Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: an 84-week phase III clinical trial.

Currently available testosterone (T) injections in the United States are administered at 2-3 weekly intervals. Less frequent injections with favorable serum T pharmacokinetics would benefit hypogonadal men. The objective of this study is to assess the pharmacokinetics of long-acting testosterone undecanoate (TU) intramuscular (IM) injection in hypogonadal men. An unblinded, multicenter phase 3 clinical trial was conducted in 31 academic centers and contract research organizations. Males (130) more than 18 years of age with serum total T < 300 ng/dL were enrolled and received 750-mg injections of TU at weeks 0 and 4 and every 10 weeks thereafter for 9 injections over 84 weeks. The main outcome variables were serum total T, free T, dihydrotestosterone (DHT), estradiol (E(2)) levels, and safety parameters. After the first injection, patients maintained average trough T concentrations in the adult male range (300-1000 ng/dL or 10.4-34.7 nmol/L) before each injection and at multiple time points measured after the third and fourth injections. Serum free T, DHT, and E(2) levels and their ratios to serum T remained relatively consistent once steady state was attained. TU injections were generally well tolerated, with safety profiles similar to other T replacement. We conclude that hypogonadal patients treated for 84 weeks with a 750-mg IM injection of TU every 10 weeks demonstrated average concentrations of T, its metabolites (DHT and E(2)), and ratios--DHT:T and E(2):T--within the adult male reference range at all time points measured. TU injections would be an acceptable alternative to the currently available 2-3 weekly injectables.