Pyronaridine Artesunate (3:1) Versus Coartem® in P Falciparum Malaria Patients - Full Text View

Sponsors and Collaborators:	Medicines for Malaria Venture Shin Poong Pharmaceuticals
Information provided by:	Medicines for Malaria Venture
ClinicalTrials.gov Identifier:	NCT00422084

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 III

MedlinePlus related topics: Malaria

Drug Information available for: Artesunate Artemether Benflumetol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
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

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
1: Experimental Pyronaridine artesunate	Drug: Pyronaridine artesunate once a day for 3 days
2: Active Comparator Arthemether lumefantrine	Drug: Coartem® (artemether lumefantrine) twice a day for 3 days

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

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

Locations

Congo, DRC
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, Nusa Tenggara Timur
RSUD TC Hillers
Maumere, Nusa Tenggara Timur, Indonesia, 86113
Indonesia, Papua
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, Dakar Fann
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

Medicines for Malaria Venture This link exits the ClinicalTrials.gov site

Shin Poong Pharmaceuticals This link exits the ClinicalTrials.gov site

Responsible Party:	Medicines for Malaria Venture ( Isabelle Borghini Fuhrer )
Study ID Numbers:	SP-C-005-06
Study First Received:	January 12, 2007
Last Updated:	May 19, 2008
ClinicalTrials.gov Identifier:	NCT00422084
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

Study placed in the following topic categories:

Benflumetol
Artesunate
Artemether-lumefantrine combination
Protozoan Infections
Clotrimazole
Pyronaridine

Miconazole
Tioconazole
Parasitic Diseases
Malaria
Artemether
Malaria, Falciparum

Additional relevant MeSH terms:

Anti-Infective Agents
Antiprotozoal Agents
Coccidiosis
Antiplatyhelmintic Agents
Anthelmintics
Schistosomicides
Pharmacologic Actions

Antimalarials
Antiparasitic Agents
Therapeutic Uses
Antifungal Agents
Amebicides
Coccidiostats

ClinicalTrials.gov processed this record on January 16, 2009