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
| Autor: | Cantalloube C, Bernhards Ogutu, Otsula N, Peter G. Kremsner, Apollo D, Walsh Ds, Elhadj Djeriou, Christian Supan, Ghyslain Mombo-Ngoma, John N. Waitumbi, Mark E. Polhemus, Bertrand Lell, Ospina Salazar Cl, Maryvonne Kombila, Jana Held |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Randomization Metallocenes 030231 tropical medicine 030106 microbiology Artesunate Amodiaquine Gastroenterology law.invention Antimalarials 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Randomized controlled trial Pharmacokinetics law Virology Internal medicine medicine Humans Ferrous Compounds Gabon Malaria Falciparum Artemisinin Aged Aged 80 and over Dose-Response Relationship Drug biology business.industry Plasmodium falciparum Articles Middle Aged biology.organism_classification Kenya Artemisinins Editorial Infectious Diseases chemistry Toxicity Aminoquinolines Drug Therapy Combination Parasitology business medicine.drug |
| Zdroj: | The American Journal of Tropical Medicine and Hygiene. 97:514-525 |
| ISSN: | 1476-1645 0002-9637 |
| DOI: | 10.4269/ajtmh.16-0731 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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