Androxal enclomiphene: Phase III amended

Repros amended the identical, double-blind, placebo-controlled, U.S. Phase III ZA-304 and ZA-305 trials to include co-primary endpoints that compare semen concentration outcome for 12.5 or 25 mg oral Androxal for 16 weeks vs. AndroGel 1.62% testosterone gel. The new co-primary endpoints are proportion of patients with sperm concentrations <10 million/mL and percentage change from baseline in semen concentration at 16 weeks. The studies previously had a composite endpoint of normal 24-hour average testosterone levels of 300-1,040 ng/dL and sperm concentration of >=15 million/mL. The company said the 2 trials are >80% powered to meet the 2 new co-primary endpoints.

Repros said it made the amendments after discussions with FDA, which stated that a sperm concentration of 10 million/mL is recognized as the threshold for needing in vitro fertilization and might be a more clinically relevant cutoff for defining low sperm count than 15 million/mL. Repros said that while FDA recommended resubmitting the revised protocols before starting the trials, at the time the company had already "substantially" enrolled the trials. ...