012 Two-Year Administration Data of an Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men

Autor: R. Swerdloff, S. Honig, C. Wang, M. Gittelman, B.W. Seo, N. Rohowsky, R. Dudley
Rok vydání: 2022
Předmět:
Zdroj: The Journal of Sexual Medicine. 19:S128-S128
ISSN: 1743-6109
1743-6095
DOI: 10.1016/j.jsxm.2022.03.548
Popis: Introduction An oral testosterone (T) replacement therapy (TRT) would be the preferred administration route for many hypogonadal men. Until recently, the only oral TRT approved in the US was methyl-T which has been associated with hepatotoxicity. The safety of a novel oral T undecanoate (TU) formulation was evaluated in hypogonadal men with two-year follow up. Methods Two open-label, multicenter, dose-titration trials were conducted in hypogonadal men (serum T ≤ 300 ng/dL) age 18-75 years. Trial I was a randomized, active-controlled, 2-arm, 12-month study. Trial 2 was a long-term extension of those who completed Trial 1. Statistical analyses were only conducted with the subjects who completed Trial 1 and continued treatment in Trial 2, thus providing up to 2 full years of data. Safety was assessed by physical exam, AE reporting, and routine clinical laboratory measurements. Results Overall, 86 subjects participated in both studies. T concentration increased from 193.75 ± 9.44 ng/dL (Mean ± SEM) at baseline (BL) to 475.5 ± 49.7 ng/dL after 24 Mo of therapy with oral TU, and 84% of men achieved T in eugonadal range (300-1000 ng/dL) after 90 days of therapy. Mean T concentrations remained in the eugonadal range throughout Trial 2. There were no clinically significant changes in liver function tests – ALP (64.05 ± 1.95 to 53.74 U/L ± 1.86 U/L), ALT (27.8 ± 1.40 to 26.7 ± 1.6 U/L), AST (21.6 ± 0.76 to 22.0 ± 1.0 U/L), and bilirubin (0.58 ± 0.03 to 0.52 ± 0.03 mg/dL) throughout the two studies. At d270, one subject had an ALT level of 227 U/L, which was > 4x the ULN (ULN for ALT = 45 U/L). Despite continued use of oral TU, ALT was measured again on d290, and the level dropped to 87 U/L, < 2x ULN. This was the only instance of an LFT elevation. There was a modest initial increase in prostate-related growth endpoints (i.e. PSA and prostate volume) that stabilized over time. Although there was a slight increase in prostate-growth related endpoints, there were no significant changes in IPSS total score (-0.06 ± 3.9 vs BL). There were significant, yet modest, increases in mean HCT (44.3 ± 0.3 to 46.6 ± 0.5%, p < 0.001) and cuff systolic BP (127.1 ± 1.2 to 131.8 ± 1.67 mmHg vs BL, p = 0.006). The change in CV endpoints, including HDL-C, hematocrit, and BP, changed initially and stabilized throughout the 2 trials. For example, systolic BP varied 3 – 6 mm Hg from BL throughout the study. Conclusion This oral TU formulation is an option for hypogonadal men and has a safety profile consistent with other approved T products, such as a rise in hematocrit and a decrease in HDL-C. Notably, no evidence of liver toxicity was observed over 2 years. The long-term efficacy and safety profile of oral TU may provide a treatment option that avoids issues associated with other TRTs, such as injection site pain or transference to partners and children. Disclosure Work supported by industry: yes, by Clarus Therapeutics. A consultant, employee (part time or full time) or shareholder is among the authors (Clarus Therapeutics).
Databáze: OpenAIRE
Externí odkaz: