Teverelix is a potential treatment option for the prevention of acute urinary retention recurrence in men suffering from benign prostatic hyperplasia.

Purpose: To evaluate the efficacy and safety of teverelix in treatment naïve patients aged over 50 years with symptomatic benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS), and to explore teverelix' potential in preventing AUR secondary to BPH with the aim to inform a planned Phase 2 trial.

Methods: This Phase 2, multicenter, randomized, double-blind, placebo-controlled study involved BPH patients with an International Prostate Symptom Score (IPSS) ≥ 13 and uroflow < 13 mL/sec. After a 4-week single-blind placebo run-in, patients were randomized to receive teverelix 60 mg (n = 41) or placebo (n = 40) subcutaneously on day 1 and day 3.

A Model-Informed Drug Development Approach to Design a Phase 3 Trial of Teverelix Drug Product in Advanced Prostate Cancer Patients with Increased Cardiovascular Risk.

Teverelix drug product (DP) is a parenteral gonadotropin-releasing hormone (GnRH) antagonist that has been successfully tested in phase 2 trials for hormone-sensitive advanced prostate cancer (APC) and benign prostatic hyperplasia (BPH). In previous APC trials, teverelix DP was administered as intramuscular (IM) and subcutaneous (SC) injections, using a loading dose and (in a single trial) a maintenance dose. Our objective was to derive an optimal dosing regimen for phase 3 clinical development, using a pharmacometrics modeling approach.

Efficacy, tolerability, and safety of teverelix DP in patients with advanced prostate cancer: A multicenter, open-label, phase 2 trial.

Background: Teverelix drug product (DP) is a novel injectable gonadotropin-releasing hormone antagonist.

Methods: An adaptive phase 2, open-label, multicenter trial was conducted in patients with advanced prostate cancer to evaluate the efficacy and safety of a combined subcutaneous (SC) and intramuscular (IM) loading dose regimen of teverelix DP of 120 mg SC + 120 mg IM (Group 1; N = 9) or 180 mg SC + 180 mg IM (Group 2; N = 41) administered at a single visit, followed by 6-weekly SC maintenance doses of 120 mg (Group 1) or 180 mg (Group 2), up to Day 168. The primary endpoint was the proportion of patients achieving castration levels with serum testosterone <0.

Safety, Pharmacokinetic and Pharmacodynamic Evaluation of Teverelix for the Treatment of Hormone-Sensitive Advanced Prostate Cancer: Phase 2 Loading-Dose-Finding Studies.

Teverelix drug product (DP) is a gonadotropin-releasing hormone antagonist in development for the treatment of patients with prostate cancer in whom androgen deprivation therapy is indicated. The aim of this paper is to present the results of five Phase 2 studies that assessed the pharmacokinetics, pharmacodynamics, efficacy and safety of different loading dose regimens of teverelix DP. Five single-arm, uncontrolled clinical trials were conducted in patients with advanced prostate cancer.

Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial.

Background: In the PREVAIL study, enzalutamide significantly improved clinical outcomes versus placebo in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).

Objective: To evaluate long-term benefits and risks of enzalutamide in the final prespecified PREVAIL analysis.

Design, Setting, And Participants: We conducted a final 5-yr survival analysis of PREVAIL in men with chemotherapy-naïve mCRPC from the enzalutamide (n = 689) and placebo (n = 693) arms.

Efficacy and Safety of Enzalutamide vs Bicalutamide in Younger and Older Patients with Metastatic Castration Resistant Prostate Cancer in the TERRAIN Trial.

Purpose: Enzalutamide significantly prolonged median progression-free survival vs bicalutamide in chemotherapy naïve men with metastatic castration resistant prostate cancer in the TERRAIN (Enzalutamide versus Bicalutamide in Castrate Men with Metastatic Prostate Cancer) trial. In this post hoc analysis we investigated the influence of age on the efficacy and safety of enzalutamide vs bicalutamide in this population.

Materials And Methods: Patients were randomized 1:1 to enzalutamide 160 mg per day or bicalutamide 50 mg per day.

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study.

Unlabelled: Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.

Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study.

Background: Enzalutamide is an oral androgen-receptor inhibitor that has been shown to improve survival in two placebo-controlled phase 3 trials, and is approved for patients with metastatic castration-resistant prostate cancer. The objective of the TERRAIN study was to compare the efficacy and safety of enzalutamide with bicalutamide in patients with metastatic castration-resistant prostate cancer.

Methods: TERRAIN was a double-blind, randomised phase 2 study, that recruited asymptomatic or minimally symptomatic men with prostate cancer progression on androgen-deprivation therapy (ADT) from academic, community, and private health-care provision sites across North America and Europe.

Development of enzalutamide for metastatic castration-resistant prostate cancer.

Prostate cancer is the most prevalent cancer among men in the Western world and a leading cause of cancer-related death among men. Within 5 years of initial diagnosis, approximately 10-20% of men will progress to metastatic castration-resistant prostate cancer (mCRPC). Often characterized by increased prostate-specific antigen and androgen receptor (AR) activity despite castrate levels of testosterone, mCRPC has a poor prognosis and causes significant deterioration in quality of life.

Low-dose tibolone (1.25 mg/d) does not affect muscle strength in older women.

Objective: More than 50% of all fractures occur in people without osteoporosis. Hormone therapy increases bone density, improves postural balance, and reduces fracture risk in postmenopausal women. It is unclear whether tibolone, a synthetic steroid hormone drug, can improve muscle strength.

Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial.

Background: Vasomotor symptoms and bone loss are complications frequently induced by adjuvant treatment for breast cancer. Tibolone prevents both side-effects, but its effect on cancer recurrence is unknown. The aim of this study was to show non-inferiority of tibolone to placebo regarding risk of recurrence in breast-cancer patients with climacteric complaints.

Tibolone low dose (1.25 mg/d) therapy and postural balance in elderly women.

Unlabelled: Most hip fractures occur in subjects without osteoporosis and are associated with a fall. Conventional menopausal hormone therapy (HT) improves postural balance, which might explain the rapid reduction in hip fracture risk. It is unclear whether tibolone improves postural balance, which might determine its effects on peripheral fracture risk.

Endometrial effects of tibolone in elderly, osteoporotic women.

Objective: To investigate endometrial effects of tibolone administered to postmenopausal women for 3 years.

Methods: Postmenopausal women (N=3,519) aged 60-85 years (mean 68 years) with a uterus and with osteoporosis were randomly assigned to receive tibolone orally, 1.25 mg per day, or identical placebo.