Presentation Authors: Jed Kaminetsky, New York , NY, Marc Gittelman, Aventura, FL, Mohit Khera*, Houston, TX, Martin Miner, Providence, RI, Alexander Pastuszak, Houston, TX, James Tursi, Jonathan Jaffe, Ewing, NJ
Introduction: The Subcutaneous Testosterone Enanthate Auto-Injector (SCTE-AI) has been designed to safely deliver testosterone (T) by allowing patients with T deficiency to self-administer testosterone enanthate as a single subcutaneous injection once weekly. In a draft guidance document, the FDA recommends characterization of the effect of a drug on blood pressure (BP) during drug development using ambulatory blood pressure monitoring (ABPM). During a rigorous safety study of SCTE-AI, 24-hr APBM data were collected.
Methods: Study QST-15-005 was designed to assess the 26-wk safety of SCTE-AI in T-deficient men. The study enrolled 150 men at 19 US sites who initially received a weekly dose of 75 mg. At Week 6, a pre-dose trough T (TT) level was obtained and dosing adjusted to maintain TT levels of 300-650 ng/dL through Week 26. ABPM for 24 hours was performed at baseline (BL), Week 6, and Week 12 and analyzed for changes from BL.
Results: At Week 12, 24hr-ABPM showed mean systolic BP (SBP) increased 3.7 mmHg and diastolic BP (DBP) increased 1.3 mmHg from BL. TT level and change in BP were not correlated. Change in BP had a negative correlation with BL BP. Patients with ABPM-defined hypertension (>130/80 mmHg) had smaller increases in SBP than normotensives (0.3 vs 7.2 mmHg). Week 12 SBP increases were similar whether or not patients were taking antihypertensive drugs. In-clinic BP rose initially and remained stable throughout the study. Week 26 mean in-clinic SBP and DBP increased from 125.6 and 78.2 mmHg at BL to 129.0 and 80.0 mmHg, respectively. In total, 34 (25.6%) men had adverse drug reactions (ADRs), mostly mild or moderate. The most frequent ADRs were increased hematocrit (7.5%), injection site hemorrhage (4.5%), injection site bruising (3.0%), and increased prostate-specific antigen (3.0%). There were three treatment-emergent adverse events for hypertension.
Conclusions: SCTE-AI was tested in a Phase 3 study that included a rigorous ABPM component. The product was well-tolerated. Overall, mild increases in BP were noted and inversely correlated with BL BP. The long-term clinical effects of these drug-related increases in BP are unknown, and the study was not powered to determine the effect of these changes on major adverse cardiovascular events. BP should be periodically monitored at follow-up visits in patients receiving SCTE-AI and managed appropriately with consideration of the potential risk of major adverse cardiovascular events in those men repleted with T therapy.
Source of Funding: Antares Pharma Inc.