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

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(®); n = 166) or a topical T product once daily (Axiron(®); 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 chromatography–mass 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 (~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.