(394) Effects of Age, Body Mass Index (BMI) and Diabetic Status on Testosterone Levels, Testosterone Dosing and Safety in Hypogonadal Men Treated with an Oral Testosterone Undecanoate (JATENZO)

Abstract

Abstract Introduction A novel oral testosterone replacement therapy (TRT), testosterone undecanoate (TU, JATENZO) has been shown in 1- and 2-year studies to have durable efficacy and safety. Hypogonadal men are heterogeneous with respect to age, body mass index (BMI), and diabetic status. These factors have been shown to affect the hypothalamic-pituitary-gonadal axis. Objective The purpose of this study is to investigate the role of baseline age, BMI, and diabetic status on change in T levels, final TU dose, and safety. Methods Hypogonadal men, ages 18 – 65 y/o, were recruited into a randomized, open-label, multicenter, dose-titration trial. 222 subjects were randomized to BID TU (n = 166) or testosterone gel (n = 56). Subjects had dose adjustments based on plasma T levels (Cavg). Safety was assessed by standard clinical measures. Post hoc safety, efficacy, and dosing analyses were conducted on subjects who were stratified by age, BMI, and diabetes status. The age groups were <= 44 y/o, 45 – 54 y/o, and => 55 y/o; the BMI groups were < 30 kg/m^2, 30 – 35 kg/m^2, and > 35 kg/m^2; and the subjects were grouped as non-diabetic, pre-diabetic, or diabetic. Results Overall, serum total T Cavg for the oral TU group was 489 ± 12.6 ng/dL (mean ± SE). For all groups, the mean total T was in the eugonadal range. Age, BMI, or diabetes status did not affect key efficacy variables, such as total T or calculated free T, nor key safety variables, such as hematocrit, PSA, liver transaminases, systolic BP, diastolic BP, HDL-C, or LDL-C. There were no differences in the final TU dose among the age categories. In contrast, the final TU dose was significantly different among BMI categories (p=0.0003), and the diabetic status (p < 0.0001). The higher BMI groups need a significantly higher oral TU dose. Those in the pre-diabetic or diabetic groups needed a significantly higher dose than the non-diabetic group. Because the pre-diabetic and diabetic groups had significantly higher BMI, it is difficult to determine if it was diabetes status or BMI that influenced the final dose [baseline BMI: non-diabetic 30.5 ± 0.52 (mean ± SEM), pre-diabetic 32.7 ± 0.54 (p = 0.003 vs the non-diabetic group), diabetic 32.5 ± 0.56 (p = 0.0175 vs the non-diabetic group)]. BMI had a greater effect on the final dose in the non-diabetic group, and its effect appeared to decrease in the pre-diabetic and diabetic groups. See figure for the final mean doses. Although the final total T values were in the eugonadal range, there was also a significantly smaller change from baseline in total T comparing non-diabetics to diabetics (p=0.0042). Conclusions Regardless of age, BMI, or diabetes status, eugonadal total T levels were achieved in men administered oral TU. Age did not influence the final dose. In contrast, BMI and diabetes status influenced the final dose. Patient characteristics (BMI and diabetic status) may guide dosing of testosterone replacement with oral testosterone undecanoate to optimize T levels. Disclosure Yes, this is sponsored by industry/sponsor: Clarus Therapeutics Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Clarus Therapeutics.