Abstracts from the New England Section of the AUA 2021

NE-AUA 2021 Abstracts Scientific Session V: ED/Infertility 48 Safety Analysis of an Oral Testosterone Undecanoate (TU) Formulation Following 2 Years of Administration in Hypogonadal Men Ronald Swerdloff, MD 1 , Ricardo M. Munarriz, MD 2 , Stanton C. Honig, MD 3 , Christina Wang, MD 1 , B. Woun Seo, PhD 4 , Nestor Rohowsky, MA 5 , Robert E. Dudley, PhD 4 1 Lundquist Institute at Harbor-UCLA, Torrance, CA, USA; 2 Boston University School of Medicine, Boston, MA, USA; 3 Yale School of Medicine, New Haven, CT, USA; 4 Clarus Therapeutics, Inc., Northbrook, IL, USA; 5 Integrated Data Consultation Services, Inc., LaGrange, IL, USA 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 USwas methyl-Twhich has been associated with hepatotoxicity. The objective of this study was to evaluate the safety and efficacy of a novel oral T undecanoate (TU) formulationwith 2 year followup. Materials & 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 increase in PSA (0.26 ± 0.28 ng/mL vs. BL @ d730). There were not any 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 prostate-related growth variables and CV endpoints changed initially and stabilized throughout the 2 trials. For example, systolic BP varied 3 - 6 mm Hg from BL throughout the study. Conclusions: 2 year follow up data with this oral TU formulation is an option for hypogonadal men and has a safety profile consistent with other approved T products. Notably, no evidence of liver toxicity was observed. The long-term efficacy and safety profile at 2 years 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. Safety Analysis of an Oral Testosterone Undecanoate (TU) Formulation Following 2 Years of Administration in Hypogonadal Men Ronald Swerdloff, MD 1 , Ricardo M. Munarriz, MD 2 , Stanton C. Honig, MD 3 , Christina Wang, MD 1 , B. Woun Seo, PhD 4 , Nestor Rohowsky, MA 5 , Robert E. Dudley, PhD 4 1 Lundquist Institute at Harbor-UCLA, Torrance, CA, USA; 2 Boston University School of Medicine, Boston, MA, USA; 3 Yale School of Medicine, New Haven, CT, USA; 4 Clarus Therapeutics, Inc., Northbrook, IL, USA; 5 Integrated Data Consultation Services, Inc., LaGrange, IL, USA 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 USwas methyl-Twhich has been associated with hepatotoxicity. The objective of this study was to evaluate the safety and efficacy of a novel oral T undecanoate (TU) formulationwith 2 year followup. Materials & 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 increase in PSA (0.26 ± 0.28 ng/mL vs. BL @ d730). There were not any 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 prostate-related growth variables and CV endpoints changed initially and stabilized throughout the 2 trials. For example, systolic BP varied 3 - 6 mm Hg from BL throughout the study. Conclusions: 2 year follow up data with this oral TU formulation is an option for hypogonadal men and has a safety profile consistent with other approved T products. Notably, no evidence of liver toxicity was observed. The long-term efficacy and safety profile at 2 years 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. 47 25