Repros Therapeutics reported it has received Institutional Review Board (IRB) approval to commence a Phase 2b study of Androxal (enclomiphene) in men with secondary hypogonadism. The study will enroll up to 120 men with morning testosterone levels <250 ng/dl at 20 sites across the U.S. The men must be naïve to testosterone therapy or have not used testosterone for at least 6 months. The men will be equally randomized to four different groups, double blind Androxal 12.5 mg and 25 mg, matching placebo and open label Testim used per manufacturer’s recommendations. Men will be dosed for 3 months. The primary efficacy endpoint of the study is change in morning testosterone levels comparing the baseline visit to the levels achieved after three months to those achieved for placebo. Changes in pituitary hormones that control testicular function will be assessed as secondary efficacy measures.
Androxal is an orally active small molecule under development that restores normal pituitary response in men resulting in normalization of testosterone and luteinizing hormone (LH) levels.
On February 8, 2010, the company announced that it had submitted to the US FDA the final clinical study report from its trial assessing the impact of administration of a topical testosterone gel and Androxal on spermatogenesis. The study report from this small trial suggested a deleterious effect on spermatogenesis in men using exogenous testosterone treatments that result in circulating levels of the hormone that are within the normal range. Levels of suppressed fertility for men on testosterone in the study were consistent with that which has been reported in the literature for testosterone treatments in general. In the study, oligospermia (<20 million sperm per milliliter) was noted in the majority of the testosterone treated subjects with some exhibiting azoospermia (no detectable sperm). By contrast a majority of men randomized from the same population to Androxal saw an improvement in their sperm counts and they were all well above the normal criteria of sperm concentrations considered to be indicative of fertility. The difference between the Androxal and the testosterone group was statistically significant (p<0.01).
Presently, the company is awaiting the FDA’s response to the above noted submissions. The submission also includes a refined rigorous indication statement defining Androxal’s intended patient population. In the hope that the Agency agrees with the indication statement, the Company has begun drafting phase-III protocols that it believes will clearly demonstrate to the US FDA the negative impact of exogenous testosterone on fertility as evidenced by an adverse effect on spermatogenesis. Within those same studies the Company believes it will again show that Androxal restores the “whole man” by both improving testosterone levels into the normal range and improving or maintaining sperm counts via the drug’s action, restoration of the hypothalamic-pituitary- testes axis which results in normal testicular function. There can be no assurance that the US FDA will concur with the company’s belief that it is ready to embark on phase-III studies.The company announced that it has completed the enrollment process for the one-year study, DEXA (ZA-303), evaluating the effects of Androxal on bone mineral density. The company completed the enrollment three months before the scheduled date. The company expects to file a New Drug Application (:NDA) for Androxal primarily on the basis of data from the DEXA study by mid-2014.