Chlorproguanil-Dapsone-Artesunate Versus COARTEM For Uncomplicated Malaria

GlaxoSmithKline (GSK)

Status and phase

Completed

Phase 3

Conditions

Malaria, Falciparum

Treatments

Drug: chlorproguanil-dapsone-artesunate

Drug: artemether-lumefantrine

Study type

Interventional

Funder types

Industry

Identifiers

NCT00344006

CDA 714703/005

Details and patient eligibility

About

Chlorproguanil-dapsone has been approved for the treatment of uncomplicated Plasmodium falciparum malaria in a number of countries across sub-Sahara Africa, and by the UK's Medicines and Healthcare products Regulatory Agency.

CDA is a combination of chlorproguanil, dapsone and artesunate, being developed in a public-private partnership with the Medicines for Malaria Venture (MMV), World Health Organisation (WHO-TDR) and academic partners from the London School of Hygiene and Tropical Medicine, University of Liverpool and the Liverpool School of Tropical Medicine as a treatment for acute uncomplicated P. falciparum malaria.

The combination of chlorproguanil-dapsone-artesunate (CDA) is being developed to supersede chlorproguanil-dapsone for the same indication, but the addition of an artemisinin derivative, artesunate, should provide additional population benefits over chlorproguanil-dapsone alone. The artemisinins have been demonstrated to rapidly reduce parasite load and have activity against the sexual stages of the P.falciparum lifecycle. The addition of a second agent to the chlorproguanil-dapsone combination should also protect against the selection of resistant strains of P.falciparum.

Artemether-lumefantrine is the only available fixed-dose Artemisinin-based Combination Therapy actually available and is considered as the gold standard for the treatment of P. falciparum malaria. This study will therefore aim to demonstrate the non-inferiority of the combination of CDA to artemether-lumefantrine in terms of efficacy at 28-days. The key secondary objectives will compare the Parasite Clearance Times (PCT) and the Fever Clearance Times (FCT) between CDA and artemether-lumefantrine.

Enrollment

1,395 patients

Sex

All

Ages

12 months to 14 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Acute, uncomplicated P.falciparum malaria, microscopically confirmed
Temperature at screening of 37.5oC or or more or confirmed history of fever within previous 24 hours
Weigh 7.5kg or over
Screening haemoglobin (Hb) of 7g/dl or over, or haematocrit of 25% or more(If Hb not available at screening)
Willingness to comply with the study visits and procedures, as outlined in the informed consent form
Written or oral witnessed consent has been obtained from parent or guardian
Assent is given by a child aged 12 years or over, in addition to the consent of their parent or guardian

Exclusion criteria

Features of severe/complicated falciparum malaria
Hypersensitivity to active substances (chlorproguanil, dapsone, artesunate, artemether, lumefantrine)
Known allergy to biguanides, sulphones, sulphonamides, artemisinin derived products or aminoalcohol drugs
Known history of G6PD deficiency
Infants with a history of hyperbilirubinaemia during the neonatal period
Use of concomitant medications that may induce haemolysis or haemolytic anaemia from the WHO (World Health Organization) list of essential drugs
Evidence of any concomitant infection at the time of presentation (including P. vivax, P. ovale and P. malariae)
Any other underlying disease that may compromise the diagnosis and the evaluation of the response to the study medication (including clinical symptoms of immunosuppression, tuberculosis, bacterial infection; cardiac or pulmonary disease)
Malnutrition, defined as a child whose weight-for-height is below -3 standard deviations or less than 70% of the median of the NCHS/WHO normalised reference values
Treatment within the past three months with mefloquine or mefloquine-sulphadoxine-pyrimethamine; twenty-eight days with sulphadoxine/pyrimethamine, sulfalene/pyrimethamine, lumefantrine or artemether/lumefantrine, amodiaquine, atovaquone or atovoquone/proguanil, halofantrine; 14-days with chlorproguanil/dapsone, or 7-days with quinine (full course), proguanil, artemisinins, tetracycline doxycycline or clindamycin
Positive sulphadoxine/pyrimethamine urine screen for 'unknown' antimalarial drug use in prior 28-days
Use of an investigational drug within 30 days or 5 half-lives whichever is the longer
Previous participation in this study
Female subjects of child-bearing age, who have had a positive pregnancy test at screening, or do not give their consent to take a pregnancy test
Female subjects who will be breast-feeding an infant for the duration of the study