Hawkes M, Conroy AL, Kain KC, 2014. Spread of artemisinin resistance in malaria. N Engl J Med 371: 1944ā1945.
Biot C, Nosten F, Fraisse L, Ter-Minassian D, Khalife J, Dive D, 2011. The antimalarial ferroquine: from bench to clinic. Parasite 18: 207ā214.
Atteke C, Ndong JM, Aubouy A, Maciejewski L, Brocard J, LĆ©bibi J, Deloron P, 2003. In vitro susceptibility to a new antimalarial organometallic analogue, ferroquine, of Plasmodium falciparum isolates from the Haut-Ogooue region of Gabon. J Antimicrob Chemother 51: 1021ā1024.
Barends M, Jaidee A, Khaohirun N, Singhasivanon P, Nosten F, 2007. In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border. Malar J 6: 81.
Eyase FL, Akala HM, Johnson JD, Walsh DS, 2011. Inhibitory activity of ferroquine, versus chloroquine, against western Kenya Plasmodium falciparum field isolates determined by a SYBR Green I in vitro assay. Am J Trop Med Hyg 85: 984ā988.
Kreidenweiss A, Kremsner PG, Dietz K, Mordmuller B, 2006. In vitro activity of ferroquine (SAR97193) is independent of chloroquine resistance in Plasmodium falciparum. Am J Trop Med Hyg 75: 1178ā1181.
Held J, Supan C, Salazar CL, Tinto H, Bonkian LN, Nahum A, Moulero B, SiĆ© A, Coulibaly B, Sirima SB, Siribie M, Otsyula N, Otieno L, Abdallah AM, Kimutai R, Bouyou-Akotet M, Kombila M, Koiwai K, Cantalloube C, Din-Bell C, Djeriou E, Waitumbi J, Mordmüller B, Ter-Minassian D, Lell B, Kremsner PG, 2015. Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study. Lancet Infect Dis 15: 1409ā1419.
Wani WA, Jameel E, Baig U, Mumtazuddin S, Hun LT, 2015. Ferroquine and its derivatives: new generation of antimalarial agents. Eur J Med Chem 101: 534ā551.
Wells TN, Hooft van Huijsduijnen R, 2015. Ferroquine: welcome to the next generation of antimalarials. Lancet Infect Dis 15: 1365ā1366.
Mombo-Ngoma G, Supan C, Dal-Bianco MP, Missinou MA, Matsiegui PB, Ospina Salazar CL, Issifou S, Ter-Minassian D, Ramharter M, Kombila M, Kremsner PG, Lell B, 2011. Phase I randomized dose-ascending placebo-controlled trials of ferroquineāa candidate anti-malarial drugāin adults with asymptomatic Plasmodium falciparum infection. Malar J 10: 53.
Supan C, Mombo-Ngoma G, Dal-Bianco MP, Ospina Salazar CL, Issifou S, Mazuir F, Filali-Ansary A, Biot C, Ter-Minassian D, Ramharter M, Kremsner PG, Lell B, 2012. Pharmacokinetics of ferroquine, a novel 4-aminoquinoline, in asymptomatic carriers of Plasmodium falciparum infections. Antimicrob Agents Chemother 56: 3165ā3173.
Navarro VJ, Senior JR, 2006. Drug-related hepatotoxicity. N Engl J Med 354: 731ā739.
Common Toxicity Criteria for Adverse Events, version 4.0 (CTCAEv4): National Cancer Institute, National Institutes of Health, Bethesda, MD.
Manning J, Vanachayangkul P, Lon C, Spring M, So M, Sea D, Se Y, Somethy S, Phann ST, Chann S, Sriwichai S, Buathong N, Kuntawunginn W, Mitprasat M, Siripokasupkul R, Teja-Isavadharm P, Soh E, Timmermans A, Lanteri C, Kaewkungwal J, Auayporn M, Tang D, Chour CM, Prom S, Haigney M, Cantilena L, Saunders D, 2014. Randomized, double-blind, placebo-controlled clinical trial of a two-day regimen of dihydroartemisinin-piperaquine for malaria prevention halted for concern over prolonged corrected QT interval. Antimicrob Agents Chemother 58: 6056ā6067.
Atterhog JH, Malmberg P, 1981. Prevalence of primary T-wave changes in young men and their relationship to psychological and anthropometric data. Clin Cardiol 4: 91ā97.
