A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis.50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo.Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone.In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone. @ERSpublications Nintedanib had acceptable safety and tolerability in Japanese patients with IPF

The distinctive clinical features and chronological change were seen in Japanese ulcerative colitis patients in recent years. Our data can help understand clinical aspects of ulcerative colitis patients in Asia, where the incidence of ulcerative colitis is still increasing.

Background and objective: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia. Nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo in patients with IPF in two replicate trials (INPULSIS

Background and objective: In the two-replicate randomized Phase III INPULSIS® trials in patients with idiopathic pulmonary fibrosis (IPF), nintedanib 150 mg bd significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo. The key secondary endpoints were time to first investigatorreported acute exacerbation and change from baseline in St George's Respiratory Questionnaire total score, both over 52 weeks. Here, we assessed the effect of nintedanib in Asian patients. Methods: Pre-specified subgroup analyses of the effect of nintedanib on the primary and key secondary endpoints in Asian versus White patients were undertaken based on pooled data from the two INPULSIS ® trials. Safety data were analyzed descriptively. Results: Of the treated patients, 322 were Asian (nintedanib n = 194; placebo n = 128) and 608 were White (nintedanib n = 360; placebo n = 248). In Asian patients, the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 94.1 mL/year (95% CI: 33.7, 154.6). The treatment effect of nintedanib on the annual rate of decline in FVC in Asian and White patients was similar (treatment-by-subgroup interaction P = 0.72) and consistent with the overall population. No significant treatment-by-subgroup interaction was observed for the key secondary endpoints between Asian and White patients. In Asian patients, the most common adverse event in the nintedanib group was diarrhoea (56.2% of patients vs 15.6% for placebo). Conclusion: In pre-specified subgroup analyses of Asian versus White patients with IPF in the INPULSIS ® trials, race did not influence the effect of nintedanib on disease progression.

Degradation experiments for AlGaInN-based laser diodes were conducted for the purpose of constructing a possible model of the degradation mechanism. Lasers in this experiment were aged under 30 mW continuous-wave operation at 60 °C, and the lifetime was defined as the time at which the operating current increased by 20%. The lifetime was found to be dependent on the dislocation density of the basal ELOGaN layer, with the degradation rate being almost proportional to the square root of aging time. A model of degradation in which degradation is governed by a diffusion process is proposed based on these results. Although the model describes the experimental findings well, further investigation is considered necessary before the degradation mechanism in AlGaInN lasers can be fully understood.