Call for letters of interest - CDA in Phase III studies
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Dear All,
There is a call put out by WHO/TDR for letters of interest for
phase III studies on Chlorproguanil-dapsone-artesunate (CDA).
The link to the website is:
http://www.who.int/tdr/grants/grants/animalarial_e.htm
Please accept my apology if it has been posted here already.
Best Regards,
Frank Baiden
Navrongo
mailto:fbaiden@hotmail.com
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Call for letters of interest: Chlorproguanil-dapsone-artesunate
(CDA) in two safety and efficacy Phase III studies
The UNICEF/UNDP/World Bank/WHO Special Programme for Research
and Training in Tropical Diseases (TDR), the Medicines for Ma-
laria Venture (MMV) and GlaxoSmithKline (GSK) invite letters of
interests to participate in two safety and efficacy Phase III
studies of chlorproguanil-dapsone-artesunate (CDA) in the treat-
ment of uncomplicated P. falciparum malaria in Africa. One study
will compare CDA to chlorproguanil/dapsone (LapdapTM; study 1),
the other will compare CDA to artemether/lumefantrine (study 2).
These studies will be used to support the regulatory submissions
of CDA by GSK.
The target start date for both studies is the beginning of the
3rd Quarter 2005, with recruitment phase of 6 to 12 months.
Background
The antifolate antimalarial chlorproguanil/dapsone, is indicated
for the treatment of adults and children over 5 kg in weight
with acute, uncomplicated P. falciparum malaria, including those
strains resistant to other antimalarial drugs, especially
chloroquine and sulfadoxine-pyrimethamine.
Artesunate, and other artemisinins, are currently being used in
combination with other anti-malarials as Artemisinin-based Com-
bination Therapy, as recommended by the WHO-Roll Back Malaria
Partnership. Artesunate, the most widely used member of the ar-
temisinin class, is orally active and has been shown to be ef-
fective in multidrug resistant P.falciparum malaria when given
orally or intravenously for 5-7 days.
CDA is a combination of chlorproguanil/dapsone and artesunate.
It is considered to be an appropriate combination because resis-
tance to chlorproguanil/dapsone is not currently an issue in Af-
rica and because the relatively short half-lives (t1/2) of both
chlorproguanil and dapsone make for a suitable kinetic match
with artesunate. The purpose of the combination of chlorprogua-
nil/dapsone and artesunate is to increase the overall efficacy
and increase parasite kill rate, reducing the chance that any
parasite escapes treatment. The short half-lives of the three
component drugs should also reduce the selective pressure for
resistance.
CDA dosing will be as a single dose daily for three days. Dosing
will be on a mg/kg basis, with target doses of 2 mg/kg for
chlorproguanil, 2.5 mg/kg for dapsone and either 2 mg/kg or 4
mg/kg for artesunate (dose to be determined from an ongoing
Phase II study). CDA tablets will be available in two strengths
to facilitate paediatric dosing.
Study 1: CDA compared to chlorproguanil-dapsone
CDA will be compared with chlorproguanil/dapsone in a multi-
centre, double-blind, double-dummy, randomised study.
This study will enrol adults and children > 5 kg in weight (in-
cluding adolescents). Male and female patients will be enrolled.
A total of 970 patients are needed, enrolled across multiple
study sites in sub-Saharan Africa.
CDA dosing will be a single daily dose for three days.
Chlorproguanil/dapsone dosing will be also a single daily dose
for three days
The study will be conducted in patients with uncomplicated P.
falciparum malaria who will be managed as out-patients, but will
be seen daily in order to supervise therapy.
The study objectives are: Efficacy (including adequate clinical
and parasitological response (ACPR) at 14 and 28 days, PCR cor-
rected; parasite reduction at 24 hours; gametocyte carriage)
Safety and tolerability (including haematological assessment in
G6PD deficient and non-deficient subjects; adverse events (AE)
and serious adverse events (SAE) reporting)
Population pharmacokinetics
Study 2: CDA compared to artemether/lumefantrine
CDA will be compared with artemether/lumefantrine in a multi-
centre, double-blind, double-dummy, randomised study.
This study will enrol male and female children from a minimum
weight of 10 kg up to (and including) 14 years of age. The lower
weight limit for this study may be reduced to 5 kg in due
course.
A total of 714 patients are needed, enrolled across multiple
study sites in sub-Saharan Africa.
CDA dosing will be as a single daily dose for three days.
Artemether/lumefantrine dosing will be a 6 dose regimen of arte-
mether/lumefantrine, given twice daily over 3 days.
The study will be conducted in patients with uncomplicated P.
falciparum malaria who will be initially managed in hospital in
order to supervise the twice daily dosing.
The study objectives are:
Efficacy (including ACPR at 14 and 28 days, PCR corrected; fever
clearance time; gametocyte clearance time; parasite clearance
times)
Safety and tolerability (including haematological assessment in
G6PD deficient and non-G6PD deficient subjects; AE and SAE re-
porting)
Population pharmacokinetics
Who should apply?
Letters of intent are sought from African research institutions,
research clinics and health care facilities where malaria pa-
tients are treated, where capacity for follow-up of patients and
laboratory facilities exist.
Selection process
Responses to this call for interest will be reviewed by a panel
of GSK, WHO-TDR and MMV staff to short-list potential sites to
participate. A second round of information will be requested
from short-listed sites specifically related to the study proto-
cols (in this instance, the study protocols will be provided by
the PDT).
How to apply
Letters of intent should be submitted using the following ques-
tionnaire providing all the requested information.
Form in English: Word (44 Kb):
http://www.who.int/tdr/grants/grants/files/antimalarial_e.doc
Adobe PDF: (21 Kb):
http://www.who.int/tdr/grants/grants/files/antimalarial_e.pdf
Form in French: Word (55 Kb):
http://www.who.int/tdr/grants/grants/files/antimalarial_f.doc
Adobe PDF (25 Kb):
http://www.who.int/tdr/grants/grants/files/antimalarial_f.pdf
All applications must be received by no later than Friday 29th
October 2004
Completed questionnaires should be returned to Dr Tom Kanyok at
the address below, marked "CDA studies".
Dr Tom Kanyok
UNICEF/UNDP/World Bank/WHO Special Programme
For Research and Training in Tropical Diseases
World Health Organisation
20 Avenue Appia
CH-1211 Geneva 27
Switzerland (Suisse)
http://www.who.int/tdr/topmenu/staff/kanyok.htm