DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? •...
Transcript of DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? •...
DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN DIFFERENT ETHNICITIES
QUIQUE BASSAT CRESIB (Barcelona Centre for International Health Research)
Hospital Clinic/University of Barcelona, Spain
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Some history
• Piperaquine developed in China where in
1978 it replaced chloroquine as 1st line
treatment
• Extensively used in MDA there until
abandoned due to the appearance of
resistance
• DHA is the active metabolite of the more
widely used artesunate and artemether.
Developed also in China
What was known regarding DHA/PQP?
• Efficacy over 28—63 days exceeded 95%
• Tolerability uniformly good
• No serious adverse effects identified
Review of 14 studies on 2,636 patients in Southeast Asia and
Africa, mostly adults
What was then needed?
A GMP product that could be studied under GCP in
the following ethnic groups:
• Children from Africa, the primary target
population
• Adults from South East Asia
African trial: 5 countries
301 patients
278 patients
223 patients
447 patients 304 patients
Art/Lum (6-dose regimen):
Day 1 Day 2 Day 3
0 8 Morning Afternoon Morning Afternoon
A large, open label, randomised clinical trial (~1500 children, < 5 years), to
assess DHA/PQP non-inferiority vs. AL
African Study outline
DOSING FOR A CHILD OF 20 Kg
DHA/PQP (3-dose regimen)
Day 1 Day 2 0 24 hours 48 hours
Clinical trials unit in Manhiça, Mozambique
DHA/PQP
AL
In infants, PCR-corrected cure rates > 90% and similar between groups
DHA/PQP is not inferior to AL
p<0.001
97.5%CI>7.6
p=NS
97.5%CI> -3.0
Per Protocol
DHA/PQP protects against new infections
A large, open label, randomised clinical trial (~1150 patients, including
children), in Laos, Thailand, and India to assess DHA/PQP non-inferiority vs.
AS+MQ
Asian Study outline
DHA+PQP (3-dose regimen)
24 48 0
AS + MQ (3-dose regimen)
0 24 48
DOSING FOR A PATIENT OF 40 Kg
75.5
66.4
98.7 97.0
50
60
70
80
90
100
uncorrected cure rate PCR-corrected cure rate
Per Protocol
p=0.002
CI > 3.1%
AS/MQ DHA/PQP
DHA/PQP is not inferior to AS+MQ
p=NS
CI > -0.4%
DHA/PQP protects against new infections
4ABC Trial: the largest non-sponsored DHA-PQP study
• Multicentre (7 countries)
randomised, open label
• Enrolled over 5000 patients
• ACTs: AL, AS/AQ, CDA and
DHA/PQP
• Children: 6-59 months
• Primary endpoint: d28 PCR
corrected ACPR
• CDA arm stopped earlier; in relation to safety concerns from
other trials but also because of its clear lowest efficacy
• AL, ASAQ and DHA/PQP well tolerated, and with few SAEs
• 13 deaths during the 6 month long follow-up, none related to
treatment
Summary of safety and tolerability
Cure rates D28 (uncorrected) Cure rates D28 (corrected)
DHA/PQP was not inferior to other ACTs
Days from start of treatment
Pro
babili
ty tre
atm
ent fa
ilure
fre
e
ASAQ
DHA-PQP
AL
CD+A
0 7 14 21 28 35 42 49 56 63
0.0
0.2
0.4
0.6
0.8
1.0
Treatment failure until Day 63
Proportion of treatment failure free by day of follow up
(ITT population, pooled data over all sites)
DHA/PQP
DHA/PQP PK profile is similar in different ethnic groups
PQP DHA
Asians vs. Caucasians
Conclusions
DHA/PQP
• Is non-inferior to other ACTs
• Is superior to other ACTs in preventing new infections
• Has repeatedly shown good tolerability and safety as other ACTs
• Has simple dosing enhancing adherence
• Does not need a fat meal to increase bioavailability
Thank you!