ProCite
RefWorks
Reference Manager
BibTeX
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EndNote
-
1.
Hawkes M, Conroy AL, Kain KC, 2014. Spread of artemisinin resistance in malaria. N Engl J Med 371: 1944–1945.
-
2.
Biot C, Nosten F, Fraisse L, Ter-Minassian D, Khalife J, Dive D, 2011. The antimalarial ferroquine: from bench to clinic. Parasite 18: 207–214.
-
3.
Atteke C, Ndong JM, Aubouy A, Maciejewski L, Brocard J, Lébibi 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: 1021–1024.
-
4.
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.
-
5.
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: 984–988.
-
6.
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: 1178–1181.
-
7.
Held J, Supan C, Salazar CL, Tinto H, Bonkian LN, Nahum A, Moulero B, Sié 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: 1409–1419.
-
8.
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: 534–551.
-
9.
Wells TN, Hooft van Huijsduijnen R, 2015. Ferroquine: welcome to the next generation of antimalarials. Lancet Infect Dis 15: 1365–1366.
-
10.
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 ferroquine—a candidate anti-malarial drug—in adults with asymptomatic Plasmodium falciparum infection. Malar J 10: 53.
-
11.
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: 3165–3173.
-
12.
Navarro VJ, Senior JR, 2006. Drug-related hepatotoxicity. N Engl J Med 354: 731–739.
-
13.
Common Toxicity Criteria for Adverse Events, version 4.0 (CTCAEv4): National Cancer Institute, National Institutes of Health, Bethesda, MD.
-
14.
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: 6056–6067.
-
15.
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: 91–97.
-
16.
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.
-
17.
Moorman AC, Drobenuic J, Kamili S, 2017. Prevalence of false-positive hepatitis C antibody results, National Health and Nutrition Examination Study (NHANES) 2007–2012. J Clin Virol 89: 1–4.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 533 | 495 | 79 |
| Full Text Views | 487 | 20 | 0 |
| PDF Downloads | 170 | 8 | 0 |
Phase 2a, Open-Label, 4-Escalating-Dose, Randomized Multicenter Study Evaluating the Safety and Activity of Ferroquine (SSR97193) Plus Artesunate, versus Amodiaquine Plus Artesunate, in African Adult Men with Uncomplicated Plasmodium falciparum Malaria
Christian Supan
Christian Supan
Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer, Lambaréné, Gabon;
Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Ghyslain Mombo-Ngoma
Ghyslain Mombo-Ngoma
Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer, Lambaréné, Gabon;
Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Maryvonne Kombila
Maryvonne Kombila
Département de Parasitologie-Mycologie, Faculté de Médecine, Université des Sciences de la Santé, Libreville, Gabon;
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Carmen L. Ospina Salazar
Carmen L. Ospina Salazar
Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer, Lambaréné, Gabon;
Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Jana Held
Jana Held
Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer, Lambaréné, Gabon;
Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Bertrand Lell
Bertrand Lell
Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer, Lambaréné, Gabon;
Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Cathy Cantalloube
Cathy Cantalloube
Sanofi-Aventis, Paris, France;
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Elhadj Djeriou
Elhadj Djeriou
Sanofi-Aventis, Paris, France;
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Bernhards Ogutu
Bernhards Ogutu
Walter Reed Project (Kisumu), U.S. Army Medical Research Unit (USAMRU)-Kenya, Kenya Medical Research Institute, Nairobi, Kenya
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John Waitumbi
John Waitumbi
Walter Reed Project (Kisumu), U.S. Army Medical Research Unit (USAMRU)-Kenya, Kenya Medical Research Institute, Nairobi, Kenya
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Nekoye Otsula
Nekoye Otsula
Walter Reed Project (Kisumu), U.S. Army Medical Research Unit (USAMRU)-Kenya, Kenya Medical Research Institute, Nairobi, Kenya
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Duncan Apollo
Duncan Apollo
Walter Reed Project (Kisumu), U.S. Army Medical Research Unit (USAMRU)-Kenya, Kenya Medical Research Institute, Nairobi, Kenya
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Mark E. Polhemus
Mark E. Polhemus
Walter Reed Project (Kisumu), U.S. Army Medical Research Unit (USAMRU)-Kenya, Kenya Medical Research Institute, Nairobi, Kenya
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Peter G. Kremsner
Peter G. Kremsner
Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer, Lambaréné, Gabon;
Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany;
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Douglas S. Walsh
Douglas S. Walsh
Walter Reed Project (Kisumu), U.S. Army Medical Research Unit (USAMRU)-Kenya, Kenya Medical Research Institute, Nairobi, Kenya
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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)
- Supplemental Materials (PDF 297 KB)
Author Notes
Authors’ addresses: Christian Supan, Ghyslain Mombo-Ngoma, Carmen L. Ospina Salazar, Jana Held, Bertrand Lell, and Peter G. Kremsner, Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer, Lambaréné, Gabon, and Institut für Tropenmedizin, Eberhard Karls Universität 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, Département de Parasitologie-Mycologie, Faculté de Médecine, Université des Sciences de la Santé, 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.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Hawkes M, Conroy AL, Kain KC, 2014. Spread of artemisinin resistance in malaria. N Engl J Med 371: 1944–1945.
-
2.
Biot C, Nosten F, Fraisse L, Ter-Minassian D, Khalife J, Dive D, 2011. The antimalarial ferroquine: from bench to clinic. Parasite 18: 207–214.
-
3.
Atteke C, Ndong JM, Aubouy A, Maciejewski L, Brocard J, Lébibi 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: 1021–1024.
-
4.
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.
-
5.
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: 984–988.
-
6.
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: 1178–1181.
-
7.
Held J, Supan C, Salazar CL, Tinto H, Bonkian LN, Nahum A, Moulero B, Sié 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: 1409–1419.
-
8.
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: 534–551.
-
9.
Wells TN, Hooft van Huijsduijnen R, 2015. Ferroquine: welcome to the next generation of antimalarials. Lancet Infect Dis 15: 1365–1366.
-
10.
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 ferroquine—a candidate anti-malarial drug—in adults with asymptomatic Plasmodium falciparum infection. Malar J 10: 53.
-
11.
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: 3165–3173.
-
12.
Navarro VJ, Senior JR, 2006. Drug-related hepatotoxicity. N Engl J Med 354: 731–739.
-
13.
Common Toxicity Criteria for Adverse Events, version 4.0 (CTCAEv4): National Cancer Institute, National Institutes of Health, Bethesda, MD.
-
14.
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: 6056–6067.
-
15.
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: 91–97.
-
16.
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.
-
17.
Moorman AC, Drobenuic J, Kamili S, 2017. Prevalence of false-positive hepatitis C antibody results, National Health and Nutrition Examination Study (NHANES) 2007–2012. J Clin Virol 89: 1–4.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 533 | 495 | 79 |
| Full Text Views | 487 | 20 | 0 |
| PDF Downloads | 170 | 8 | 0 |