dihydroartemisinin/ piperaquine efficacy and safety in ... · what was known regarding dha/pqp? •...
TRANSCRIPT
![Page 1: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/1.jpg)
DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN DIFFERENT ETHNICITIES
QUIQUE BASSAT CRESIB (Barcelona Centre for International Health Research)
Hospital Clinic/University of Barcelona, Spain
![Page 2: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/2.jpg)
O
OH
O
O
H
H
OR
N
N
N Cl
N
N
N
Cl
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
![Page 3: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/3.jpg)
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
![Page 4: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/4.jpg)
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
![Page 5: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/5.jpg)
African trial: 5 countries
301 patients
278 patients
223 patients
447 patients 304 patients
![Page 6: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/6.jpg)
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
![Page 7: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/7.jpg)
Clinical trials unit in Manhiça, Mozambique
![Page 8: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/8.jpg)
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
![Page 9: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/9.jpg)
DHA/PQP protects against new infections
![Page 10: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/10.jpg)
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
![Page 11: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/11.jpg)
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%
![Page 12: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/12.jpg)
DHA/PQP protects against new infections
![Page 13: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/13.jpg)
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
![Page 14: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/14.jpg)
• 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
![Page 15: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/15.jpg)
Cure rates D28 (uncorrected) Cure rates D28 (corrected)
DHA/PQP was not inferior to other ACTs
![Page 16: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/16.jpg)
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
![Page 17: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/17.jpg)
DHA/PQP PK profile is similar in different ethnic groups
PQP DHA
Asians vs. Caucasians
![Page 18: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/18.jpg)
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
![Page 19: DIHYDROARTEMISININ/ PIPERAQUINE EFFICACY AND SAFETY IN ... · What was known regarding DHA/PQP? • Efficacy over 28—63 days exceeded 95% • Tolerability uniformly good • No](https://reader033.vdocument.in/reader033/viewer/2022050610/5fb177638af99a5ec7476e6d/html5/thumbnails/19.jpg)
Thank you!