A Phase 3, Double-Blind, Randomized Study of Arterolane Maleate-Piperaquine Phosphate vs Artemether-Lumefantrine for Falciparum Malaria in Adolescent and Adult Patients in Asia and Africa

作者：Toure Offianan Andre; Valecha Neena^*; Tshefu Antoinette K; Thompson Ricardo; Krudsood Srivicha; Gaye Oumar; Rao Bappanaidu Hoigegudde Krishnamurthy; Sagara Issaka; Bose Tarit Kumar; Mohanty Sanjib; Rao Ballamudi Srinivas; Anvikar Anupkumar R; Mwapasa Victor; Noedl Harald; Arora Sudershan; Roy Arjun; Iyer Sunil S; Sharma Pradeep; Saha Nilanjan; Jalali Rajinder K

来源：Clinical Infectious Diseases, 2016, 62(8): 964-971.

DOI：10.1093/cid/ciw029

• artemisinin combination therapy
• arterolane maleate
• malaria
• fixed-dose combination
• once-daily dose

Background. Artemisinins, which are derived from plants, are subject to risk of supply interruption due to climatic changes. Consequently, an effort to identify a new synthetic antimalarial was initiated. A fixed-dose combination of arterolane maleate (AM), a new synthetic trioxolane, with piperaquine phosphate (PQP), a long half-life bisquinoline, was evaluated in patients with uncomplicated Plasmodium falciparum malaria.
Methods. In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12-65 years with P. falciparum monoinfection received either AM-PQP (714 patients) once daily or artemether-lumefantrine (A-L; 358 patients) twice daily for 3 days. All patients were followed up until day 42.
Results. Of the 714 patients in the AM-PQP group, 638 (89.4%) completed the study; of the 358 patients in the A-L group, 301 (84.1%) completed the study. In both groups, the polymerase chain reaction corrected adequate clinical and parasitological response (PCR-corrected ACPR) on day 28 in intent-to-treat (ITT) and per-protocol (PP) populations was 92.86% and 92.46% and 99.25% and 99.07%, respectively. The corresponding figures on day 42 in the ITT and PP populations were 90.48% and 91.34%, respectively. After adjusting for survival ITT, the PCR-corrected ACPR on day 42 was >98% in both groups. The overall incidence of adverse events was comparable.
Conclusions. AM-PQP showed comparable efficacy and safety to A-L in the treatment of uncomplicated P. falciparum malaria in adolescent and adult patients. AM-PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance.

• 出版日期2016-4-15