Repros Therapeutics reports top line results of Androxal from first of two pivotal studies

In this study, ZA-305, Androxal exhibited superiority in several assessments, particularly the two co-primary endpoints: percent change from baseline in average sperm concentration and percent of subjects considered to be responders.

A responder is defined as an individual achieving a 24 hour average testosterone in the normal range with associated average sperm concentration >= 10 million/mL.

Multiple secondary endpoints also showed statistically significant differences between the Androxal and T gel groups.

These include: change in the important pituitary signaling hormones LH and FSH; percent of subjects that become severely oligospermic (< 10 million sperm/mL); induction of hormone dependence via assessment of morning testosterone levels comparing baseline to one week after the end of dosing; and impact on testicular size at the end of the dosing period.

ZA-305 was designed to enroll 120 men, 40 each into three parallel arms: Androxal(R), approved topical gel and placebo. All three arms were blinded and "double dummied," meaning men received both an active dose and a placebo mimicking the other active. Men on placebo received two placebos, one for each active. The study was of 17 week duration, 16 weeks dosing and 1 week follow-up.

Men (<= 60 years of age) enrolled in the study exhibited sperm counts in the normal range at baseline (> 15 million/mL) on two separate days separated by at least two days. Men also exhibited morning testosterones of < 300 ng/dL on both of those days to be eligible to enter the study.

The number of subjects enrolled into the study was 127, of which 117 completed. Of the enrolled subjects, 44, 42 and 41 subjects were randomized to Androxal(R), a Topical T, and Placebo, respectively. The mean age of the subjects was 47, 45 and 48 years for the Androxal(R), Topical T, and Placebo subjects, respectively. Baseline BMI was similar for the three groups, 33.8, 33.1 and 33.5 for the Androxal(R), Topical T, and Placebo subjects, respectively.

The first primary efficacy endpoint was the percent change from baseline in sperm concentration. The percent change from baseline was found to be unchanged from baseline for Androxal(R)-treated subjects and those treated with Topical T experienced a median 33% decrease from their baseline concentration. This difference was found to be statistically different from baseline (p = 0.0007) as well as statistically different from the Androxal(R) results (p = 0.0004). Table 1 provides additional information on sperm concentration.