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Clin Infect Dis. 2018 Jun 1;66(12):1823-1830. doi: 10.1093/cid/cix1122.

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.

Author information

1
Centre de Recherches Médicales de Lambaréné, Libreville, Gabon.
2
Département de Parasitologie-Mycologie, Université des Sciences de la Santé, Libreville, Gabon.
3
Institute of Tropical Medicine, University of Tübingen, and German Centre for Infection Research, Hamburg, Germany.
4
DMG Deutsche Malaria GmbH, formerly Jomaa Pharma GmbH, Hamburg, Germany.
5
Medicines for Malaria Venture, Geneva, Switzerl.
6
Vietnamese-German Center for Medical Research, Hanoi and Faculty of Medicine, Duy Tan University DaNang, Vietnam.
7
Bernhard Nocht Hospital for Tropical Diseases, Bernhard Nocht Institute for Tropical Medicine and University Medical Center Hamburg-Eppendorf, Germany.

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 150000/µL 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. Clinical Trials Registration. NCT02198807.

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