Introduction: A new, first-in-class oral testosterone (T) replacement therapy product [T-undecanoate (TU) capsules] was recently approved by FDA to treat appropriate hypogonadal men. Two clinical trials were conducted to evaluate, in part, the impact of oral TU therapy on important secondary efficacy endpoints: a) Psycho-sexual and/or general health/well-being (Trial I and II) and; b) Body composition (Trial II).
Methods: Hypogonadal men (AM serum T = 300 ng/dL) age 18 to 65 (Trial I) or 75 years old (Trial II) were randomized into open-label, active-comparator (T-gel/solution) trials. Subjects received: Trial 1: Either oral TU (n=166) or a topical T solution (Axiron®; n=55) for 4-6 mos.; or Trial II: Oral TU (n=162) or T-gel (AndroGel® 1%; n=163) for 12 mos. The starting oral TU dose (with food) was 237 mg TU, BID in Trial I and 316 mg TU, BID in Trial II; up to 2 dose-titration opportunities were available to achieve eugonadal T concentrations (Cavg; assayed by LC-MS/MS). In Trial I, Psycho-sexual Daily Questionnaires (PDQ) were completed by study subjects for 7 days at baseline and prior to final clinic visit (Day 105-180). In Trial II, the SF-36 well-being questionnaire was completed on Days 0, 30, 90, 180, 270 and 365 and PDQs were completed for 7 days prior to clinic visits on these same days. Body composition was assessed by DEXA scan on Days 0, 180 and 365. Safety was monitored by physical exam and standard clinical laboratory tests.
Results: Serum T Cavg in response to oral TU was 489 ± 155 ng/dL (mean ± SD) (Trial I) and 628 ± 342 ng/dL (Trial II); 84% of subjects in each trial achieved T Cavg in the eugonadal range. Mean changes from baseline for SF-36 well-being parameters increased significantly in both oral TU and topical T groups. Psycho-sexual questionnaire results also demonstrated statistically significant improvement (p<0.0001) in each parameter at Day 30 and all time points thereafter. At Day 365, oral TU was associated with a statistically significant reduction in fat mass [-2.4 ± 3.6 (SD) kg] and increase in lean mass (+3.2 ± 2.7 kg). Oral TU also significantly increased mean BMD over baseline in hip [+0.01 ± 0.04 (SD) g/cm2] and spine (+0.01 ± 0.02 g/ cm2]. Oral TU exhibited a safety profile consistent with other available T-replacement products -- including the potential to increase blood pressure in some men.
Conclusions: Treatment of hypogonadal men with oral TU yielded circulating T Cavg concentrations in the mid-eugonadal range and significantly improved psycho-sexual, general well-being and body composition parameters. Source of