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 (n=78), 100mg (n=76), or 200 mg (n=76) of arterolane once daily for 7 days. Patients (aged 13-65 years) with asexual parasite density of 1000-100,000 parasites/microL 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) (P < .01). 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 signof drug toxicity in any patient.


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov identifier NCT00362050.
Valecha
Neena
N
National Institute of Malaria Research, Indian Council of Medical Research, Delhi, India. neenavalecha@gmail.com
Looareesuwan
Sornchai
S
Martensson
Andreas
A
Abdulla
Salim Mohammed
SM
Krudsood
Srivicha
S
Tangpukdee
Noppadon
N
Mohanty
Sanjib
S
Mishra
Saroj K
SK
Tyagi
P K
PK
Sharma
S K
SK
Moehrle
Joerg
J
Gautam
Anirudh
A
Roy
Arjun
A
Paliwal
Jyoti K
JK
Kothari
Monica
M
Saha
Nilanjan
N
Dash
Aditya P
AP
Björkman
Anders
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D007194:India; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010545:Peroxides / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000302:isolation & purification*; D013141:Spiro Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D013636:Tanzania; D013785:Thailand; D016896:Treatment Outcome; D055815:Young Adult
D000962:Antimalarials; D006573:Heterocyclic Compounds, 1-Ring; D010545:Peroxides; D013141:Spiro Compounds; C489136:arterolane