First Long Acting Testosterone Undecanoate Injection to Treat Male Hypogonadism:
21 Month Safety and Efficacy Outcomes
Abraham Morgentaler, MD1, Joel M. Kaufman, MD2, Ridwan Shabsigh, MD3, Martin M. Miner, MD4, Ronald S. Swerdloff, MD5, Christina Wang, MD5, Adrian S. Dobs, MD, MHS6.
1Harvard Medical School, Boston, MA, USA, 2University of Colorado School of Medicine, Denver, CO, USA, 3Maimonides Medical Center and Columbia University, New York, NY, USA, 4The Warren Alpert Medical School of Brown University, Providence, RI, USA, 5David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 6Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Pharmacokinetic data from a phase 3 study regarding testosterone undecanoate (TU) 750 mg injections for treatment of hypogonadism was previously reported for time points up to 24 wks. The purpose of this study was to report new, longer-term data with results up to 21 mo of treatment.
This was a multicenter, US based study of TU 750 mg injections given at baseline, at wk 4, and every 10 wks thereafter through 84 wks of treatment. Males ≥18 yrs of age with primary or secondary hypogonadism and a screening serum T concentration <300 ng/dL were eligible. Frequent blood sampling was collected during wks 14-24 (after 3rd injection) and wks 24-34 (after 4th injection). Trough T samples were collected at each injection visit. Extensive safety monitoring procedures included clinical laboratories, comprehensive prostate health, and adverse event (AE) assessments.
130 patients were enrolled, with >75% completing all injections during the treatment period. Patients average 54 yrs of age. Average 10 wk T concentrations during wks 14-24 were 494.6 ng/dL (SD 141.46 ng/dL). T concentration profiles were similar for each injection interval (Figure 1), with peaks and nadirs nearly identical from one injection to the next, indicating consistent T replacement for these intervals. Average trough T concentrations were within normal range (300 to 1000 ng/dL) throughout the entire 21 mo treatment period.
Injections were well tolerated. AEs reported were minor and non-serious; 36.7% of patients experienced at least one possibly treatment related AE during the study, with acne and increased prostate specific antigen (PSA) the most commonly reported events, reported in 6.2% and 5.4% patients, respectively. There were 7 (5.4%) patients with increased PSA, 3 (2.3%) patients with increased hematocrit and/or hemoglobin, and 2 (1.5%) patients diagnosed with prostate cancer during the 21 mo study period.
This study demonstrates that TU 750 mg every 10 wks for 21 mo effectively provides consistent T concentrations within the normal range, a favorable safety profile and high level of patient tolerability.
Figure 1: Mean (SD) serum total T concentrations after 3rd injection (wks 14-24) and 4th injection (wks 24-34) of TU 750 mg at steady state. (Horizontal lines are reference ranges for serum total T.)