Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism.

Abstract

Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations. The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie). In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225mg oral testosterone undecanoate twice daily, and doses were adjusted by 75mg/dose at weeks 4 and 8 based on average serum total testosterone concentration and maximum observed serum concentration. The primary endpoint was the proportion of patients receiving oral testosterone undecanoate with serum total testosterone concentration within the eugonadal reference range (300-1140ng/dL). Secondary endpoints included the proportion of patients with maximum serum total testosterone concentrations within predetermined limits, safety parameters, and quality-of-life endpoints including the Short Form-36v2 Health Survey, Psychosexual Daily Questionnaire, and International Prostate Symptom Score. Overall mean±SD baseline testosterone was 205.7±71.6ng/dL. For patients receiving oral testosterone undecanoate, 87.4% demonstrated a 24-h average serum total testosterone concentration within the reference range following titration. Oral testosterone undecanoate demonstrated a nominal statistically significantly greater mean change from baseline than 1.62% topical testosterone gel for Short Form-36v2 Health Survey measures of mental health (2.91vs. -0.10; p=0.035), and mental component summary (3.82vs. 0.55; p=0.009); and Psychosexual Daily Questionnaire measure of weekly negative mood (-0.57vs. -0.20; p=0.021). Safety endpoints were comparable between therapies. No deaths or treatment-related serious adverse events were reported. Male patients with hypogonadism receiving oral testosterone undecanoate 225mg twice daily demonstrated improvements in libido and sexual frequency. Serum testosterone concentrations were within the reference range in 87% of patients without dose titration.