Abstract
Introduction and Objective: A new, first-in-class oral testosterone (T) replacement therapy product [T-undecanoate (TU) capsules] was recently approved by FDA to treat hypogonadal men. Clinical trials were conducted to evaluate, in part, the impact of oral TU therapy on important secondary efficacy endpoints: Psychosexual and/or general well-being (Trial I and II); and body composition and bone mineral density (BMD) (Trial II).
Subject and 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: Oral TU (n=166) or a topical T solution (n=55) for 4-6 mos.; or Trial II: Oral TU (n=162) or T-gel (n=163) for 12 mos. The starting oral TU dose (with food) was 237 mg, BID in Trial I and 316 mg, BID in Trial II; up to 2 dose-titration opportunities were available to achieve eugonadal T concentrations (assayed by LC-MS/MS). In Trial I, Psychosexual 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. In Trial II body composition and BMD was assessed by DEXA scan on Days 0, 180 and 365. Safety was monitored by physical exam and standard clinical lab tests.
Results: Mean serum T 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 mean T concentrations in the eugonadal range. Statistically significant mean changes from baseline (p<0.0001) for most SF-36 well-being parameters were observed in both oral TU and T-gel groups. Psychosexual questionnaire results also demonstrated statistically significant improvement over baseline (p<0.0001) in most parameters at Day 30 and all timepoints thereafter in both trials. On Days 180 and 365 (v. baseline) oral TU was associated with a significant reduction in fat mass [-1.92 ± 2.79 (SD) and -2.4 ± 3.6 kg, respectively] (p<0.0001) and an increase in lean body mass [+2.87 ± 2.73 and +3.15 ± 2.69 kg, respectively] (p<0.0001). Oral TU increased mean BMD over baseline on Days 180 and 365 in spine [+0.013 ± 0.035 and +0.018 ± 0.042 g/cm2, respectively (p<0.0001)] and hip [+0.006 ± 0.019 and +0.012 ± 0.023 g/cm2, respectively (p<0.0001)]. Oral TU exhibited a safety profile consistent with commonly prescribed topical T-comparators. Modest increases in cuff sBP of 2.8 ± 11.84 (SD) mm Hg and 1.8 ± 10.76 mm Hg were observed in Trial I for both oral TU and the comparator T-solution.
Conclusions: Treatment of hypogonadal men with oral TU yielded circulating mean T concentrations in the mid-eugonadal range and significantly improved psychosexual, general well-being, body composition and BMD parameters comparable to transdermal T administration.
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