Mortality and adverse events with brand and generic clopidogrel in the US Food and Drug Administration Adverse Event Reporting System.

Aims: Clopidogrel is commonly used even after expiring patents. The brand clopidogrel (BC) was dealt by single company, while numerous manufacturers produce generic clopidogrel (GC). There are no convincing data to compare the safety of different formulations.

Aganirsen antisense oligonucleotide eye drops inhibit keratitis-induced corneal neovascularization and reduce need for transplantation: the I-CAN study.

Objective: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation.

Design: Multicenter, double-masked, randomized, placebo-controlled phase III study.

Safety, tolerability and pharmacokinetics of intravaginal pentamycin.

Background/aims: Intravaginal pentamycin is a polyene macrolide with a broad spectrum of antimicrobial activity and is effective in various forms of infectious vaginitis. We evaluated the safety, tolerability and pharmacokinetics of escalating doses of this product.

Methods: Nineteen healthy volunteers were randomized to receive double blind one of five doses of intravaginal pentamycin (3, 10, 30, 60 or 100 mg) or the corresponding dose of pentamycin vehicle daily for 6 days.

Impact of time to therapy and presence of collaterals on the efficacy of FX06 in acute ST elevation myocardial infarction: a substudy of the F.I.R.E., the Efficacy of FX06 in the prevention of myocardial reperfusion injury trial.

Aims: To determine whether the efficacy of FX06 was dependent upon the timing of reperfusion therapy or the presence of collaterals in the Efficacy of FX06 in the prevention of myocardial reperfusion injury (F.I.R.

Relation of cardiac troponin I measurements at 24 and 48 hours to magnetic resonance-determined infarct size in patients with ST-elevation myocardial infarction.

Levels of circulating cardiac troponin I (cTnI) or T are correlated to extent of myocardial destruction after an acute myocardial infarction. Few studies analyzing this relation have employed a second-generation cTnI assay or cardiac magnetic resonance (CMR) as the imaging end point. In this post hoc study of the Efficacy of FX06 in the Prevention of Mycoardial Reperfusion Injury (F.

Tolerability and safety of GS-101 eye drops, an antisense oligonucleotide to insulin receptor substrate-1: a 'first in man' phase I investigation.

Aims: GS-101 (GeneSignal, Epalinges, Switzerland) is an antisense oligonucleotide that inhibits the expression of the scaffold protein insulin receptor substrate-1 (IRS-1). Inhibition of IRS-1 results in the prevention of neovascular growth and was shown to prevent the angiogenic process in preclinical in vitro and in vivo experiments. There is therefore a strong therapeutic rational for targeting angiogenesis in pathological neovascularization.

GS-101 antisense oligonucleotide eye drops inhibit corneal neovascularization: interim results of a randomized phase II trial.

Purpose: Pathologic corneal neovascularization not only reduces corneal transparency and visual acuity, but also is one of the most significant preoperative and postoperative risk factors for graft rejection after corneal transplantation. The aim of this study was to test tolerability and efficacy of gene signal (GS)-101 eye drops, an antisense oligonucleotide against insulin receptor substrate-1, versus placebo on inhibition of progressive corneal neovascularization.

Design: Randomized, double-blind, multicenter, phase II clinical study.

Effect of intravenous FX06 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) trial.

Objectives: The purpose of this study was to investigate whether FX06 would limit infarct size when given as an adjunct to percutaneous coronary intervention.

Background: FX06, a naturally occurring peptide derived from human fibrin, has been shown to reduce myocardial infarct size in animal models by mitigating reperfusion injury.

Methods: In all, 234 patients presenting with acute ST-segment elevation myocardial infarction were randomized in 26 centers.

Rationale and design of the 'F.I.R.E.' study. A multicenter, double-blind, randomized, placebo-controlled study to measure the effect of FX06 (a fibrin-derived peptide Bbeta(15-42)) on ischemia-reperfusion injury in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

Immediate reopening of acutely occluded coronary arteries via primary percutaneous coronary intervention (PCI) is the treatment of choice to salvage the ischemic myocardium in the setting of ST-segment elevation myocardial infarction (STEMI). However, the sudden re-initiation of blood flow achieved with PCI can lead to a local acute inflammatory response with further endothelial and myocardial damage. This phenomenon, described as 'reperfusion injury', has been recognized for several decades, yet no pharmacologic intervention has so far succeeded in reducing myocardial damage linked to reperfusion.

Clopidogrel loading dose regimens: kinetic profile of pharmacodynamic response in healthy subjects.

Clopidogrel, a potent novel platelet ADP-receptor antagonist, induces a significant inhibition of ADP-induced platelet aggregation. Maximum inhibition of 40 to 50% is observed 2 to 5 hours after a single 400 mg dose. The same level of inhibition is achieved with 75 mg once daily at steady state, i.

Immunogenicity of a recombinant Pre-S2-containing hepatitis B vaccine versus plasma-derived vaccine administered as a booster.

GenHevac B Pasteur is a recombinant hepatitis B vaccine derived from a mammalian cell line and containing HBs as well as pre-S2 antigens. Its immunogenicity was compared to that of the plasma-derived vaccine Hevac B Pasteur in a population primovaccinated 5.5 years earlier with four injections of the same plasma vaccine.

Anti-pre-S2 antibody response in subjects vaccinated against hepatitis B and in naturally immunized subjects.

Serum samples from individuals immunized with a pepsinized or non-pepsinized vaccine and from patients who had recovered from acute hepatitis B or who developed a chronic form of the disease, were analysed for the presence of antibody against the pre-S2 epitope of the hepatitis B virus. Anti-pre-S2 antibody was absent in all but one individual immunized with the pepsinized vaccine. Thirty-eight percent of the subjects who responded by anti-HBs production to the non-pepsinized preparation showed anti-pre-S2 antibody one year after complete vaccination.

Monotherapy with valproate in primary generalized epilepsies.

Sodium valproate enteric-coated tablets were administered as monotherapy to 118 patients (median age, 19 years) with primary generalized epilepsies. More than half (56%) of these patients were transferred from prior drug therapy, most of them because of inadequate seizure control, and some because of adverse effects. Seventy-one percent of the patients experienced tonic-clonic seizures, either alone or in combination with other types of seizures, principally absences.