A New Oral Testosterone Undecanoate Formulation Restores Testosterone to Normal Concentrations in Hypogonadal M

Context: A novel formulation of oral testosterone (T) undecanoate (TU) was evaluated in a phase 3 clinical trial. Objective: Determine efficacy, short-term safety, and alignment of new oral TU formulation with current US approval standards for T replacement therapy. Design: Randomized, active-controlled, open-label study. Setting and Patients: Academic and private clinical practice sites; enrolled patients were clinically hypogonadal men 18 to 65 years old. Methods: Patients were randomized 3:1 to oral TU, as prescribed (JATENZO (R) ; n = 166) or a topical T product once daily (Axiroe (R); n = 56) for 3 to 4 months. Dose titration was based on average T levels (C-avg) calculated from serial pharmacokinetic (PK) samples. T was assayed by liquid chromatographymass spectrometry/mass spectrometry. Patients had 2 dose adjustment opportunities prior to final PK visit. Safety was assessed by standard clinical measures, including ambulatory blood pressure (BP). Results: 87% of patients in both groups achieved mean T C-avg in the eugonadal range. Sodium fluoride-ethylenediamine tetra-acetate plasma T C-avg (mean +/- standard deviation) for the oral TU group was 403 +/- 128 ng/dL (-14 +/- 4 nmol/L); serum T equivalent, -489 +/- 155 ng/dL (17 +/- 5 nmol/L); and topical T, 391 +/- 140 ng/dL (similar to 14 +/- 5 nmol/L). Modeling/simulation of T PK data demonstrated that dose titration based on a single blood sample 4 to 6 h after oral TU dose yielded efficacy (93%) equivalent to C-avg-based titration (87%). Safety profiles were similar in both groups, but oral TU was associated with a mean increase in systolic BP of 3 to 5 mm Hg. Conclusion: A new oral TU formulation effectively restored T to mid-eugonadal levels in hypogonadal patients.