Chlorproguanil-Dapsone-Artesunate Versus COARTEM For Uncomplicated Malaria

Malaria, Falciparum Clinical Trial

Official title:

A Multi-centre, Randomised, Double-blind, Double Dummy Study Comparing the Efficacy and Safety of Chlorproguanil-dapsone-artesunate Versus Artemether-lumefantrine in the Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria in Children and Adolescents in Africa.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00344006
• Other study ID #: CDA 714703/005
• Status: Completed
• Phase: Phase 3
• First received: June 22, 2006
• Last updated: December 2, 2016
• Start date: June 2006
• Est. completion date: August 2007

Study information

• Verified date: December 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Nigeria: National Agency for Food and Drug Administration and Control (NAFDAC)Ghana: Food and Drugs Board (FDB)Kenya: Pharmacy and Poisons BoardTazania: Tanzania Food and Drug Authority (TFDA)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1395
• Est. completion date: August 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Months to 14 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

Drug:
• chlorproguanil-dapsone-artesunate

• artemether-lumefantrine

Locations

Country	Name	City	State
Burkina Faso	GSK Investigational Site	Bobo-Dioulasso
Ghana	GSK Investigational Site	Kintampo
Kenya	GSK Investigational Site	Eldoret
Kenya	GSK Investigational Site	Kilifi
Nigeria	GSK Investigational Site	Barkin Ladi
Nigeria	GSK Investigational Site	Calabar
Nigeria	GSK Investigational Site	Enugu
Nigeria	GSK Investigational Site	Ibadan
Tanzania	GSK Investigational Site	Ifakara

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Burkina Faso,  Ghana,  Kenya,  Nigeria,  Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parasitological cure rate, PCR corrected, at day 28 in the PP population The ITT population is a key supportive analysis.
Secondary	Parasitological cure rate, PCR-corrected, at day 14 and 42 ACPR, and ACPR PCR corrected at day 14, 28 and 42 Summary of asexual parasite densities on days 0, 1, 2, 3, 7, 14, 28 and 42 by treatment group.

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