2.3. Outcomes and Assessments
redness, itching, swelling, prostate, pain/tenderness, MP
ADVERSE EVENTS, SECONDARY, PROSTATE, INDURATION
The primary objective of all the trials was to assess the duration of action of an initial loading dose regimen of teverelix DP in terms of suppression of testosterone to below the castration level (0.5 ng/mL). The secondary objectives were: to assess the pharmacodynamics of teverelix DP in terms of its ability to suppress and maintain plasma testosterone levels below the castration level after 3 weeks of treatment (<0.5 ng/mL until 2 consecutive, increasing testosterone levels above the castration level with the latter recording above 2 ng/mL); to assess the effects on LH and prostate-specific antigen (PSA); and to assess the safety of teverelix DP. The safety evaluation included adverse events (AEs), clinical laboratory tests, vital signs, physical examinations. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA v7.0, Herndon, VA, USA). In addition, a formal injection site inspection was performed in 3 trials (ARD-0301-003, ARD-0301-008 and ARD-0301-010) to assess local tolerability, i.e., redness, swelling and induration (size/diameter, nature and firmness), itching and pain/tenderness. A transrectal ultrasound (TRUS) to assess total prostatic volume and the volume of peripheral and transitional zones of the prostate was conducted in the same three trials.Serum total testosterone and luteinizing hormone (LH) were measured using validated assays at MDS Pharma Services, Grossmoorbogen 25, 21,079 Hamburg, Germany. Total testosterone and LH was measured by double-antibody RIA kits from MP Biochemicals (formerly ICN Biochemicals, Santa Ana, CA, USA) after extraction of the serum with hexane and ethyl acetate using a gamma-counter Berthold 2104 with its own evaluation software. The assay kits were already validated by the producer for the standard use in human serum or plasma. Re-validation of the testosterone assay was completed by MDS Pharma Services (King of Prussia, PA, USA). The lower limit of quantification (LLoQ) for testosterone was reported as 0.0259 ng/mL. For LH, the LLoQ was 0.3 IU/L. All analyses and reporting were completed in accordance with Good Laboratory Practice (GLP).Teverelix levels were analyzed in plasma samples by HFL Ltd., Fordham, UK or by Professor Huy Ong’s laboratory at the University of Montreal, Montreal, QC, Canada. PSA measurements were performed at local laboratories. The assessment days are shown in 