Phase 2 efficacy trial of an oral 8-aminoquinoline (WR6026) for treatment of visceral leishmaniasis.

The efficacy of an oral 8-aminoquinoline (8-[[6-(diethylamino)hexyl]amino]-6-methoxy-4-methylquinoline) (WR6026) in the treatment of 16 patients with kala azar was evaluated. The first 8 patients received therapy for 2 weeks at a dosage of 0.75-1.00 mg/(kg.d); 1 patient was cured, and in regard to the other 7, a 1-logarithm decrease in the number of splenic parasites and clinical improvement were noted. The next 8 patients received therapy for 4 weeks at the same daily dosage (1 mg/[kg.d]); 4 were cured, and for the other 4, 1- to 2-log decreases in the number of parasites and clinical improvement (in regard to weight, liver and spleen size, hemoglobin level, and leukocyte count) were noted. The therapy was associated with minimal toxicity; adverse effects included gastrointestinal distress, headache, and methemoglobinemia. The fact that one-half of the patients were cured indicates that future trials with longer regimens and higher dosages are warranted and should include patients for whom existing treatment methods have failed.