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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00371735
First received: September 1, 2006
Last updated: December 2, 2016
Last verified: December 2016
  Purpose

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.


Condition Intervention Phase
Malaria, Falciparum Drug: chlorproguanil-dapsone-artesunate Drug: chlorproguanil-dapsone Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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:
  • 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.

Enrollment: 900
Study Start Date: April 2006
Study Completion Date: May 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: chlorproguanil-dapsone-artesunate Drug: chlorproguanil-dapsone
Other Name: chlorproguanil-dapsone-artesunate

  Eligibility

Ages Eligible for Study:   12 Months and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00371735

Locations
Burkina Faso
GSK Investigational Site
Ouagadougou, Burkina Faso
Ghana
GSK Investigational Site
Kumasi, Ghana
Mali
GSK Investigational Site
Bamako, Mali
Nigeria
GSK Investigational Site
Ile-Ife, Nigeria
GSK Investigational Site
Jos, Nigeria
GSK Investigational Site
Lagos, Nigeria
GSK Investigational Site
Maiduguri, Nigeria
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: CDA 714703/006
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: CDA 714703/006
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: CDA 714703/006
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: CDA 714703/006
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: CDA 714703/006
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: CDA 714703/006
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: CDA 714703/006
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00371735     History of Changes
Other Study ID Numbers: CDA 714703/006
Study First Received: September 1, 2006
Last Updated: December 2, 2016
Individual Participant Data  
Plan to Share IPD: Yes
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.

Keywords provided by GlaxoSmithKline:
Malaria CDA LAPDAP Africa

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artesunate
Artemisinins
Chlorproguanil
Proguanil
Dapsone
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antimalarials
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Enzyme Inhibitors
Leprostatic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on June 27, 2017