Safety and pharmacodynamic dose response of short-term prednisone in healthy adult subjects: a dose ranging, randomized, placebo-controlled, crossover study.

Background: Glucocorticoids (GCs), such as prednisone, are the standard of care for several inflammatory and immunologically mediated diseases, but their chronic systemic administration is severely limited by serious adverse effects that are both dose and time dependent. Short-term treatment (7-14 days) with oral prednisone is used for many acute inflammatory and allergic conditions. This study was conducted to characterize the safety and pharmacodynamic (PD) dose-response of a 7-day course of oral prednisone on biomarkers of GC receptor agonism.

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ASP2408, a Potent Selective T-Cell Costimulation Modulator After Single and Multiple Ascending Doses in Healthy Volunteers and RA Patients.

ASP2408 is a next-generation anti-cytotoxic T lymphocyte antigen-4 fusion protein engineered for improved CD86 binding affinity as a treatment for rheumatoid arthritis (RA). In 72 healthy subjects (n = 6/treatment), ASP2408 was administered as single ascending doses intravenously at 0.003 to 10.

A Phase 1 Dose-Escalation Study of ASP2409, a Selective T-Cell Costimulation Inhibitor, in Stable Rheumatoid Arthritis Patients on Methotrexate Therapy.

ASP2409 represents a new class of CTLA4-Ig molecules with higher binding avidity and selectivity to CD86. This first-in-human study was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ASP2409 in stable rheumatoid arthritis patients on methotrexate therapy with a randomized, double-blind, placebo-controlled dose-escalation study design. Patients were enrolled and randomized in each of 8 dose-escalation cohorts ranging from 0.

Safety profile and tolerability of up to 1 year of pregabalin treatment in 3 open-label extension studies in patients with fibromyalgia.

Background: Pain relief and an acceptable safety profile have been reported in randomized controlled trials (RCTs) of pregabalin in the treatment of fibromyalgia (FM) for up to 14 weeks.

Objective: To evaluate the safety profile and tolerability of pregabalin (75-300 mg BID) treatment for up to 1 year in patients with FM.

Methods: Twelve-week data were pooled from 3 open-label extension studies of pivotal RCTs.

Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial.

Introduction: The purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX).

Methods: This phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks.

LY315920NA/S-5920, a selective inhibitor of group IIA secretory phospholipase A2, fails to improve clinical outcome for patients with severe sepsis.

Objective: Group IIA secretory phospholipase A2 (sPLA2-IIA), released during inflammation, is increased in severe sepsis, and plasma levels are inversely related to survival. In a previous study, a selective inhibitor of sPLA2-IIA (LY315920NA/S-5920) was well tolerated and appeared to improve survival in a subgroup of patients who received the drug within 24 hrs of first sepsis-induced organ failure. This study was designed to determine whether improvement in survival could be confirmed in a larger patient population meeting the characteristics of that subgroup.

Impact of a soluble phospholipase A2 inhibitor on inhaled allergen challenge in subjects with asthma.

The possible roles of secretory phospholipases A2 (sPLA2) in asthma include the release of arachidonic acid from cellular membranes, generation of lysophospholipids, sPLA2-mediated activation of cPLA2 with increased leukotriene production, and surfactant degradation. LY333013 is a potent inhibitor of sPLA2. This study examined the impact of two doses of LY333013 vs.

Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study.

Objective: Neutrophil elastase is believed to be an important mediator of acute lung injury. Sivelestat (ONO-5046, Elaspol) is a small molecular weight inhibitor of neutrophil elastase. The primary objectives of this study were to determine whether sivelestat would reduce 28-day all-cause mortality or increase the number of ventilator-free days (days alive and free from mechanical ventilation from day 1 to day 28) compared with placebo in mechanically ventilated patients with acute lung injury.

Neutrophil elastase and acute lung injury: prospects for sivelestat and other neutrophil elastase inhibitors as therapeutics.

Objectives: To review the evidence and rationale that suggest that neutrophil elastase (NE) may contribute to the development of acute lung injury (ALI) and the acute respiratory distress syndrome. To review selected preliminary data regarding the effectiveness of NE inhibition in animals, in in vitro models, and in patients with ALI.

Data Sources: The published literature and observations provided by Ono Pharmaceutical and Eli Lilly investigators and their colleagues.