both separately and in combination with other drugs. Each drug has powerful anti-schizonticidal actions. The aim of a fixed dose combination of pyronaridine and artesunate in the treatment of uncomplicated acute malaria is to provide rapid reduction in parasitemia with a once-daily three-day regimen, thereby improving compliance and reducing the risk of recrudescence through the slower elimination of pyronaridine.

  Eligibility

Ages Eligible for Study:   3 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients between the age 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, in accordance with local practice, 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, lumefantrine or artesunate or other artemisinins.
  • Patients with known disturbances of electrolytes balance, e.g., hypokalaemia or hypomagnesaemia.
  • 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.
  • Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (flecainide, metoprol, imipramine, amitriptyline, clomipramine).
  • Received an investigational drug within the past 4 weeks.
  • Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen. (HBsAg) or Hepatitis C antibody (HCV Ab).
  • Known seropositive HIV antibody.
  • Liver function tests [ASAT/ALAT levels] more than 2.5 times upper limit of normal range.
  • Known significant renal impairment as indicated by serum creatinine of more than 1.4 mg/dL.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00422084

Locations
Congo
Ecole de Santé Publique, Faculté de Médecine, Université de Kinshasa
Kinshasa, DRC, Congo
Gambia
Farafenni Field Station, c/o: MRC Laboratories
Fajara, Gambia
Ghana
Komfo Anoykye Teaching Hospital
Kumasi, Ghana
Indonesia
RSUD TC Hillers
Maumere, Nusa Tenggara Timur, Indonesia, 86113
Jayapura General Hospital (RSUD) DOK II
Jayapura, Papua, Indonesia
Kenya
Siaya District Hospital, Medical Superintendent's office
Siaya Town, Kenya
Mali
Malaria Research and Training Center, Faculté de Médecine, de Pharmacie et d'Ondonto-stomatologie
Bamako, Mali
Mozambique
Instituto Nacional de Saude, Ministero de Saude
Maputo, Mozambique
Philippines
Puerto Princesa General Hospital
Puerto Princesa, Philippines
Senegal
Service de Parasitologie, Faculté de Médecine, Université Cheikh Anta Diop
Dakar, Dakar Fann, Senegal
Sponsors and Collaborators
Medicines for Malaria Venture
Shin Poong Pharmaceuticals
Investigators
Study Director: Claude Oeuvray, PhD Medicines for Malaria Venture
  More Information

Additional Information:
No publications provided by Medicines for Malaria Venture

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Isabelle Borghini Fuhrer, Medicines for Malaria Venture
ClinicalTrials.gov Identifier: NCT00422084     History of Changes
Other Study ID Numbers: SP-C-005-06
Study First Received: January 12, 2007
Last Updated: May 19, 2008
Health Authority: Gambia: MRC Ethics Committee
Senegal: Ministere de la sante
Mali: Ministry of Health
Mozambique: Ministry of Health (MISAU)
Ghana: Ministry of Health
Philippines: Bureau of Food and Drugs
Kenya: Institutional Review Board
Indonesia: Food and Drug Control Agency (BPOM)
République Démocratique du Congo: Ethics Committee Review

Keywords provided by Medicines for Malaria Venture:
Malaria
ACT
P falciparum

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Parasitic Diseases
Protozoan Infections
Artemether
Artemether-lumefantrine combination
Artemisinins
Artesunate
Lumefantrine
Pyronaridine
Amebicides
Anthelmintics
Anti-Infective Agents
Antifungal Agents
Antimalarials
Antiparasitic Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Coccidiostats
Pharmacologic Actions
Schistosomicides
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014