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
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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. / Mombo-Ngoma, Ghyslain; Remppis, Jonathan; Sievers, Moritz; Zoleko Manego, Rella; Endamne, Lilian; Kabwende, Lumeka; Veletzky, Luzia; Nguyen, The Trong; Groger, Mirjam; Lötsch, Felix; Mischlinger, Johannes; Flohr, Lena; Kim, Johanna; Cattaneo, Chiara; Hutchinson, David; Duparc, Stephan; Moehrle, Joerg; Velavan, Thirumalaisamy P; Lell, Bertrand; Ramharter, Michael; Adegnika, Ayola Akim; Mordmüller, Benjamin; Kremsner, Peter G.
In: CLIN INFECT DIS, Vol. 66, No. 12, 01.06.2018, p. 1823-1830.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Mombo-Ngoma, Ghyslain
AU - Remppis, Jonathan
AU - Sievers, Moritz
AU - Zoleko Manego, Rella
AU - Endamne, Lilian
AU - Kabwende, Lumeka
AU - Veletzky, Luzia
AU - Nguyen, The Trong
AU - Groger, Mirjam
AU - Lötsch, Felix
AU - Mischlinger, Johannes
AU - Flohr, Lena
AU - Kim, Johanna
AU - Cattaneo, Chiara
AU - Hutchinson, David
AU - Duparc, Stephan
AU - Moehrle, Joerg
AU - Velavan, Thirumalaisamy P
AU - Lell, Bertrand
AU - Ramharter, Michael
AU - Adegnika, Ayola Akim
AU - Mordmüller, Benjamin
AU - Kremsner, Peter G
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1093/cid/cix1122
DO - 10.1093/cid/cix1122
M3 - SCORING: Journal article
C2 - 29293893
VL - 66
SP - 1823
EP - 1830
JO - CLIN INFECT DIS
JF - CLIN INFECT DIS
SN - 1058-4838
IS - 12
ER -
