Oral formulation of testosterone displays safety at 2 years

A novel oral formulation of testosterone undecanoate (TU; trade name: Jatenzo) displayed a safety profile that is consistent with other approved testosterone products, according to a recent study.1

Investigators reporting their findings at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting noted that no evidence of liver toxicity was observed with the treatment at 2 years.

For the study, the investigators conducted 2 open-label, multicenter, dose titration trials in men with hypogonadism (defined as serum testosterone of ≤ 300 ng/dL) aged 18 to 75 years. Trial 1 was a randomized, active-controlled, 2-arm, 12-month study, and Trial 2 was a long-term extension of those patients 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,” noted the authors.

Physical exam, adverse event reporting, and routine clinical laboratory measurements were used to evaluate safety.

A total of 86 patients participated in both trials. Testosterone concentration increased from 193.75 ± 9.44 ng/dL (mean ± SEM) at baseline to 475.5 ± 49.7 ng/dL after 24 months of therapy with oral TU. In addition, 84% of men achieved testosterone in the eugonadal range (300 ng/dL to 1000 ng/dL) after 90 days of therapy.

The investigators reported that mean testosterone concentrations remained in the eugonadal range throughout Trial 2. In addition, there were no clinically significant changes in liver function tests throughout the 2 trials. At day 270, 1 patient had an ALT level of 227 U/L, which was more than 4 times the ULN. The patient’s ALT was measured again at day 290 after continued TU use, and the level had dropped to 87 U/L, or less than 2 times the ULN.

A modest initial increase in prostate-related growth end points (ie, prostate-specific antigen and prostate volume) was reported that stabilized over time. There were no significant changes in International Prostate Symptom Score total score observed.

“There were significant, yet modest, increases in mean HCT (44.3 ± 0.3 to 46.6 ± 0.5%, P < .001) and cuff systolic BP (127.1 ± 1.2 to 131.8 ± 1.67 mmHg vs BL, P = .006),” the authors wrote. Cardiovascular end points such as HDL-C, hematocrit, and blood pressure changed initially and then stabilized throughout the trials.

“The long-term efficacy and safety profile of oral TU may provide a treatment option that avoids issues associated with other [testosterone replacement therapies], such as injection site pain or transference to partners and children,” the authors concluded.

Reference

1. Swerdloff R, Honig S, Wang C, et al. Two-year administration data of an oral testosterone undecanoate (TU) formulation in hypogonadal men. Real-world experience with first FDA-approved oral testosterone undecanoate formulation. Paper presented at 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021; Scottsdale, Arizona. Abstract 003.