Androxal in Male Infertility
This is an exploratory, single center, randomized, parallel, double-blind placebo- and active-controlled trial in adult males ages 18 to 35 years of age who have male infertility of unknown cause. Approximately 50 men will be randomly assigned to one of two treatment groups according to a 1:1 ratio. About half of the men will receive 25mg Androxal and half of the men will receive a placebo (non-active pill) for 16 weeks. This study will last approximately 4 months and involve up to 7 visits.
It has been estimated that 4 to 5 million men in the United States are testosterone deficient, but fewer than 10% currently receive testosterone replacement therapy. There are many reasons for the low number of men receiving testosterone replacement therapy, one of which is the route of administration. The currently approved androgen therapies are oral products, injectables, patches, buccal systems, and gels, and each has disadvantages. Oral preparations may be associated with hepatotoxicity and produce unfavorable effects on serum lipid profiles and carbohydrate metabolism. Injectables are associated with uneven levels of serum testosterone leading to fluctuations in mood, libido, and energy levels. Patches may require intrusive preparation, cause skin irritation or not adhere properly. A testosterone gel has overcome some of the above problems and has gained acceptance, but there are indications that men do not apply the gel correctly.
Previous studies showed that Androxal significantly increases total testosterone levels in men with low values at baseline. Additional studies found not only was Androxal non inferior to a topical gel, it was found to maintain sperm counts in the normal range. Subjects will be randomized into one of the two treatment arms, using a block size of 4. The order in which the treatments are assigned in each block is randomized and this process is repeated for consecutive blocks of subjects until all subjects are randomized. This process ensures that after every fourth randomized subject, the number of subjects in each treatment group is equal.
To allow subjects in screening once the target 50 subjects have been enrolled and to account for dropouts, 75 randomization codes will be generated. As subjects are enrolled in the study, they will be assigned unique consecutive numbers starting at 001. At least 50 subjects who meet all the entry criteria will be randomized 1:1 such that approximately 25 subjects are assigned to the Androxal treatment arm and approximately 25 subjects are assigned to the placebo arm.
Placebo controlled studies are the gold standard of clinical trials and should be attempted whenever the indication and current medical practice will allow. This study is investigating a product to increase sperm concentration in subjects with idiopathic male infertility and secondary hypogonadism, low testosterone. Subjects with idiopathic male infertility do not require treatment to be healthy and approximately 18 weeks on a placebo is unlikely to harm the subjects in any way. Standard of care for idiopathic male infertility today allows subjects and physicians the option to not medically treat the disease. Therefore, the use of a placebo control in this study is well justified and will provide the best mechanism to assess treatment effect.
