Osanetant to Reduce Testosterone Levels in Men with Prostate Cancer, PORT-MAP Trial

Inclusion Criteria

• Ability of participant OR legally authorized representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Males >= 18 years
• Histologic diagnosis of adenocarcinoma of the prostate (PCa)
• Planned radical prostatectomy within the study period
• Testosterone >= 150ng/ml
• Leukocytes >= 1.5 K/UL
• Absolute neutrophil count >= 1.5 K/UL * NOTE: Patients with established diagnosis of benign neutropenia are eligible to participate with absolute neutrophil count (ANC) between 1000-1500 if in the opinion of treating physician the trial treatment does not pose excessive risk of infection to the patient
• Platelets >= 100 K/UL
• Hemoglobin >= 9 g/dL
• Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault equation
• Total bilirubin =< 1.5 x ULN OR direct bilirubin =< 1 x ULN
• Aspartate aminotransferase and alanine aminotransferase =< 2.5 x ULN unless liver metastases are present, in which case they must be =< 5 x ULN
• Men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception for the duration of study participation. Men of child-bearing potential must not father a child or donate sperm while receiving investigational treatment. Following treatment (standard of care prostatectomy) there is no further child-bearing potential

Exclusion Criteria

• Current or recent (within 6 months) use of testosterone/estrogen modulating agents (leuprolide, degarelix, bicalutamide, enzalutamide, apalutamide, darolutamide, abiraterone, systemic ketoconazole, tamoxifen, etc)
• Current use of CYP3A4 inhibitors
• Subjects using the following medications within 2 weeks prior to first dosing (or within 5 times the half-life of that medication, whichever is longer) will be excluded from the study: * Inhibitors of CYP3A4 (including but not limited to macrolide antibiotics, human immunodeficiency [HIV] protease inhibitor, azole antifungal drugs, cyclosporine, calcium channel inhibitor, cimetidine) * Inducers of CYP3A4 (including but not limited to rifampicin, carbamazepine, efavirenz, bosentan, modafinil, St. John's Wort), medications with narrow therapeutic index that are metabolized CYP3A4 and/or CYP2D6 are not allowed from screening until up to 5 half-lives after last dose of osanetant is administered
• Cognitive impairment (defined as the presence of diagnosed dementia)
• Impaired renal function: Creatinine (Cr) > 1.8
• Medical history of osteoporosis
• Current systemic corticosteroid, long-term opioid, spironolactone, or eplerenone use
• Has a known allergic reaction to any excipient contained in the study drug formulation
• Active grade 3 (per the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment
• Active coronavirus disease 2019 (COVID-19) infection
• Any history of underlying liver disorder, including hepatitis (see below)
• Any evidence of acute or chronic hepatitis B or C on screening testing
• Elevation of any or all liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin) above the upper limit of normal (ULN) at baseline testing prior to enrollment
• A family history of hepatitis or currently living with a person who has been given a diagnosis of hepatitis
• A history of or currently working as a sex worker
• A history of or currently using intravenous (IV) drugs
• A self-reported history of alcoholic dependency or abuse
• A history of or current diagnosis of cardiovascular disease including heart failure, coronary artery disease, uncontrolled hypertension, uncontrolled diabetes; arrhythmias (or history of), or clinically relevant electrocardiography (ECG) abnormalities at baseline