Mp59-01 Peyronie's Disease Plaque Transcriptome-wide Analysis Using Rna Sequencing Reveals Targetable Signalling Pathways for Medical Treatment
Year: 2019
Type: article
Abstract: OBJECTIVES: 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with T deficiency to self-administer testosterone enanthate as a single subcutaneous injection once weekly.In a draft guidance document, the FDA recommends characterization of the effect of a drug on blood pressure (BP) during drug development using ambulatory blood pressure monitoring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 26wk 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: The Journal of Urology
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2941595555