(393) Pooled Safety Analysis of Ten Clinical Studies Evaluating Fixed-Dose Oral Testosterone Undecanoate in Male Patients With Testosterone Deficiency

Abstract

Abstract Introduction Oral testosterone undecanoate (TU) was approved outside the United States 50 years ago and is currently used in several countries for the treatment of men with testosterone deficiency. The efficacy of prior oral TU is limited by a short half-life, requiring frequent dosing and administration with meals. A novel formulation of fixed-dose TU is now indicated for the treatment of testosterone deficiency (FDA approved March 2022). In a phase 3 study (NCT03242590: 1021-16-002) evaluating the efficacy and safety of fixed-dose oral TU 225 mg twice daily in adult men with testosterone deficiency, oral TU was well tolerated and restored testosterone levels to eugonadal ranges in most patients. Objective The objective of this pooled analysis of ten clinical studies (LPCN 1021-09-001, S361.1.001, M12-778, M13-298, 1021-14-001, LPCN 1021-16-002, LPCN 1021-16-003, LPCN 1021-13-001, LPCN 1021-18-001, LPCN 1021-18-003) was to further evaluate the safety of fixed-dose TU administered to adult men with testosterone deficiency. Methods This pooled analysis included men with testosterone deficiency who were enrolled or randomized in one of ten clinical studies and received at least one dose of study drug, which included fixed-dose TU, dose-adjusted TU, or topical testosterone gel. Data from separate studies were allocated to defined treatment groups, and these data were pooled to present a safety summary of patients treated with fixed-dose TU. Treatment groups were defined as follows: all fixed-dose TU patients, active control patients (dose-adjusted TU or topical testosterone gel), and placebo patients. Participants in a crossover study of various fixed-dose TU doses were counted once overall for analysis, and data relating to the highest dose were used. Results Overall, 777 patients were included in this pooled analysis: 654 received fixed-dose TU, 104 received topical testosterone gel, 34 received dose-adjusted TU, and 18 received placebo. Baseline characteristics are available on Table 1. Among 654 patients who received fixed-dose TU, 549 (83.9%) patients completed their respective study, and 15 (2.3%) patients discontinued because of an AE. The most frequently occurring treatment-emergent related adverse events (AEs) for patients treated with fixed-dose TU included headache (10 [1.5]), hematocrit increase (8 [1.2]), and acne (6 [0.9]) (Table 2). Three (0.5%) patients receiving fixed-dose TU experienced a blood pressure increase and 13 (2.0%) exhibited hypertension. No patients receiving fixed-dose TU experienced an increase in hepatic enzymes. The mean change from baseline (SD) in hematocrit (HCT) for patients receiving fixed-dose TU was 0.003% (0.029); three patients receiving fixed-dose TU discontinued because of HCT >54%. No patients in this pooled analysis experienced a serious AE (SAE) related to study treatment, and no deaths occurred. Conclusions In this pooled analysis of ten clinical studies in male patients with testosterone deficiency, fixed-dose TU was well tolerated with no hepatic adverse events, no drug-related SAEs, and no deaths. Disclosure Yes, this is sponsored by industry/sponsor: Halozyme (previously Antares) Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Halozyme (previously Antares)