Systemic Safety in Ranibizumab-Treated Patients with Neovascular Age-Related Macular Degeneration: A Patient-Level Pooled Analysis.

Topic: This study evaluated the cardiovascular/cerebrovascular safety profile of ranibizumab 0.5 mg versus sham ± verteporfin in patients with neovascular age-related macular degeneration (nAMD). In addition, comparisons of ranibizumab 0.

The Systemic Safety of Ranibizumab in Patients 85 Years and Older with Neovascular Age-Related Macular Degeneration.

Objective: Ranibizumab safety is well established for treatment of neovascular age-related macular degeneration (nAMD), but less is known about the risk of systemic serious adverse events (SAEs), specifically among patients with heightened baseline risk due to age (≥85 years). This analysis examines whether patients ≥85 years of age versus those <85 years experience an increased risk of key systemic SAEs during intravitreal ranibizumab treatment for nAMD.

Design: Retrospective, pooled analysis of safety data from 5 phase III/IIIb multicenter randomized clinical trials in patients with nAMD: ANCHOR, MARINA, PIER, SAILOR, and HARBOR.

Vascular Safety of Ranibizumab in Patients With Diabetic Macular Edema: A Pooled Analysis of Patient-Level Data From Randomized Clinical Trials.

Importance: Patients with diabetic macular edema (DME) are at high risk of vascular complications, including stroke and myocardial infarction (MI). Concerns have been raised that intravitreal dosing of vascular endothelial growth factor inhibitors in DME could be associated with an increase in cardiovascular and cerebrovascular adverse events.

Objective: To evaluate the cardiovascular and cerebrovascular safety of ranibizumab, 0.

Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials.

Purpose: To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration.

Methods: Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios.

Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial.

Objective: To determine the efficacy and safety of ocrelizumab (OCR) with methotrexate (MTX) in MTX-naive rheumatoid arthritis (RA) patients.

Methods: In a randomised, double-blind, controlled trial, patients received placebo+MTX (MTX; n=210), OCR 200 mg×2+MTX (OCR 200; n=200) or OCR 500 mg×2+MTX (OCR 500; n=203). OCR/placebo (two intravenous infusions) was given on days 1 and 15, with fixed re-treatment scheduled at weeks 24/26, 52/54 and 76/78.

A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration.

Objective: To evaluate the safety and efficacy of intravitreal ranibizumab in a large population of subjects with neovascular age-related macular degeneration (AMD).

Design: Twelve-month randomized (cohort 1) or open-label (cohort 2) multicenter clinical trial.

Participants: A total of 4300 subjects with angiographically determined subfoveal choroidal neovascularization (CNV) secondary to AMD.

Comparison of QTinno, a fully automated electrocardiographic analysis program, to semiautomated electrocardiographic analysis methods in a drug safety study in healthy subjects.

Background: Improved automated methods for electrocardiographic (ECG) analysis are needed, particularly for drug development purposes.

Objectives: This study compared a novel fully automated method for ECG analysis (QTinno; NewCardio, Santa Clara, CA) to 2 semiautomated digital methods: global measurement from the earliest QRS onset to the latest T-wave offset on representative superimposed beats (global) and tangent measurement on 3 consecutive beats in one lead (tangent).

Methods: All 3 methods were used to determine uncorrected and rate-corrected QT interval duration (QT and QTcF) and related metrics in 1422 digital 12-lead ECGs from a phase 1 drug study.

Comparing methods of measurement for detecting drug-induced changes in the QT interval: implications for thoroughly conducted ECG studies.

Background: The aim of this study was to compare the reproducibility and sensitivity of four commonly used methods for QT interval assessment when applied to ECG data obtained after infusion of ibutilide.

Methods: Four methods were compared: (1) 12-lead simultaneous ECG (12-SIM), (2) lead II ECG (LEAD II), both measured on a digitizing board, (3) 3-LEAD ECG using a manual tangential method, and (4) a computer-based, proprietary algorithm, 12SL trade mark ECG Analysis software (AUT). QT intervals were measured in 10 healthy volunteers at multiple time points during 24 hours at baseline and after single intravenous doses of ibutilide 0.

Single oral dose safety, tolerability, and pharmacokinetics of PNU-96391 in healthy volunteers.

The safety, tolerability, and pharmacokinetics of PNU-96391, an orally active weak dopamine D2 receptor antagonist with modulatory properties of central dopaminergic function, was characterized. Fifty-three healthy normal volunteers were enrolled in this randomized, double-blinded, placebo-controlled, single-dose study. Subjects were assigned to single oral doses of placebo and 1, 3, 10, 30, 100, 150, and 200 mg PNU-96391.

Electrocardiographic identification of drug-induced QT prolongation: assessment by different recording and measurement methods.

Background: Careful assessment of QT interval prolongation is required before novel drugs are approved by regulatory authorities. The choice of the most appropriate method of electrocardiogram (ECG) acquisition and QT/RR interval measurement in clinical trials requires better understanding of the differences among currently available approaches. This study compared standard and Holter-derived 12-lead ECGs for utility in detecting sotalol-induced QT/QTc and RR changes.

The pharmacokinetics of linezolid are not affected by concomitant intake of the antioxidant vitamins C and E.

In vitro metabolism experiments have suggested a possible role for endogenous reactive oxygen species (ROS) in the in vivo clearance of linezolid, a synthetic antibiotic of the oxazolidinone class. This observation has resulted in the hypothesis that dietary antioxidant supplements might disturb the balance of ROS in vivo and thereby lower the clearance of linezolid. The purpose of this open-label, two-group parallel design study was to investigate whether continuous intake of widely used vitamin C or vitamin E will affect the pharmacokinetics of linezolid.

Valdecoxib, a COX-2-specific inhibitor, does not affect cardiac repolarization.

This double-blind, four-way crossover study assessed the effect of valdecoxib on the QTc interval duration in 25 male and 9 female healthy adults. Subjects received placebo or 40 mg, 80 mg, or 120 mg valdecoxib once daily for 5 days. Serial ECGs were obtained for 24 hours before the first treatment (baseline) and on the 5th day of each treatment.

Anticipatory anxiety in moderately to highly-anxious oral surgery patients as a screening model for anxiolytics: evaluation of alprazolam.

Alprazolam, a benzodiazepine anxiolytic, was evaluated in anxious patients prior to oral surgery. This population represents a possible acute screening model for novel anxiolytic agents. Healthy subjects, preselected for a moderate to high degree of dental anxiety based upon Corah's Dental Anxiety Scale, were enrolled in a three-arm parallel design study and randomly assigned to receive double-blind placebo (N=15), alprazolam 0.

Cardiovascular effect of almotriptan in treated hypertensive patients.

Objective: Our objective was to investigate the cardiovascular effects of almotriptan, a 5-hydroxytryptamine 1B/1D agonist, in treated patients with hypertension.

Methods: Twenty patients with hypertension controlled by medication received the following treatments in a randomized, double-blind, crossover design: one placebo tablet, one 12.5-mg almotriptan tablet, and one 25-mg almotriptan tablet.