Vandenberk B, Vandael E, Robyns T, Vandenberghe J, Garweg C, Foulon V, Ector J, Willems R, 2016. Which QT correction formulae to use for QT monitoring? J Am Heart Assoc 5: pii: e003264.
Moorman AC, Drobenuic J, Kamili S, 2017. Prevalence of false-positive hepatitis C antibody results, National Health and Nutrition Examination Study (NHANES) 2007ā2012. J Clin Virol 89: 1ā4.
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Artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated Plasmodium falciparum malaria. Ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (AS). We did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three African hospitals: two Gabonese and one Kenyan. We recruited adult men with symptomatic uncomplicated P. falciparum monoinfection. Four escalating doses of ferroquine (100, 200, 400, and 600 mg) were assessed in sequence, versus an amodiaquine comparator. After a 2:1 randomization (block size three, equating to N = 12 for each ferroquine dose and N = 6 for each of four amodiaquine comparator groups) patients received daily for three consecutive days, either ferroquine + AS (200 mg/day) or amodiaquine (612 mg/day) + AS (200 mg/day). Safety, electrocardiograms, parasite clearance times, efficacy, and pharmacokinetics were assessed to day 28. Seventy-two patients were randomized. Ferroquine + AS showed generally mild increases (Grade 1 toxicity) in alanine aminotransferase (ALT) levels with a dose trend starting at 400 mg. There were two Grade 2 ALT events: one patient receiving 200 mg (3.8 upper limit of normal [ULN], day 7) and one receiving 600 mg (3.3 ULN, day 14), both without increased bilirubin. One ferroquine 100 mg + AS patient after one dose was withdrawn after developing a QTcF interval prolongation > 60 milliseconds over baseline. Parasitemias in all patients cleared quickly, with no recurrence through day 28. Hepatic, as well as cardiac, profiles should be monitored closely in future trials. (ClinicalTrials.gov: NCT00563914)
Authorsā addresses: Christian Supan, Ghyslain Mombo-Ngoma, Carmen L. Ospina Salazar, Jana Held, Bertrand Lell, and Peter G. Kremsner, Centre de Recherches MĆ©dicales de LambarĆ©nĆ©, HĆ“pital Albert Schweitzer, LambarĆ©nĆ©, Gabon, and Institut für Tropenmedizin, Eberhard Karls UniversitƤt Tübingen, Tübingen, Germany, E-mails: christian.supan@outlook.com, ghyslain.mombongoma@gmail.com, carmenlucelly@outlook.com, janaheld@hotmail.de, bertrand.lell@gmail.com, and peter.kremsner@uni-tuebingen.de. Maryvonne Kombila, DĆ©partement de Parasitologie-Mycologie, FacultĆ© de MĆ©decine, UniversitĆ© des Sciences de la SantĆ©, Libreville, Gabon, E-mail: kombila.maryvonne@gmail.com. Cathy Cantalloube and Elhadj Djeriou, Sanofi-Aventis, Paris, France, E-mails: cathy.cantalloube@sanofi.com and elhadj.djeriou@sanofi.com. Bernhards Ogutu, John Waitumbi, Nekoye Otsula, Duncan Apollo, Mark E. Polhemus, and Douglas S. Walsh, Walter Reed Project (Kisumu), U.S. Army Medical Research Unit (USAMRU)-Kenya, Kenya Medical Research Institute, Nairobi, Kenya, E-mails: bernhards.ogutu@usamru-k.org, jwaitumbi@gmail.com, nekoye.otsula@usamru-k.org, duncan.otieno.apollo@gmail.com, polhemum@upstate.edu, and dsw518@yahoo.com.
Financial support: This work was supported by Sanofi-Aventis.
Conflicts of interest: Cathy Cantalloube and Elhadj Djeriou are employees of Sanofi-Aventis. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors may consider relevant to the content of the manuscript have been disclosed.
Hawkes M, Conroy AL, Kain KC, 2014. Spread of artemisinin resistance in malaria. N Engl J Med 371: 1944ā1945.
Biot C, Nosten F, Fraisse L, Ter-Minassian D, Khalife J, Dive D, 2011. The antimalarial ferroquine: from bench to clinic. Parasite 18: 207ā214.
Atteke C, Ndong JM, Aubouy A, Maciejewski L, Brocard J, LĆ©bibi J, Deloron P, 2003. In vitro susceptibility to a new antimalarial organometallic analogue, ferroquine, of Plasmodium falciparum isolates from the Haut-Ogooue region of Gabon. J Antimicrob Chemother 51: 1021ā1024.
