Spiroindolone KAE609 for falciparum and vivax malaria

New England Journal of Medicine

Volumn 371, Issue 5, 2014, Pages 403-410

  White, Nicholas J ^a,c   Pukrittayakamee, Sasithon ^a   Phyo, Aung Pyae ^a   Rueangweerayut, Ronnatrai ^b   Nosten, François ^a,c   Jittamala, Podjanee ^a   Jeeyapant, Atthanee ^a   Jain, Jay Prakash ^d   Lefèvre, Gilbert ^e   Li, Ruobing ^f   Magnusson, Baldur ^e   Diagana, Thierry T ^g   Leong, F Joel ^g  

^a MAHIDOL UNIVERSITY   (Thailand)

^b MAE SOT GENERAL HOSPITAL   (Thailand)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d NOVARTIS HEALTHCARE PVT LTD   (India)

^e NOVARTIS PHARMA AG   (Switzerland)

^f Laboratory of Immunology   (China)

^g NOVARTIS INSTITUTE FOR TROPICAL DISEASES   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ARTESUNATE PLUS MEFLOQUINE; ASPARTATE AMINOTRANSFERASE; CHLOROQUINE PLUS PRIMAQUINE; CIPARGAMIN; KAE 609; PARACETAMOL; UNCLASSIFIED DRUG;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANOREXIA; ANTIMALARIAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; DISEASE SEVERITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; FEMALE; FEVER; GLUCOSURIA; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYPERGLYCEMIA; LIMIT OF QUANTITATION; MALARIA FALCIPARUM; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; NAUSEA; PARASITE CLEARANCE; PHASE 2 CLINICAL TRIAL; PLASMODIUM VIVAX MALARIA; PRIORITY JOURNAL; QT INTERVAL; TANDEM MASS SPECTROMETRY; THAILAND; TIME TO MAXIMUM PLASMA CONCENTRATION; TYPHOID FEVER; VOMITING;

ADMINISTRATION, ORAL; ADULT; ANTIMALARIALS; AREA UNDER CURVE; FEMALE; HUMANS; INDOLES; MALARIA, FALCIPARUM; MALARIA, VIVAX; MALE; MIDDLE AGED; NAUSEA; PARASITE LOAD; PARASITEMIA; PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; SPIRO COMPOUNDS; THAILAND; YOUNG ADULT;

EID: 84904909454     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1315860     Document Type: Article

References (15)

1. Malaria: fact sheet no. 94. Geneva: World Health Organization (http://www.who.int/mediacentre/factsheets/fs094/en/#).
2. Dondorp AM, Nosten F, Yi P, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2009;361:455-67. [Erratum, N Engl J Med 2009;361:1714.]
3. Phyo AP, Nkhoma S, Stepniewska K, et al. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 2012;379:1960-6.
4. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 2008;359:2619-20.
5. Ariey F, Witkowski B, Amaratunga C, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 2014;505:50-5.
6. Wells TNC, Alonso PL, Gutteridge WE. New medicines to improve control and contribute to the eradication of malaria. Nat Rev Drug Discov 2009;8:879-91.
7. Yeung BK, Zou B, Rottmann M, et al. Spirotetrahydro beta-carbolines (spiroindolones): a new class of potent and orally efficacious compounds for the treatment of malaria. J Med Chem 2010;53:5155-64.
8. Rottmann M, McNamara C, Yeung BKS, et al. Spiroindolones, a potent compound class for the treatment of malaria. Science 2010;329:1175-80.
9. +) regulation in the malaria parasite Plasmodium falciparum involves the cation ATPase PfATP4 and is a target of the spiroindolone antimalarials. Cell Host Microbe 2013;13:227-37.
10. van Pelt-Koops JC, Pett HE, Graumans W, et al. The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector. Antimicrob Agents Chemother 2012;56:3544-8.
11. Guidelines for the treatment of malaria. 2nd ed. Geneva: World Health Organization, 2010 (http://whqlibdoc.who.int/publications/2010/9789241547925- eng.pdf).
12. Flegg JA, Guerin PJ, White NJ, Stepniewska K. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J 2011;10:339.
13. White NJ. Antimalarial pharmacokinetics and treatment regimens. Br J Clin Pharmacol 1992;34:1-10.
14. Pukrittayakamee S, Chantra A, Simpson JA, et al. Therapeutic responses to different antimalarial drugs in vivax malaria. Antimicrob Agents Chemother 2000;44:1680-5. (Pubitemid 30340814)
15. White NJ. The parasite clearance curve. Malar J 2011;10:278.