 | Fiona Macintyre, Yeka Adoke, Alfred B Tiono, Tran Thanh Duong, Ghyslain Mombo-Ngoma, Marielle Bouyou-Akotet, Halidou Tinto, Quique Bassat, Saadou Issifou, Marc Adamy, Helen Demarest, Stephan Duparc, Didier Leroy, Bart E Laurijssens, Sophie Biguenet, Afizi Kibuuka, Antoinette Kitoto Tshefu, Melnick Smith, Chanelle Foster, Illse Leipoldt, Peter G Kremsner, Bui Quang Phuc, Alphonse Ouedraogo, Michael Ramharter, OZ-Piperaquine Study Group A randomised, double-blind clinical phase II trial of the efficacy, safety, tolerability and pharmacokinetics of a single dose combination treatment with artefenomel and piperaquine in adults and children with uncomplicated Plasmodium falciparum malaria (Journal Article) In: BMC Med., vol. 15, no. 1, pp. 181, 2017, ISSN: 1741-7015. @article{Macintyre2017-tq,
title = {A randomised, double-blind clinical phase II trial of the efficacy, safety, tolerability and pharmacokinetics of a single dose combination treatment with artefenomel and piperaquine in adults and children with uncomplicated Plasmodium falciparum malaria},
author = {Fiona Macintyre and Yeka Adoke and Alfred B Tiono and Tran Thanh Duong and Ghyslain Mombo-Ngoma and Marielle Bouyou-Akotet and Halidou Tinto and Quique Bassat and Saadou Issifou and Marc Adamy and Helen Demarest and Stephan Duparc and Didier Leroy and Bart E Laurijssens and Sophie Biguenet and Afizi Kibuuka and Antoinette Kitoto Tshefu and Melnick Smith and Chanelle Foster and Illse Leipoldt and Peter G Kremsner and Bui Quang Phuc and Alphonse Ouedraogo and Michael Ramharter and OZ-Piperaquine Study Group},
doi = {10.1186/s12916-017-0940-3},
issn = {1741-7015},
year = {2017},
date = {2017-10-01},
urldate = {2017-10-01},
journal = {BMC Med.},
volume = {15},
number = {1},
pages = {181},
abstract = {BACKGROUND: The clinical development of a single encounter
treatment for uncomplicated malaria has the potential to
significantly improve the effectiveness of antimalarials.
Exploratory data suggested that the combination of artefenomel
and piperaquine phosphate (PQP) has the potential to achieve
satisfactory cure rates as a single dose therapy. The primary
objective of the study was to determine whether a single dose of
artefenomel (800 mg) plus PQP in ascending doses is an
efficacious treatment for uncomplicated Plasmodium falciparum
malaria in the 'target' population of children $\leq$ 5 years of
age in Africa as well as Asian patients of all ages. METHODS:
Patients in six African countries and in Vietnam were randomised
to treatment with follow-up for 42-63 days. Efficacy,
tolerability, safety and pharmacokinetics were assessed.
Additional key objectives were to characterise the
exposure-response relationship for polymerase chain reaction
(PCR)-adjusted adequate clinical and parasitological response at
day 28 post-dose (ACPR28) and to further investigate Kelch13 mutations. Patients in Africa (n = 355) and Vietnam (n = 82) were
included, with 85% of the total population being children 95%
PCR-adjusted ACPR at day 28. Achieving very high efficacy
following single dose treatment is challenging, since \> 95% of
the population must have sufficient concentrations to achieve
cure across a range of parasite sensitivities and baseline
parasitaemia levels. While challenging, the development of tools
suitable for deployment as single encounter curative treatments
for adults and children in Africa and to support elimination
strategies remains a key development goal. TRIAL REGISTRATION:
ClinicalTrials.gov, NCT02083380 . Registered on 7 March 2014.},
keywords = {Artefenomel; Children; Dose-response; OZ439; Pharmacokinetics; Phase II B; Piperaquine; Single dose combination treatment; Uncomplicated Plasmodium falciparum malaria; modelling and simulation},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The clinical development of a single encounter
treatment for uncomplicated malaria has the potential to
significantly improve the effectiveness of antimalarials.
Exploratory data suggested that the combination of artefenomel
and piperaquine phosphate (PQP) has the potential to achieve
satisfactory cure rates as a single dose therapy. The primary
objective of the study was to determine whether a single dose of
artefenomel (800 mg) plus PQP in ascending doses is an
efficacious treatment for uncomplicated Plasmodium falciparum
malaria in the ‘target’ population of children $łeq$ 5 years of
age in Africa as well as Asian patients of all ages. METHODS:
Patients in six African countries and in Vietnam were randomised
to treatment with follow-up for 42-63 days. Efficacy,
tolerability, safety and pharmacokinetics were assessed.
Additional key objectives were to characterise the
exposure-response relationship for polymerase chain reaction
(PCR)-adjusted adequate clinical and parasitological response at
day 28 post-dose (ACPR28) and to further investigate Kelch13 mutations. Patients in Africa (n = 355) and Vietnam (n = 82) were
included, with 85% of the total population being children 95%
PCR-adjusted ACPR at day 28. Achieving very high efficacy
following single dose treatment is challenging, since > 95% of
the population must have sufficient concentrations to achieve
cure across a range of parasite sensitivities and baseline
parasitaemia levels. While challenging, the development of tools
suitable for deployment as single encounter curative treatments
for adults and children in Africa and to support elimination
strategies remains a key development goal. TRIAL REGISTRATION:
ClinicalTrials.gov, NCT02083380 . Registered on 7 March 2014. |
