First Administration of the Fc-Attenuated Anti-beta Amyloid Antibody GSK933776 to Patients with Mild Alzheimer's Disease: A Randomized, Placebo-Controlled Study

Objectiv

Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of beta-amyloid (1-42) in human cerebrospinal fluid

Introduction Available assays for quantitation of the Alzheimer's disease (AD) biomarker amyloid‐beta 1–42 (Aβ [1–42]) in cerebrospinal fluid demonstrate significant variability and lack of standardization to reference measurement procedures (RMPs). We report analytical performance data for the novel Elecsys β‐amyloid (1–42) assay (Roche Diagnostics). Methods Lot‐to‐lot comparability was tested using method comparison. Performance parameters were measured according to Clinical & Laboratory Standards Institute (CLSI) guidelines. The assay was standardized to a Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved RMP. Results Limit of quantitation was 0.995; bias in medical decision area <2%). Repeatability coefficients of variation (CVs) were 1.0%–1.6%, intermediate CVs were 1.9%–4.0%, and intermodule CVs were 1.1%–3.9%. Estimated total reproducibility was 2.0%–5.1%. Correlation with the RMP was good (Pearson's r, 0.93). Discussion The Elecsys β‐amyloid (1–42) assay has high analytical performance that may improve biomarker‐based AD diagnosis

Rapid Endovascular Catheter Core Cooling combined with cold saline as an Adjunct to Percutaneous Coronary Intervention For the Treatment of Acute Myocardial Infarction (The CHILL-MI trial).

Hypothermia has been reported to reduce infarct size (IS) in patients with ST segment elevation myocardial infarction (STEMI). We aimed to confirm the cardioprotective effects of hypothermia using a combination of cold saline and endovascular cooling

GSK933776 plasma pharmacodynamics.

<p>A) Geometric mean plasma Aβ concentration–time plots over the three dosing intervals (semi-log plot). Plasma levels of total Aβ42 and Aβ increased whereas plasma levels of free Aβ decreased in dose-dependent manner. Peak:trough ratios for Aβ decreased with increasing dose of GSK933776. B) Week 12 ratio to baseline for CSF Aβ (Aβ1–42 and AβX–42) concentrations. Presented as individual values and mean (95%CI). There were no significant changes from baseline for Aβ1–42 or AβX–42.</p

Summary of most frequently reported adverse events.

<p>SD = single dose; RD = repeat dose.</p><p>²Amyloid-related imaging abnormality-hemorrhage (ARIA-H)</p><p>¹Amyloid-related imaging abnormality-edema (ARIA-E);</p><p>Summary of most frequently reported adverse events.</p

Summary of patients’ baseline characteristics.

<p>SD = single dose; RD = repeat dose; SE = standard error.</p><p>³Three patients participated in two dose levels of the single dose study and therefore the PGx sample was collected at the first dosing level in which they participated and not the second dosing level. <i>APOE</i> ε4 overall carriage frequency was calculated using the PGx population (n = 15), i.e., patients who participated in more than one dosing level were only taken into account once.</p><p>²Six patients participated in part A and re-entered part B. Therefore the pharmacogenetic (PGx) sample was collected when the patients participated in part A and no PGx sample was collected during part B. <i>APOE</i> ε4 overall carriage frequency was calculated using the PGx population (n = 44), i.e., patients who participated in both parts were only taken into account once.</p><p>¹Values ranged from 20 to 26 for all patients except one, who scored 28.</p><p>Summary of patients’ baseline characteristics.</p

GSK933776 plasma pharmacokinetics.

<p>Time-course of plasma concentrations of GSK933776 by dose: medians (lines) and individual data (dots). LLQ is 100 ng/mL for the 0.1 mg/kg dose and 5 μg/mL for the 1, 3, and 6 mg/kg doses. SD = single dose; RD = repeat dose. Maximum plasma concentrations increased with dose.</p