Chlorproguanil-Dapsone-Artesunate (CDA) Versus Chlorproguanil-Dapsone (LAPDAP) For Uncomplicated Malaria

December 2, 2016 updated by: GlaxoSmithKline

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

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 HCl (CPG) and dapsone (DDS) as chlorproguanil-dapsone has already been shown to be efficacious against P.falciparum in adults and children in Sub-Sahara Africa. The addition of artesunate to LAPDAP has been demonstrated to increase the parasite kill rate as demonstrated in the phase II study, and reduce the chance of any parasites escaping treatment over the 3-day course. The addition of artesunate is also anticipated to have the population benefit of protection against the development of resistant strains of P.falciparum, although it will not be possible to demonstrate this in a clinical trial. One further population benefit of the artemisinin drugs are their ability to suppress the sexual forms of the parasite (gametocytes), which should reduce infectivity after antimalarial treatment and potentially lower transmission rates with widespread use, including the spread of any parasites resistant to the partner drug.

The aims of this phase III study are to compare the efficacy of a fixed ratio combination tablet of CDA to chlorproguanil-dapsone, and collect supporting safety data. This will be a multi-centre, double-blind, double-dummy, randomised trial, in children, adolescents and adults, with chlorproguanil-dapsone as a comparator.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

900

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Burkina Faso
      • Ouagadougou, Burkina Faso
        • GSK Investigational Site
  • Ghana
      • Kumasi, Ghana
        • GSK Investigational Site
  • Mali
      • Bamako, Mali
        • GSK Investigational Site
  • Nigeria
      • Ile-Ife, Nigeria
        • GSK Investigational Site
      • Jos, Nigeria
        • GSK Investigational Site
      • Lagos, Nigeria
        • GSK Investigational Site
      • Maiduguri, Nigeria
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Acute, uncomplicated P.falciparum malaria, microscopically confirmed infection.
  • Temperature at screening of 37.5oC or over or confirmed history of fever within previous 24-hours.
  • Weight 7.5kg or over , no upper weight limit.
  • Screening haemoglobin (Hb) of 7g/dl, or more or haematocrit of 25% or over(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 obtained from subject, parent or guardian.
  • Assent is given by a child aged 12 to <18years, 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), or excipients of the investigational products.
  • Known allergy to biguanides, sulphones, sulphonamides or artemisinin derived products.
  • Known history of G6PD deficiency.
  • Infants with a history of hyperbilirubinaemia during the neonatal period.
  • Evidence of any concomitant infection at the time of presentation (including P. vivax, P. ovale and P. malariae).
  • Use of concomitant medications that may induce haemolysis or haemolytic anaemia from the WHO (World Health Organization) list of essential drugs.
  • 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 atovaquone/proguanil, halofantrine; 14-days with chlorproguanil/dapsone, or 7-days with quinine (full course), proguanil, artemisinin, 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 potential who have had a positive pregnancy test at enrolment, 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Drug: chlorproguanil-dapsone
Other Names:
  • chlorproguanil-dapsone-artesunate
Drug: chlorproguanil-dapsone-artesunate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Parasitological cure rate, PCR-corrected, at day 28, in the per-protocol population. Parasitological cure rate is defined as the clearance of the initial malaria infection by day 7 and remaining free of this infection to the day of assessment.

Secondary Outcome Measures

Outcome Measure
The proportion of subjects with parasites remaining at 24 hours post-first dose by treatment group. Parasitological cure rate, PCR-corrected, at day 14, by treatment group.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2006

Primary Completion (Actual)

May 1, 2007

Study Completion (Actual)

May 1, 2007

Study Registration Dates

First Submitted

September 1, 2006

First Submitted That Met QC Criteria

September 1, 2006

First Posted (Estimate)

September 4, 2006

Study Record Updates

Last Update Posted (Estimate)

December 5, 2016

Last Update Submitted That Met QC Criteria

December 2, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDA 714703/006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

  1. Annotated Case Report Form
    Information identifier: CDA 714703/006
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Clinical Study Report
    Information identifier: CDA 714703/006
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Individual Participant Data Set
    Information identifier: CDA 714703/006
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Informed Consent Form
    Information identifier: CDA 714703/006
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Study Protocol
    Information identifier: CDA 714703/006
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Dataset Specification
    Information identifier: CDA 714703/006
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  7. Statistical Analysis Plan
    Information identifier: CDA 714703/006
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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