Barends M, Jaidee A, Khaohirun N, Singhasivanon P, Nosten F, 2007. In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border. Malar J 6: 81.
Eyase FL, Akala HM, Johnson JD, Walsh DS, 2011. Inhibitory activity of ferroquine, versus chloroquine, against western Kenya Plasmodium falciparum field isolates determined by a SYBR Green I in vitro assay. Am J Trop Med Hyg 85: 984ā988.
Kreidenweiss A, Kremsner PG, Dietz K, Mordmuller B, 2006. In vitro activity of ferroquine (SAR97193) is independent of chloroquine resistance in Plasmodium falciparum. Am J Trop Med Hyg 75: 1178ā1181.
Held J, Supan C, Salazar CL, Tinto H, Bonkian LN, Nahum A, Moulero B, SiĆ© A, Coulibaly B, Sirima SB, Siribie M, Otsyula N, Otieno L, Abdallah AM, Kimutai R, Bouyou-Akotet M, Kombila M, Koiwai K, Cantalloube C, Din-Bell C, Djeriou E, Waitumbi J, Mordmüller B, Ter-Minassian D, Lell B, Kremsner PG, 2015. Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study. Lancet Infect Dis 15: 1409ā1419.
Wani WA, Jameel E, Baig U, Mumtazuddin S, Hun LT, 2015. Ferroquine and its derivatives: new generation of antimalarial agents. Eur J Med Chem 101: 534ā551.
Wells TN, Hooft van Huijsduijnen R, 2015. Ferroquine: welcome to the next generation of antimalarials. Lancet Infect Dis 15: 1365ā1366.
Mombo-Ngoma G, Supan C, Dal-Bianco MP, Missinou MA, Matsiegui PB, Ospina Salazar CL, Issifou S, Ter-Minassian D, Ramharter M, Kombila M, Kremsner PG, Lell B, 2011. Phase I randomized dose-ascending placebo-controlled trials of ferroquineāa candidate anti-malarial drugāin adults with asymptomatic Plasmodium falciparum infection. Malar J 10: 53.
Supan C, Mombo-Ngoma G, Dal-Bianco MP, Ospina Salazar CL, Issifou S, Mazuir F, Filali-Ansary A, Biot C, Ter-Minassian D, Ramharter M, Kremsner PG, Lell B, 2012. Pharmacokinetics of ferroquine, a novel 4-aminoquinoline, in asymptomatic carriers of Plasmodium falciparum infections. Antimicrob Agents Chemother 56: 3165ā3173.
Navarro VJ, Senior JR, 2006. Drug-related hepatotoxicity. N Engl J Med 354: 731ā739.
Common Toxicity Criteria for Adverse Events, version 4.0 (CTCAEv4): National Cancer Institute, National Institutes of Health, Bethesda, MD.
Manning J, Vanachayangkul P, Lon C, Spring M, So M, Sea D, Se Y, Somethy S, Phann ST, Chann S, Sriwichai S, Buathong N, Kuntawunginn W, Mitprasat M, Siripokasupkul R, Teja-Isavadharm P, Soh E, Timmermans A, Lanteri C, Kaewkungwal J, Auayporn M, Tang D, Chour CM, Prom S, Haigney M, Cantilena L, Saunders D, 2014. Randomized, double-blind, placebo-controlled clinical trial of a two-day regimen of dihydroartemisinin-piperaquine for malaria prevention halted for concern over prolonged corrected QT interval. Antimicrob Agents Chemother 58: 6056ā6067.
Atterhog JH, Malmberg P, 1981. Prevalence of primary T-wave changes in young men and their relationship to psychological and anthropometric data. Clin Cardiol 4: 91ā97.
Vandenberk B, Vandael E, Robyns T, Vandenberghe J, Garweg C, Foulon V, Ector J, Willems R, 2016. Which QT correction formulae to use for QT monitoring? J Am Heart Assoc 5: pii: e003264.
Moorman AC, Drobenuic J, Kamili S, 2017. Prevalence of false-positive hepatitis C antibody results, National Health and Nutrition Examination Study (NHANES) 2007ā2012. J Clin Virol 89: 1ā4.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 26 | 26 | 3 |
Full Text Views | 463 | 120 | 0 |
PDF Downloads | 162 | 49 | 0 |