Randomized, double-blinded, phase 2 trial of WR 279,396 (paromomycin and gentamicin) for cutaneous leishmaniasis in Panama

Abstract

In this randomized, double-blinded Phase 2 trial, 30 patients with Leishmania panamensis cutaneous leishmaniasis were randomly allocated (1:1) to receive once daily topical treatment with WR 279,396 (15% paromomycin + 0.5% gentamicin) or Paromomycin Alone (15% paromomycin) for 20 days. The index lesion cure rate after 6 months follow-up was 13 of 15 (87%) for WR 279,396 and 9 of 15 (60%) for Paromomycin Alone (P = 0.099). When all treated lesions were included, the final cure rate for WR 279,398-treated patients was again 87%, but the final cure rate for Paromomycin Alone-treated patients was 8 of 15 (53.3%; P = 0.046). Both creams were well tolerated with mild application site reactions being the most frequent adverse event. The increased final cure rate in the WR 279,396 group in this small Phase 2 study suggests that the combination product may provide greater clinical benefit than paromomycin monotherapy against L. panamensis cutaneous leishmaniasis.

Figure 1.

Subject disposition. A total of 54 subjects were consented and screened of which 30 were randomized. All but one of the 30 subjects received 20 days application of study drug. One subject missed one day. Subjects who were withdrawn early from the study were withdrawn by the investigator as judged to be treatment failures: one subject in the WR 279,396 group and six subjects in the Paromomycin Alone group.

Figure 2.

Example of response to treatment with WR 279,396. The subject presented with a deep ulcerous lesion surrounded by a large area of induration on the foot. At 1 week after completing treatment (Day 28), the induration had resolved and the ulcer was nearly completely cured. The ulcer completely cured by Day 42 and remained cured for the duration of follow-up.

Figure 3.

Mean percentage cure rate over time for the index lesion. Index lesions start to completely re-epithelialize at Day 28 and continue to heal until about Day 100 after which time, if subjects had a lesion that did not cure; the subject was taken off study and offered other treatment. At Day 49 the curves for the two treatment groups start to separate with lesions treated with WR 279,396 ultimately reaching a higher final cure rate than that for the Paromomycin Alone group.