An Open, Randomised, Multi-centre Dose Ranging Phase II Study to Evaluate LAPDAP in Combination With Three Different Doses of Artesunate

GlaxoSmithKline1 site in 1 country120 target enrollmentJune 2003

ConditionsMalaria

DrugsChlorproguanil-dapsone-artesunate (CDA)

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Malaria
Sponsor: GlaxoSmithKline
Enrollment: 120
Locations: 1
Primary Endpoint: Treatment differences between 1,2, or 4mg/kg artesunate with a fixed dose of Chlorproguanil-dapsone (LAPDAP), as measured by determination of PC90 (time to achieve reduction of parasitaemia by 90% of baseline)
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

Drug resistance to a range of antimalarial treatments has become widespread in Africa, South East Asia and South America. Because the rapid spread of drug resistance threatens a public health disaster in these areas of the world and to comply with the WHO-Roll Back Malaria policy of using Artemisinin-based combination therapies (ACT), there is a need to develop new, safe, effective and affordable ACT.

Chlorproguanil-dapsone-artesunate (CDA)is a new ACT that is being developed for the treatment of uncomplicated falciparum malaria in Africa.

Registry

clinicaltrials.gov

Start Date

June 2003

End Date

February 2005

Last Updated

9 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Presentation to a healthcare facility with probable uncomplicated clinical malaria
•Adults aged between 18 and 60 years , or children aged between 12 and 120 months
•Weight between 5 and 85kg
•Pure \[on microscopic grounds\] screening P. falciparum parasitaemia in children from 25,000 to 100,000ul-1, or in adults from 10,000 to 100,000ul-
•\[The parasitaemia range for adults was originally set at 25,000 to 100,000µl-1 and changed to 10,000 to 100,000µl-1 in protocol amendment 3 dated 05 May 2004\]
•Written or oral witnessed consent obtained from subject, parent or guardian
•Compliance with the requirements of the protocol which include a hospital stay of 4 days and 3 nights and regular blood samples by finger-prick (children) or via a cannula (adults)
•A negative pregnancy test for women of child-bearing age on enrolment

Exclusion Criteria

•Features of severe/complicated falciparum malaria
•Known allergy to sulphonamides
•Evidence of any concomitant infection at the time of presentation (including P. ovale and P. malaria)
•Any other underlying disease that would compromise the diagnosis and the evaluation of the response to the study medication (including clinical symptoms of immunosuppression, tuberculosis and bacterial infection)
•Treatment in the 28-days prior to screening with sulfadoxine/pyrimethamine (FANSIDAR, CELOXINE), sulfalene/pyrimethamine (METAKELFIN), mefloquine-sulfadoxinepyrimethamine (FANSIMET), chloroquine\* (NIVAQUINE); treatment in the 21-days prior to screening with mefloquine, or 7-days prior to screening with amodiaquine, halofantrine, quinine (full course), atovaquone - proguanil, artemisinins, co-artemether, tetracycline or clindamycin, or treatment for 5 half-lives prior to screening with drugs that have a potential anti-malarial activity (e.g. co-trimoxazole in the previous 60 hours)
•Use of an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to screening
•Previous participation in this study
•A positive pregnancy test at enrolment, women of child-bearing age who do not take a pregnancy test or female subjects who are breast-feeding an infant for the duration of the study

Outcomes

Primary Outcomes

Treatment differences between 1,2, or 4mg/kg artesunate with a fixed dose of Chlorproguanil-dapsone (LAPDAP), as measured by determination of PC90 (time to achieve reduction of parasitaemia by 90% of baseline)

Secondary Outcomes

The key secondary efficacy endpoint is parasite viability (the proportion of ring-form parasites developing to schizonts) determined from rich adult data and confirmed with more sparse child data