Novel Oral Testosterone Formulation Improves Male Well Being Without Compromising International Prostate Symptom Scores

Abstract

Introduction: Male hypogonadism results from insufficient secretion of testosterone (T) and is characterized by low serum T concentrations. Common symptoms of hypogonadism include decreased libido, impotence, weakness, low energy, depression and/or loss of motivation, memory and concentrating issues, and sleep disturbances. Several forms of T replacement are available. Testosterone undecanoate (TU) is a testosterone prodrug available in oral formulations. A novel TU formulation, SOV2012-F1, has been submitted for FDA consideration under the name KYZATREX®. While TU efficacy is measured by serum total T, patientfocused endpoints such as Patient Reported Outcomes (PROs) are valuable indicators of well-being and psychosexual symptom abatement. Methods: A Phase 3, randomized, multicenter, open-label, active-controlled trial, comparing SOV2012F1 (testosterone undecanoate capsules) (n=214) with AndroGel® (1.62% topical testosterone gel) (n=100) enrolled males aged 18 to 65 years with hypogonadism (serum total T levels ≤281 ng/dL). A key exploratory endpoint was change from Baseline (ΔBL) after 52 weeks of treatment in the following PROs: International Prostate Symptom Score (IPSS), Psychosexual Daily Questionnaire (PDQ), Short Form Health Survey 36 item (SF-36), and the International Index of Erectile Function (IIEF). Results: Total or overall scores for all PROs (IPSS, PDQ, SF-36 and IIEF) showed increased improvement in the SOV2012-F1 group relative to the Androgel group, and all but IPSS demonstrated improvement relative to BL. For IPSS, due to the potential that T could worsen urinary symptoms, the ΔBL would ideally be small to reflect minimal impact. Change for the SOV2012-F1 and AndroGel groups was, respectively, 0.6 and 1.0. Further, the IPSS total score was not significantly different from BL in the patients receiving SOV20212-F1 (p = 0.5659). For PDQ, a clinically meaningful improvement of sexual desire in hypogonadal men age ≥65 years is ≥0.7; mean ΔBL was 1.6 in the SOV2012-F1 group versus 1.4 in the AndroGel group. In the SF-36, the mean ΔBL total score was 83.7 in the SOV2012-F1 group and 70.2 in the AndroGel group. Further, post hoc analysis of the Health Change category found a significant (p ≤ 0.05) improvement in patient perspectives on health over the course of the study. The overall satisfaction score of the IIEF trended towards significance for the SOV2012-F1 group with a mean ΔBL score of 2.3 versus and 1.6 in the AndroGel group. The ΔBL for the 4 domains of male sexual function were small and consistent between the SOV2012-F1 and AndroGel groups. Comparable results were noted for Early Withdrawals and All Subjects across all PROs. Conclusion: Treatment with SOV2012-F1 for 52 weeks exceeded AndroGel patient satisfaction as measured by PROs including IPSS, PDQ, SF-36 and IIEF, demonstrating clinical distinction. Further analysis of SOV2012-F1 will be forthcoming.