Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT).

Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial. Methods The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial ( ClinicalTrial.

SELECT-2: a phase II, double-blind, randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer.

Background: Combination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC.

Patients And Methods: Patients who had disease progression after first-line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.

Medication-taking experiences in attention deficit hyperactivity disorder: a systematic review.

Background: Although attention deficit hyperactivity disorder (ADHD) is a common condition for which pharmacotherapy is considered an effective treatment, guidelines on the treatment of ADHD have been challenging to implement. Considering the views of patients and caregivers involved in medication-taking could help shed light on these challenges.

Objective: This review combines the findings of individual studies of medication-taking experiences in ADHD in order to guide clinicians to effectively share decisions about treatment.

Pharmacokinetics and pharmacogenetics of the MEK1/2 inhibitor, selumetinib, in Asian and Western healthy subjects: a pooled analysis.

Purpose: Emerging data on selumetinib, a MEK1/2 inhibitor in clinical development, suggest a possible difference in pharmacokinetics (PK) between Japanese and Western patients. This pooled analysis sought to assess the effect of ethnicity on selumetinib exposure in healthy Western and Asian subjects, and to identify any association between genetic variants in the UGT1A1, CYP2C19 and ABCG2 genes and observed differences in selumetinib PK.

Methods: A pooled analysis of data from ten Phase I studies, one in Asian subjects (encompassing Japanese, non-Japanese Asian and Indian Asian subjects) and nine in Western subjects, was conducted.

Data Science Solution to Event Prediction in Outsourced Clinical Trial Models.

Late phase clinical trials are regularly outsourced to a Contract Research Organisation (CRO) while the risk and accountability remain within the sponsor company. Many statistical tasks are delivered by the CRO and later revalidated by the sponsor. Here, we report a technological approach to standardised event prediction.

Defining acceptable epidemiology ranges in donor populations based on the contamination risk of finished plasma-derived products.

Background: For a given plasma-derived product, the risk of final product contamination by hepatitis B virus, hepatitis C virus and human immunodeficiency virus depends upon the epidemiology in the donor population, the virus load in a donation, the product yield and the effective virus reduction capacity in manufacturing.

Study Design And Methods: A Monte Carlo simulation model was developed to estimate the risk of virus contamination of a final product resulting from virus contamination of plasma pools for fractionation. The model was run for both source and recovered plasma at various incidence rates for the three viruses to determine virus loads in minipools and fractionation pools resulting from donations with virus levels below test sensitivities.

Characterization of renal biomarkers for use in clinical trials: biomarker evaluation in healthy volunteers.

Background: Several preclinical urinary biomarkers have been qualified and accepted by the health authorities (US Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency) for detecting drug-induced kidney injury during preclinical toxicologic testing. Validated human assays for many of these biomarkers have become commercially available, and this study was designed to characterize some of the novel clinical renal biomarkers. The objective of this study was to evaluate clinical renal biomarkers in a typical Phase I healthy volunteer population to determine confidence intervals (pilot reference intervals), intersubject and intrasubject variability, effects of food intake, effect of sex, and vendor assay comparisons.

Vandetanib inhibits both VEGFR-2 and EGFR signalling at clinically relevant drug levels in preclinical models of human cancer.

Vandetanib is a multi-targeted receptor tyrosine kinase inhibitor that is in clinical development for the treatment of solid tumours. This preclinical study examined the inhibition of two key signalling pathways (VEGFR-2, EGFR) at drug concentrations similar to those achieved in the clinic, and their contribution to direct and indirect antitumour effects of vandetanib. For in vitro studies, receptor phosphorylation was assessed by Western blotting and ELISA, cell proliferation was assessed using a cell viability endpoint, and effects on cell cycle determined using flow cytometry.

Effect of pretreatment with atenolol and nifedipine on ZD6126-induced cardiac toxicity in rats.

Antivascular agents that act by destabilizing microtubules, such as ZD6126 (N-acetylcolchinol-O-phosphate), are associated with adverse cardiovascular effects, including transient hypertension, cardiac ischemia, myocardial infarction, and increases in circulating levels of markers of cardiac damage (e.g., troponins).

School-based clinic use and other factors affecting adolescent contraceptive behavior.

Adolescent risk taking, preventive behavior, and contraceptive use were investigated using a self-administered questionnaire in a sample of 260 inner-city high school students targeted by a school-based health clinic. Multivariate models consisting of individual and environmental variables significantly predicted sexual activity and contraceptive use. Older age at first intercourse, higher number of welfare benefits received by the household (including Medicaid, food stamps, and free or reduced price lunch), and use of the school-based clinic were significant positive predictors of more frequent contraceptive use by adolescents.

Integrated school and community programs.

Collaboration and coordination among school nurses, health teachers, guidance counselors, food service directors, principals, administrators, parents, and community agencies have the potential to upgrade school health programs. Benefits derived from an integrated school and community program are documented. Three models that have effectively brought together schools and community agencies are described.