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

Clin Infect Dis. 2016 Apr 15;62(8):964-971. doi: 10.1093/cid/ciw029.

Offianan Andre Toure ¹, Neena Valecha ², Antoinette K Tshefu ³, Ricardo Thompson ⁴, Srivicha Krudsood ⁵, Oumar Gaye ⁶, Bappanaidu Hoigegudde Krishnamurthy Rao ⁷, Issaka Sagara ⁸, Tarit Kumar Bose ⁹, Sanjib Mohanty ¹⁰, Ballamudi Srinivas Rao ¹¹, Anupkumar R Anvikar ², Victor Mwapasa ¹², Harald Noedl ¹³ ¹⁴, Sudershan Arora ¹⁵, Arjun Roy ¹⁶, Sunil S Iyer ¹⁷, Pradeep Sharma ¹⁷, Nilanjan Saha ¹⁸, Rajinder K Jalali ¹⁹, AM–PQP Study Team, Landry Tiacoh, Sonia Enosse, Noppadon Tangpukdee, Jack Kokolomami, Jean-Louis Ndiaye, Deepak Rao, Ntamabyaliro Nsengi Yumva, Bouran Sidibe, Rajesh Mohanty, A C Jha, Mulinda Nyirenda, Peter Starzengruber, Paul Swoboda

Affiliations

1 Malariology Department, Institut Pasteur Côte d'Ivoire, Abidjan.
2 Epidemiology and Clinical Research Division, National Institute of Malaria Research, New Delhi, India.
3 Centre de recherches cliniques et epidemiologiques de Mont Amba, Centre hospitalier de Mont Amba, Ecole de Sante Publique, Universite de Kinshasa, Democratic Republic of Congo.
4 Chókwè Health Research and Training Centre, Mozambique.
5 Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Thailand.
6 Department of Parasitology Guediawaye District Hospital, University Cheikh Anta Diop, Dakar Fann, Senegal.
7 Department of Medicine, Government Wenlock District Hospital, Mangalore, Karnataka, India.
8 Malaria Research and Training Center, University of Science, Techniques and Technologies Bamako, Mali.
9 Community Welfare Society Hospital, Jagda.
10 Ispat General Hospital, Rourkela, Odisha.
11 Department of Medicine, Tata Main Hospital, Jamshedpur, Jharkhand, India.
12 College of Medicine, Blantyre, Malawi.
13 Malaria Research Initiative Bandarban, Sadar District Hospital, Bangladesh.
14 Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Austria.
15 Corporate Office.
16 CDM & Biostatistics, Medical Affairs & Clinical Research.
17 Clinical Pharmacology & Pharmacokinetics.
18 Medical Global Marketing, Corporate Office.
19 Medical Affairs & Clinical Research, Sun Pharmaceutical Industries Limited (erstwhile Ranbaxy Laboratories Ltd), Gurgaon, Haryana, India.

PMID: 26908796 DOI: 10.1093/cid/ciw029

Abstract

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 uncomplicatedPlasmodium falciparummalaria.

Methods: In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12-65 years withP. falciparummonoinfection 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 uncomplicatedP. falciparummalaria in adolescent and adult patients. AM-PQP demonstrated high clinical and parasitological response rates as well as rapid Parasite clearance.

Clinical trials registration: India. CTRI/2009/091/000101.

Keywords

artemisinin combination therapy; arterolane maleate; fixed-dose combination; malaria; once-daily dose.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-10852A

Arterolane maleate

Antimalarial

Parasite

Infection

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