Universität zu Köln

Mombo-Ngoma, Ghyslain ORCID: 0000-0003-2658-8706, Remppis, Jonathan, Sievers, Moritz, Manego, Rella Zoleko, Endamne, Lilian, Kabwende, Lumeka, Veletzky, Luzia ORCID: 0000-0002-6136-8170, Groger, Mirjam ORCID: 0000-0001-7375-3685, Lotsch, Felix ORCID: 0000-0002-6938-9523, Mischlinger, Johannes ORCID: 0000-0002-2012-6327, Flohr, Lena, Kim, Johanna, Cattaneo, Chiara, Hutchinson, David, Duparc, Stephan ORCID: 0000-0002-9649-4847, Moehrle, Joerg, Velavan, Thirumalaisamy P., Lell, Bertrand, Ramharter, Michael ORCID: 0000-0002-9259-1885, Adegnika, Ayola Akim, Mordmueller, Benjamin and Kremsner, Peter G. (2018). Efficacy and Safety of Fosmidomycin-Piperaquine as Nonartemisinin-Based Combination Therapy for Uncomplicated Falciparum Malaria: A Single-Arm, Age De-escalation Proof-of-Concept Study in Gabon. Clin. Infect. Dis., 66 (12). S. 1823 - 1831. CARY: OXFORD UNIV PRESS INC. ISSN 1537-6591

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Abstract

Background. Fosmidomycin-piperaquine is being developed as nonartemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. Methods. The study was a phase 2, single-arm, proof-of-concept study of the efficacy, tolerability, and safety of fosmidomycin-piperaquine for the treatment of uncomplicated Plasmodium falciparum monoinfection in Gabon. Adults and children of both sexes with initial parasite counts between 1000 and 150 000/mu L received oral treatment with fosmidomycin (twice daily doses of 30 mg/kg) and piperaquine (once daily dose of 16 mg/kg) for 3 days and followed-up for 63 days. The primary efficacy endpoint was the per-protocol polymerase chain reaction (PCR)-corrected day 28 adequate clinical and parasitological response (ACPR). Results. One hundred patients were enrolled. The PCR-corrected day 28 ACPR rate was 83/83, or 100% (95% confidence interval, 96-100). Fourteen patients had asexual parasitaemia between day 28 and day 63; all were typed by PCR as new infections. Fosmidomycin-piperaquine therapy led to rapid parasite clearance (median, 36 hours; interquartile range [IQR], 6-60) and fever clearance time (median, 12 hours; IQR, 6-48). The electrocardiogram assessments showed 2 patients with prolonged QT interval >500 msec following study drug administration. The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity. Conclusions. This is the first report of the use of the combination fosmidomycin-piperaquine. The combination appeared to have high efficacy and be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval .

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mombo-Ngoma, Ghyslain UNSPECIFIED orcid.org/0000-0003-2658-8706 UNSPECIFIED Remppis, Jonathan UNSPECIFIED UNSPECIFIED UNSPECIFIED Sievers, Moritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Manego, Rella Zoleko UNSPECIFIED UNSPECIFIED UNSPECIFIED Endamne, Lilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Kabwende, Lumeka UNSPECIFIED UNSPECIFIED UNSPECIFIED Veletzky, Luzia UNSPECIFIED orcid.org/0000-0002-6136-8170 UNSPECIFIED Groger, Mirjam UNSPECIFIED orcid.org/0000-0001-7375-3685 UNSPECIFIED Lotsch, Felix UNSPECIFIED orcid.org/0000-0002-6938-9523 UNSPECIFIED Mischlinger, Johannes UNSPECIFIED orcid.org/0000-0002-2012-6327 UNSPECIFIED Flohr, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Johanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Cattaneo, Chiara UNSPECIFIED UNSPECIFIED UNSPECIFIED Hutchinson, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Duparc, Stephan UNSPECIFIED orcid.org/0000-0002-9649-4847 UNSPECIFIED Moehrle, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Velavan, Thirumalaisamy P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lell, Bertrand UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramharter, Michael UNSPECIFIED orcid.org/0000-0002-9259-1885 UNSPECIFIED Adegnika, Ayola Akim UNSPECIFIED UNSPECIFIED UNSPECIFIED Mordmueller, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kremsner, Peter G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-182817
DOI:	10.1093/cid/cix1122
Journal or Publication Title:	Clin. Infect. Dis.
Volume:	66
Number:	12
Page Range:	S. 1823 - 1831
Date:	2018
Publisher:	OXFORD UNIV PRESS INC
Place of Publication:	CARY
ISSN:	1537-6591
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANTIMALARIAL-DRUG; IN-VIVO; CLINDAMYCIN Multiple languages Immunology; Infectious Diseases; Microbiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18281