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.
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