| Design | Two replicate 52-week, randomised, double-blind, phase 3 trials |
|---|---|
| Treatment | Nintedanib 150 mg twice daily |
| Control | Placebo |
| Population | 1066 patients with idiopathic pulmonary fibrosis, randomised 3:2 |
| Follow-up | 52 weeks |
| Primary endpoint | Annual rate of decline in forced vital capacity |
| Result | FVC decline -114.7 mL/year with nintedanib versus -239.9 mL/year with placebo in INPULSIS-1 (difference 125.3 mL, 95% CI 77.7 to 172.8, p<0.001), and -113.6 versus -207.3 mL/year in INPULSIS-2 (difference 93.7 mL, 44.8 to 142.7, p<0.001). Time to first acute exacerbation was no different in INPULSIS-1 (HR 1.15) but favoured nintedanib in INPULSIS-2. Diarrhoea was frequent, causing discontinuation in fewer than 5%. |
| Secondary endpoints | Time to first acute exacerbation, St George's Respiratory Questionnaire |
In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, 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.
The trial authors, in the published abstract
The companion to ASCEND, and the drug whose mechanism proved portable: nintedanib went on to work in progressive fibrosing ILD generally (INBUILD) and in scleroderma ILD (SENSCIS). Diarrhoea is the practical limit and the reason dose reduction is routine.
Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014 May 29;370(22):2071-82.