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Efficacy and Safety of Arterolane-piperaquine in the Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria in Adults: A Post Marketing Surveillance Study
Background and Objective: Arterolane maleate (150 mg) and Piperaquine phosphate (750 mg) as a fixed dose combination was approved for the eTreatment of acute uncomplicated malaria infections due to Plasmodium falciparum (P. falciparum) in adultsf. Arterolane is a synthetic trioxolane, which rapidly kills malarial parasites in blood and provides fast relief from symptoms of malaria like fever, chills and associated symptoms. Piperaquine has a long lasting effect than Arterolane and kills the residual malarial parasites. There was a need of a post marketing surveillance study to ascertain efficacy and to identify any safety concerns with the use of Arterolane- Piperaquine (AP) therapy in adult patients with uncomplicated P. falciparum malaria in India. Methods: This was a prospective, open-label, single arm, multi-center, post-marketing study. Patients with acute symptomatic uncomplicated malaria confirmed positive for P.falciparum malaria by Rapid Diagnostic Test (RDT) and presence of fever (. 99 ‹F) were included. Enrolled patients were on the study drug, Arterolane-Piperaquine therapy, one tablet once daily for 3 consecutive days. Patients with severe malaria, mixed infection, age 65 years, known allergy, significant renal or hepatic impairment; and pregnant and lactating women were excluded from the study. Efficacy was assessed in terms of percentage of patients being eafebrilef and blood smear negative for P. falciparum at end of 3 days of treatment and at the end of day 28 of the Observation period. Safety and tolerability was evaluated by the incidence and severity of adverse events (AEs), and abnormal laboratory values through the 3 days of treatment with AP therapy and day 28 of Observation period. Results: A total of 1681 patients were screened of which 336 patients were found to be febrile with RDT positive for P. falciparum and were enrolled in the study. Of the enrolled patients, 67.9% of patients were males and 32.1% were females, with the mean age of 33.0 years. In this study, the Primary Endpoint for the percentage of patients being eafebrilef at end of 3 days of treatment was almost 100%, confirming the efficacy of AP therapy. This was further confirmed by the absence of P. falciparum in thick blood smear examination at the end of 3 days of treatment. Regarding the Secondary Endpoint, 100% of patients were eaparasitemiaf on Day 28 of the observation period on thick blood smear examination; and there was no reported case of efeverf during 28 Days of the observation period. Arterolane-Piperaquine therapy was well tolerated and there was no new adverse event that was reported in this study compared to the earlier studies done with AP therapy. Conclusion: Arterolane-Piperaquine therapy provides rapid clearance of P. falciparum parasite, relief from most theramalaria related symptoms with good tolerability and patient compliance in acute uncomplicated falciparum malaria.
Act: Artemisinin-based Combination Therapies; Ap Therapy / Arterolane-piperaquine: Fixed Dose Combination of Arterolane Maleate (150 Mg) And Piperaquine Phosphate (750 Mg); Al Therapy: Artemether- Lumefantrine; Sp Therapy: Artesunate – Sulfadoxine And Pyrimethamine; P. Falciparum: Plasmodium Falciparum Malaria; Rdt: Rapid Diagnostic Test For Malaria
- WHO: World Malaria Report 2013; http://www.who.int/malaria/publications/world_malaria_report_2013/en/. Accessed on 20th May 2014.
- Dua B, Acharya A. Malaria: Current strategies for control in India. Indian Journal of Medical Specialities 2013; 4(1):59-66.
- Malaria: magnitude of the problem. National Vector Borne Disease Control Programme. Available at http://nvbdcp.gov.in/malaria3.html. Accessed on 20th May 2014.
- World Health Organization Guidelines for the Treatment of Malaria. Second Edition. World Health Organization. Available at: http://www.who.int/malaria/publications/atoz/9789241547925/en/index.html. Accessed on 20th May 2014.
- Vennerstrom JL, et al. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature 2004; 430: 900-904.
- Uhlemann AC et al. Mechanism of antimalarial action of the synthetic trioxolane RBX11160. Antimicrob Agents Chemother 2007; 51: 667-72.
- Valecha N et al. Arterolane, a new synthetic trioxolane for treatment of uncomplicated Plasmodium falciparum malaria. A phase II multicenter randomized, dose-finding clinical trial. Clin Inf Dis 2010; 51: 684-91.
- Valecha N, et al. Arterolane maleate plus piperaquine phosphate for treatment of uncomplicated Plasmodium falciparum malaria: a comparative, multicenter, randomized clinical trial. Clin Inf Dis 2012; 55:663-71.
- Fugi MA, et al. Probing the antimalarial mechanisms of artemisinin and 0Z277 (arterolane) with nonperoxide isosteres and nitroxyl radicals. Antimicrob Agents Chemother 2010; 54: 1042-6.
- Gautam A, et al. Pharmacokinetics and pharmacodynamics of arterolane maleate following multiple oral doses in adult patients with Plasmodium falciparum malaria. J Clin Pharmacol 2011; 51: 1519-28.
- Snyder C, et al. In vitro and in vivo interaction of synthetic peroxide RBx11160 (0Z277) with piperaquine in Plasmodium models. Exp Parasitol 2007; 115: 296-300.
- Diagnosis and treatment of malaria. National Vector Borne Disease Control Programme. Available at: http://www.nvbdcp.gov.in/. Accessed on 20th May 2014.
- White NJ, et al. Clinical pharmacokinetics and pharmacodynamics of artemether-lumefantrine. Clin Pharmacokinet 1999;37:105-125.
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