A Randomized, Double-Blind, Placebo-Controlled, First-Time-in-Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of GSK3389404 in Healthy Subjects.

GSK3389404 is a liver-targeted antisense oligonucleotide that inhibits synthesis of hepatitis B surface antigen and all other hepatitis B virus proteins. This first-in-human, randomized, double-blind, phase 1 study assessed the safety and pharmacokinetics of GSK3389404 administered subcutaneously (SC) in healthy subjects. Four single ascending-dose cohorts (10 mg, 30 mg, 60 mg, and 120 mg) and 3 multiple ascending-dose cohorts (30 mg, 60 mg, and 120 mg once weekly for 4 weeks) each comprised 6 subjects randomized to GSK3389404 and 2 subjects randomized to placebo.

Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in subjects with hepatic impairment.

JNJ-56914845 (GSK2336805) is a hepatitis C virus nonstructural protein 5A inhibitor under development for the treatment of chronic hepatitis C (CHC) infection. This open-label, parallel-group, 2-part study evaluated the pharmacokinetics and safety of a single oral 60 mg dose of JNJ-56914845 in 4 cohorts: healthy, mild, moderate, and severe hepatic impairment (n = 8/cohort). Severity of hepatic impairment was categorized using Child-Pugh score, and the healthy subjects were matched for age, sex, body mass index, and smoking status to the moderate hepatic impairment cohort.

Use of accelerometers in a large field-based study of children: protocols, design issues, and effects on precision.

Background: Objective methods can improve accuracy of physical activity measurement in field studies but uncertainties remain about their use.

Methods: Children age 11 years from the Avon Longitudinal Study of Parents and Children (ALSPAC), were asked to wear a uni-axial accelerometer (MTI Actigraph) for 7 days.

Results: Of 7159 children who attended for assessment, 5595 (78%) provided valid measures.

Calibration of an accelerometer during free-living activities in children.

Objective: The aims of this study were to develop an equation to predict energy expenditure and to derive cut-points for moderate and vigorous physical activity intensity from the Actigraph accelerometer output in children aged 12 years.

Methods: The children performed a series of activities (lying, sitting, slow walking, fast walking, hopscotch and jogging) while wearing an Actigraph and a portable metabolic unit. The sample was divided into a developmental and a validation group.

Intraindividual variation of objectively measured physical activity in children.

Purpose: This study examined the seasonal and intraindividual variation in objectively measured physical activity in 11- to 12-yr-olds.

Methods: Children were asked to wear a uniaxial accelerometer for 7 d four times throughout the course of about a year. A random-intercepts model was used to separate the inter- and intraindividual components of physical activity.