Malaria, FalciparumPhase 3NCT00371735
Chlorproguanil-Dapsone-Artesunate (CDA) Versus Chlorproguanil-Dapsone (LAPDAP) For Uncomplicated Malaria
A Phase 3 study testing chlorproguanil-dapsone-artesunate and chlorproguanil-dapsone in people with Malaria, Falciparum, run by GlaxoSmithKline at 7 sites in 4 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 12 months and older
- Conditions the study is for
- Malaria, Falciparum
- What is being tested?
- chlorproguanil-dapsone-artesunate and chlorproguanil-dapsone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 900 participants
- Where
- 7 sitesin 4 countries
- Study dates
- Apr 2006to May 2007
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Nigeria4 sites
GSK Investigational Site
Ile-Ife
GSK Investigational Site
Jos
GSK Investigational Site
Lagos
GSK Investigational Site
Maiduguri
About this study
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.
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.
- Conditions
- Malaria, Falciparum
- Being tested
- chlorproguanil-dapsone-artesunate, chlorproguanil-dapsone
- Keywords
- Malaria CDA LAPDAP Africa
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
chlorproguanil-dapsone-artesunateDrug
chlorproguanil-dapsoneDrug
Also called chlorproguanil-dapsone-artesunate
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: chlorproguanil-dapsone-artesunate; Drug: chlorproguanil-dapsone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (1)
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2006 (estimated)
- Study startApr 2006
- Primary completionMay 2007
- Study completionMay 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malaria, FalciparumStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 900 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00371735
- Sponsor's protocol ID
- CDA 714703/006
- Status last verified
- Dec 2016
- First submitted
- 1 Sep 2006
- Last updated
- 5 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Pamba A, Richardson ND, Carter N, Duparc S, Premji Z, Tiono AB, Luzzatto L. Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone. Blood. 2012 Nov 15;120(20):4123-33. doi: 10.1182/blood-2012-03-416032. Epub 2012 Sep 19.
PubMed 22993389Carter N, Pamba A, Duparc S, Waitumbi JN. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials. Malar J. 2011 Aug 17;10:241. doi: 10.1186/1475-2875-10-241.
PubMed 21849081
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00371735
- Acronym / sponsor ID
- CDA 714703/006
- Conditions
- Malaria, Falciparum
- Keywords
- Malaria CDA LAPDAP Africa
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 900 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Apr 2006
- Primary completion
- May 2007 (actual)
- Study completion
- May 2007 (actual)
- First posted
- 4 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: chlorproguanil-dapsone-artesunate, Drug: chlorproguanil-dapsone |
Who may qualify
- Ages
- 12 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| chlorproguanil-dapsone-artesunate | Drug | Arm 1 |
| chlorproguanil-dapsoneAlso: chlorproguanil-dapsone-artesunate | Drug | Arm 1 |
Primary outcome
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.
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2016.
- Derived from this study: PubMed 22993389Pamba A, Richardson ND, Carter N, Duparc S, Premji Z, Tiono AB, Luzzatto L. Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone. Blood. 2012 Nov 15;120(20):4123-33. doi: 10.1182/blood-2012-03-416032. Epub 2012 Sep 19.
- Derived from this study: PubMed 21849081Carter N, Pamba A, Duparc S, Waitumbi JN. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials. Malar J. 2011 Aug 17;10:241. doi: 10.1186/1475-2875-10-241.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing chlorproguanil-dapsone-artesunate and chlorproguanil-dapsone in people with Malaria, Falciparum, run by GlaxoSmithKline at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Nigeria, Burkina Faso, Ghana, Mali. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00371735, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2016.