Artemisinin-naphthoquine combination (ARCO™) therapy for uncomplicated falciparum malaria in adults of Papua New Guinea: A preliminary report on safety and efficacy

Abstract

Background: The use of anti-malarial drug combinations with artemisinin or with one of its derivatives is now widely recommended to overcome drug resistance in falciparum as well as vivax malaria. The fixed oral dose artemisinin-naphthoquine combination (ANQ, ARCO™) is a newer artemisinin-based combination (ACT) therapy undergoing clinical assessment. A study was undertaken to assess the safety, efficacy and tolerability of ANQ combination in areas of multi-drug resistance to generate preliminary baseline data in adult population of Papua New Guinea.

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

“…NQ combined with artemisinin derivatives has achieved adequate clinical efficacy against falciparum malaria (11)(12)(13), as well as against CQ-sensitive and CQ-resistant vivax malaria (14)(15)(16). However, concerns have been raised that the currently available single-dose regimen (ARCO) provides inadequate reduction of the early parasite biomass, leaving the more slowly eliminated NQ vulnerable to the selection of drug resistance.…”

“…NQ has been combined with artemisinin as a fixed-dose combination therapy (ARCO) with proven in vivo efficacy against falciparum (11)(12)(13) and vivax malaria (14)(15)(16). Although approved and registered in more than 10 countries, in vitro NQ susceptibility data in clinical isolates of P. falciparum are limited, with no published ex vivo data yet available for P. vivax.…”

Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Tolerability, Safety, and Preliminary Efficacy Study

“…Although ART has been studied relatively extensively, there are few safety data on NQ. Available data from healthy volunteers (24) and clinical studies (9,10,28) suggest that the drug is safe apart from short-lived abdominal distension (28), occasional mild and transient elevations in serum ALT concentrations that appear unrelated to the dose (24), one episode of hypoglycemia and associated psychiatric disturbance in a Papua New Guinean adult with uncomplicated malaria treated with ART-NQ (10), and dizziness (which was relieved by oral glucose) in two Chinese adults who received ART-NQ (26). We found no evidence that NQ in combination with ART was hepatotoxic at the recommended doses, and none of our children developed hypoglycemia.…”

“…Artesunate-pyronaridine appears promising in early-phase trials but is not yet available in tropical countries (20). Despite limited published pharmacologic and efficacy data (9,10,28) and the recommendation that it be used as single-dose treatment (13), ART-NQ is currently marketed as the fixed coformulation ARCO (Kunming Pharmaceuticals, Kunming, China) in Oceanic countries, including Papua New Guinea, and also in parts of sub-Saharan Africa (9). It has yet to achieve WHO prequalification status.…”

“…It has been given as singleand two-dose monotherapy (28), in combination with dihydroartemisinin and trimethoprim in a two-dose regimen (12), and, most recently, combined with ART as either a single-or a twodose treatment (9). Apart from one Indonesian study with a 28-day adequate clinical and parasitologic response rate (ACPR) of 79% in mixed P. falciparum-P. vivax infections, the ACPRs for NQ given alone and as part of combination therapy for uncomplicated P. falciparum or P. vivax malaria have been Ն94% at doses of 8 to 16 mg/kg of body weight (9,10,28).…”