Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis: Results of two 52-week, Phase III, randomized, placebo-controlled trials (INPULSIS™)
Background: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases.
Methods: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 [NCT01335464] and INPULSIS-2 [NCT01335477]) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis (IPF). The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period.
Results: A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was –114.7 ml with nintedanib versus –239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; p < 0.001) in INPULSIS-1 and –113.6 ml with nintedanib versus –207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; p < 0.001) in INPULSIS-2. In INPULSIS-2, there was a significant benefit with nintedanib in the time to the first acute exacerbation versus placebo (hazard ratio (HR), 0.38; 95% CI, 0.19 to 0.77; P= 0.005); in INPULSIS-1, no significant difference was found (HR, 1.15; 95% CI, 0.54 to 2.42; P= 0.67); The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% (nintedanib vs. placebo) in INPULSIS-1 as well as 63.2% and 18.3% in INPULSIS-2, respectively.
Conclusions: In patients with IPF, nintedanib significantly reduced the decline in FVC by approximately 50%, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients.
Presented at ATS 2014