Dose-response effects on HbA and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial.

Aims/hypothesis: The aim of this study was to assess the dose-response effects of the subcutaneous glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide (BI 456906) on HbA levels and bodyweight reduction.

Methods: This Phase II, multicentre, randomised, double-blind, parallel-group, placebo-controlled study, conducted in clinical research centres, assessed survodutide in participants aged 18-75 years with type 2 diabetes, an HbA level of 53-86 mmol/mol (7.0-10.

Effects of Single and Multiple Ascending Doses of BI 1358894 in Healthy Male Volunteers on Safety, Tolerability and Pharmacokinetics: Two Phase I Partially Randomised Studies.

Introduction: The transient receptor potential canonical (TRPC) ion channels have been implicated in the pathophysiology of major depressive disorder (MDD), and TRPC inhibition has been shown to reduce depressive-like behaviour in rodent models of depression. BI 1358894, a small-molecule inhibitor of TRPC ion channels, is currently being developed for the treatment of MDD.

Objective: Two phase I studies assessed the safety, tolerability, and pharmacokinetics (PK) of oral BI 1358894 in fed and fasted states following a single ascending dose (SAD) [NCT03210272/1402-0001] and multiple ascending doses (MAD) [NCT03754959/1402-0002] in healthy male volunteers.

Bioequivalence of Intravenous Alteplase from Two Different Manufacturing Processes in Healthy Male Volunteers: Results from a Two-Stage, Adaptive-Design Study.

Objective: Alteplase is a recombinant tissue plasminogen activator used for thrombolytic treatment in several indications and is currently approved in Europe under the brand name Actilyse. The current manufacturing process for alteplase was recently modified to meet increasing global demands. The aim of this randomized, open-label, adaptive two-stage design, two-way crossover study was to establish bioequivalence of alteplase derived from the two manufacturing processes (modified versus current).

A Phase 1 Study of mTORC1/2 Inhibitor BI 860585 as a Single Agent or with Exemestane or Paclitaxel in Patients with Advanced Solid Tumors.

This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5-300 mg/day; Arm A), BI 860585 (40-220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80-220 mg/day; Arm C) with 60-80 mg/m/week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD.

A case control study of sarcosine as an early prostate cancer detection biomarker.

Background: Sarcosine has been investigated as a prostate cancer biomarker with mixed results concerning its predictive power. We performed a case-control evaluation of the predictive value of serum sarcosine for early detection in a population-based cohort of men undergoing prostate-specific antigen (PSA) screening.

Methods: For analysis we used 251 cancer cases and 246 age-matched non-cancer cases from the San Antonio Biomarkers Of Risk (SABOR) screening study.

Precision Medicine in Active Surveillance for Prostate Cancer: Development of the Canary-Early Detection Research Network Active Surveillance Biopsy Risk Calculator.

Background: Men on active surveillance (AS) face repeated biopsies. Most biopsy specimens will not show disease progression or change management. Such biopsies do not contribute to patient management and are potentially morbid and costly.

Prostate Cancer Prevention Trial risk calculator 2.0 for the prediction of low- vs high-grade prostate cancer.

Objective: To modify the Prostate Cancer Prevention Trial risk calculator (PCPTRC) to predict low- vs high-grade (Gleason grade≥7) prostate cancer and incorporate percent free-prostate-specific antigen (PSA).

Methods: Data from 6664 Prostate Cancer Prevention Trial placebo arm biopsies (5826 individuals), where prostate-specific antigen and digital rectal examination results were available within 1 year before the biopsy and PSA was ≤10 ng/mL, were used to develop a nominal logistic regression model to predict the risk of no vs low-grade (Gleason grade<7) vs high-grade cancer (Gleason grade≥7). Percent free-PSA was incorporated into the model based on likelihood ratio analysis of a San Antonio Biomarkers of Risk cohort.