Safety and tolerability of long-term treatment with darolutamide in patients with metastatic castration-resistant prostate cancer.

Background: In patients with metastatic castration-resistant prostate cancer, darolutamide was well tolerated for 25 months, but minimal long-term safety data are available.

Methods: Treatment-emergent adverse events (TEAEs) for patients receiving darolutamide for a median of 38 months (n = 13) are described in this pooled analysis of individual patient data from phase 1/2 studies.

Results: All patients reported TEAEs (mostly grade 1/2).

Pregabalin Alleviates Anxiety and Fear in Cats during Transportation and Veterinary Visits-A Clinical Field Study.

Cats frequently suffer from anxiety related to travel and veterinary visits. One sequela is avoidance of veterinary visits and lack of adequate veterinary care. The objective of this study was to test clinical efficacy and safety of a novel formulation of a pregabalin 50 mg/mL oral solution for alleviation of anxiety and fear in cats during transport and veterinary visits.

Nanoparticle-based oral formulation can surprise you with inferior in vivo absorption in humans.

Particle size reduction leads to an increase in the drug dissolution rate, which in turn can lead to a substantial increase in the bioavailability of a poorly soluble compound. To improve bioavailability, a practically insoluble investigational drug, ODM-106, was nanomilled and capsule formulations with three different drug amounts were prepared for the first-in-man study. Fast in vitro dissolution was achieved from all the capsules containing different amounts of drug nanoparticles but in the clinical study, surprisingly, low bioavailability was observed from the highest capsule strength (100 mg) in comparison to a lower strength (10 mg).

Tasipimidine-the pharmacological profile of a novel orally active selective α-adrenoceptor agonist.

The pharmacological profile of tasipimidine, a novel orally active α-adrenoceptor agonist developed for situational anxiety and fear in dogs, was studied in various in vitro and in vivo models. In the cell assays, tasipimidine demonstrated binding affinity and full agonism on the human α-adrenoceptors with a pEC50 of 7.57, while agonism on the α-and α-adrenoceptors and the rodent α-adrenoceptor was weaker, resulting in pEC50 values of 6.

Efficacy of a Single Dose of Pregabalin on Signs of Anxiety in Cats During Transportation-A Pilot Study.

The aim of this clinical pilot study was to evaluate the dosage, efficacy, and clinical safety of a single oral dose of pregabalin in cats that experience fear and anxiety when placed into a carrier and transported by car. Thirteen client-owned cats were enrolled in a blinded, randomized, crossover study with three treatment days approximately 1 week apart. The cats were assigned to receive pregabalin oral solution at dosages of 5 and 10 mg/kg and placebo in a randomized order, one treatment per week.

Dexmedetomidine oromucosal gel reduces fear and anxiety in dogs during veterinary visits: A randomised, double-blind, placebo-controlled clinical pilot study.

Introduction: Many dogs are anxious and/or fearful in veterinary clinics and exhibit avoidant and/or defensive behaviour. The purpose of pharmacological interventions is to reduce anxiety and to enable patient-friendly, low stress physical examination and procedures.

Materials And Methods: This was a randomised, double-blind, placebo-controlled, parallel-group, multicentre, clinical-field study.

Use of Detomidine Oromucosal Gel for Alleviation of Acute Anxiety and Fear in Horses: A Pilot Study.

The aim of this randomized, double-blind, placebo-controlled, parallel group clinical field study was to evaluate the effect of detomidine oromucosal gel in alleviating anxiety and fear in horses. Sixteen horses with a history of acute anxiety and fear associated with firework-related noise entered the study. On New Year's Eve, eight horses were treated with 30 μg/kg detomidine gel and eight horses with placebo gel.

First-in-human Phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours.

Background: Bromodomain and extra-terminal domain (BET) proteins are reported to be epigenetic anti-cancer drug targets. This first-in-human study evaluated the safety, pharmacokinetics and preliminary anti-tumour activity of the BET inhibitor ODM-207 in patients with selected solid tumours.

Methods: This was an open-label Phase 1 study comprised of a dose escalation part, and evaluation of the effect of food on pharmacokinetics.

Safety and Antitumour Activity of ODM-201 (BAY-1841788) in Chemotherapy-naïve and CYP17 Inhibitor-naïve Patients: Follow-up from the ARADES and ARAFOR Trials.

Background: ODM-201, a new androgen receptor antagonist for treatment of metastatic castration-resistant prostate cancer (mCRPC), demonstrated antitumour activity and acceptable tolerability in phase 1/2 trials.

Objective: To determine the antitumour activity and safety profile of extended treatment with ODM-201 in men with mCRPC.

Design, Setting, And Participants: ARADES and ARAFOR trials with ODM-201 enrolled chemotherapy-naïve and CYP17 inhibitor (CYP17i)-naïve mCRPC patients.

Safety and Antitumour Activity of ODM-201 (BAY-1841788) in Castration-resistant, CYP17 Inhibitor-naïve Prostate Cancer: Results from Extended Follow-up of the ARADES Trial.

Background: Patients with castration-resistant prostate cancer (CRPC) had extended responses to the androgen receptor antagonist ODM-201, in phase 1/2 studies.

Objective: To evaluate the safety and antitumour activity of prolonged ODM-201 treatment in patients with CRPC.

Design, Setting, And Participants: The ARADES trial was a multicentre phase 1 (dose escalation) and phase 2 (dose expansion) trial; 134 patients with CRPC were stratified by previous chemotherapy to receive ODM-201.

Bone Scan Index and Progression-free Survival Data for Progressive Metastatic Castration-resistant Prostate Cancer Patients Who Received ODM-201 in the ARADES Multicentre Study.

Background: ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects.

Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial.

Background: ODM-201 is a novel androgen receptor (AR) inhibitor designed to block the growth of prostate cancer cells through high-affinity binding to the AR and inhibition of AR nuclear translocation. This trial assessed ODM-201's safety, pharmacokinetics, and activity in men with metastatic castration-resistant prostate cancer.

Methods: The ARADES trial is an open-label phase 1-2 trial undertaken in 23 hospitals across Europe and USA with ongoing long-term follow-up.

Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs.

Objective: To compare postoperative analgesia provided by a constant rate infusion (CRI) of dexmedetomidine (DMED) to that of a well-established positive control [morphine (MOR)] in critically ill dogs. The sedative, cardiorespiratory effects and clinical safety of a 24-hour DMED CRI were also evaluated.

Study Design: Prospective, randomised, blinded, positive-controlled parallel-group clinical study.

Dexmedetomidine constant rate infusion for 24 hours during and after propofol or isoflurane anaesthesia in dogs.

Objective: To evaluate cardiovascular and respiratory effects and pharmacokinetics of a 24-hour intravenous constant rate infusion (CRI) of dexmedetomidine (DMED) during and after propofol (PRO) or isoflurane (ISO) anaesthesia in dogs.

Study Design: Prospective, randomized, cross-over study.

Animals: Ten healthy adult Beagles.

Evaluation of the clinical efficacy and safety of dexmedetomidine or medetomidine in cats and their reversal with atipamezole.

Objective: To evaluate and compare the clinical effects of dexmedetomidine (DEX) and medetomidine (MED) in cats, and their reversal with atipamezole (ATI). Study design Prospective blinded randomized multi-centre clinical trial. Animals One hundred and twenty client-owned cats.