Arterolane, a New Synthetic Trioxolane for Treatment of Uncomplicated Plasmodium falciparum Malaria: A Phase II, Multicenter, Randomized, Dose-Finding Clinical Trial

Background
Drug‐resistant Plasmodium falciparum malaria necessitates development of novel drugs for treatment. The present study assessed the efficacy and safety of 3 dose levels of arterolane (RBx 11160), a synthetic trioxolane, for treatment of acute uncomplicated falciparum malaria.
 
Methods
In this randomized, double‐blind, multicenter, parallel‐group, dose‐finding, phase II trial, 230 patients from 4 centers in Thailand, India, and Tanzania (mainland and Zanzibar) received either 50 mg ( ), 100 mg ( ), or 200 mg ( ) of arterolane once daily for 7 days. Patients (aged 13–65 years) with asexual parasite density of 1000–100,000 parasites/μL were included and were followed up for 28 days. The median time to 90% parasite clearance (PC90) was evaluated.
 
Results
The median PC90 was longer in the group receiving the 50‐mg dose (19.4 h), compared with the groups receiving the 100‐mg dose (12.8 h) and 200‐mg dose (12.6 h) ( ). The polymerase chain reaction–corrected adequate clinical and parasitological responses on day 28 were 63%, 71%, and 72% for the groups receiving the 50‐mg, 100‐mg, and 200‐mg doses, respectively, by intention‐to‐treat analysis (odds ratio, 1.55; 95% confidence interval, 0.78–3.06, for comparison of the 200‐mg and 50‐mg dose groups). Treatment was generally well tolerated. No patient died or experienced any serious adverse event. Mild complaints were reported in <10% of the patients and were similar in the 3 groups. Biochemistry and hematological analyses did not show any sign of drug toxicity in any patient.
 
Conclusion
Arterolane at daily doses of 100 and 200 mg is a rapidly acting, effective, and safe synthetic antimalarial drug, which may potentially represent an alternative to artemisinin derivatives in antimalarial combination therapy.