Study ZA-302 (Pivotal Efficacy Study)
For study ZA-302, results were almost identical to the previously reported study ZA-301. Both co-primary endpoints were met in each of the Androxal pivotal efficacy studies with respect to T normalization and sperm function conducted under a Special Protocol Assessment (SPA). Under an SPA, efficacy endpoints are predetermined with the FDA and if the endpoints are met the efficacy component of the drug dossier is deemed successfully completed.
Study ZA-302 was increased in size to account for subjects referred from an infertility clinic to determine whether or not that site affected efficacy outcomes. In study ZA-302, all efficacy outcomes were met with or without the aforementioned site and were very similar to the outcomes reported for study ZA-301.
As was observed in study ZA-301, the FDA prescribed threshold for efficacy of inducing 75% or more men to testosterone within the normal range was also met. 79% of Androxal-treated men met the criteria in study ZA-301 and 81% met that threshold in study ZA-302. The outcome was met with or without the aforementioned site. As with the previous study, there were no 24 hour average testosterone levels outside of the normal range. Excursions above 1,500 ng/dL have raised significant concerns with the FDA in the past for exogenous T replacements.The trial was to meet a non-inferiority delta comparing drug to placebo for drops of sperm concentrations greater than or equal to 50% comparing an average of two baseline assessments compared to two assessments after 12 weeks of treatment of 20%. The Company believes that the endpoint has been met and confirmed in the second study. Study ZA-301 recorded a lower confidence bound of -0.194 (final ITT, 1 of 38 placebo, 16 of 113 drug) and study ZA-302 had a lower confidence bound of -0.183 and -0.196 with or without the aforementioned site (preliminary ITT 2 of 47 placebo, 20 of 134 drug with aforementioned site, 2 of 40 placebo and 18 of 113 drug without site). There were no observed anomalies in study conduct in the second study.