Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease.

Unlabelled: 600 patients aged ≥18 years will be randomised in a 1:1 ratio to nintedanib or placebo. Patients with diagnosis of IPF will be excluded. The study population will be enriched with two-thirds having a usual interstitial pneumonia-like pattern on HRCT.

Effect of Nintedanib in Subgroups of Idiopathic Pulmonary Fibrosis by Diagnostic Criteria.

Rationale: In the absence of a surgical lung biopsy, patients diagnosed with idiopathic pulmonary fibrosis (IPF) in clinical practice could participate in the INPULSIS trials of nintedanib if they had honeycombing and/or traction bronchiectasis plus reticulation, without atypical features of usual interstitial pneumonia (UIP), on high-resolution computed tomography (HRCT). Thus, the patients in these trials represented patients with definite UIP and a large subgroup of patients with possible UIP.

Objectives: To investigate the potential impact of diagnostic subgroups on the progression of IPF and the effect of nintedanib.

Tiotropium Respimat in cystic fibrosis: Phase 3 and Pooled phase 2/3 randomized trials.

Background: Tiotropium Respimat improved lung function in a phase 2 trial in patients with cystic fibrosis (CF). We investigated its efficacy and safety in a phase 3 trial, including a pre-specified pooled analysis of the phase 2 and 3 trials.

Methods: 12-week, randomized, double-blind, placebo-controlled trial of tiotropium Respimat 5 μg once daily in patients with CF (N=463).

Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis.

Background: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis.

Methods: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis.

Design of the INPULSIS™ trials: two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis.

Background: Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF). Data from the Phase II TOMORROW study suggested that nintedanib 150 mg twice daily had clinical benefits with an acceptable safety profile.

Methods: The INPULSIS™ trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150 mg twice daily with placebo in patients with IPF.

Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis.

Background: Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism (VTE) in a previous trial. We undertook this study to extend those findings.

Methods And Results: In a randomized, double-blind, double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days, we compared dabigatran 150 mg twice daily with warfarin.

Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation.

Background: The efficacy of afatinib, an irreversible ErbB Family Blocker, was evaluated in patients who had 1 of 4 categories of solid tumors with epidermal growth factor receptor/human epidermal growth factor receptor 2 (EGFR/HER2) gene amplification or EGFR-activating mutations.

Methods: Patients with previously treated but ErbB inhibitor-naive esophagogastric, biliary tract, urothelial tract, or gynecologic cancers (lung cancers were excluded) harboring EGFR/HER2 gene amplification or high polysomy were identified by fluorescence in situ hybridization (FISH). Tumors were also screened for EGFR mutations.

Effective strategies for management of hypertension after vascular endothelial growth factor signaling inhibition therapy: results from a phase II randomized, factorial, double-blind study of Cediranib in patients with advanced solid tumors.

PURPOSE Hypertension is a commonly reported adverse effect after administration of vascular endothelial growth factor (VEGF) inhibitors. Cediranib is a highly potent and selective VEGF signaling inhibitor of all three VEGFRs. This study prospectively investigated hypertension management to help minimize dose interruptions/reductions to maximize cediranib dose intensity.

Long-term efficacy and safety of rosuvastatin 40 mg in patients with severe hypercholesterolemia.

Patients with elevated low-density lipoprotein (LDL) cholesteral levels are at high risk of cardiovascular events but are often undertreated and fail to achieve lipid goals. This open-label, noncomparative, multicenter study assessed efficacy and safety of rosuvastatin 40 mg for < or =96 weeks in 1,380 patients with severe hypercholesterolemia, including heterozygous familial hypercholesterolemia. Patients > or =18 years old with fasting LDL cholesterol > or =190 and < or =260 mg/dl and triglycerides <400 mg/dl entered a 6-week dietary lead-in, before receiving rosuvastatin 40 mg for 48 weeks.

Comparison of short-term renal effects and efficacy of rosuvastatin 40 mg and simvastatin 80 mg, followed by assessment of long-term renal effects of rosuvastatin 40 mg, in patients with dyslipidemia.

Background: An open-label, randomized, multinational, parallel-group trial compared the short-term (6-week) renal effects of rosuvastatin 40 mg and simvastatin 80 mg in patients with hypercholesterolemia. Most patients (93%) then entered an optional open-label extension (OLE) to assess long-term (up to 72 weeks) renal effects of rosuvastatin.

Methods: After dietary lead-in, 626 patients were randomized to rosuvastatin or simvastatin for 6 weeks, followed by an optional, single-arm OLE to assess longer-term effects of rosuvastatin on renal function, safety, and efficacy.

Comparison of the effects of high doses of rosuvastatin versus atorvastatin on the subpopulations of high-density lipoproteins.

Atorvastatin and rosuvastatin are both highly effective in decreasing low-density lipoprotein cholesterol and triglyceride levels. However, rosuvastatin was shown to be more effective in increasing high-density lipoprotein (HDL) cholesterol levels. The purpose of the study is to compare the effects of daily doses of rosuvastatin 40 mg with atorvastatin 80 mg during a 6-week period on HDL subpopulations in 306 hyperlipidemic men and women.