Introduction Period 1 of the TOMORROW trial was a phase II, randomised, placebo-controlled trial of four doses of nintedanib (50 mg qd, 50 mg bid, 100 mg bid, 150 mg bid) in patients with idiopathic pulmonary fibrosis (IPF) over 52 weeks. Results suggested that nintedanib 150 mg bid was associated with a reduced decline in forced vital capacity (FVC) and fewer acute exacerbations versus placebo. After completing period 1, patients could continue treatment in a further blinded treatment phase (period 2).
Methods In period 2, patients treated with nintedanib in period 1 continued their dose, and placebo-treated patients switched to nintedanib 50 mg qd. Here we present descriptive data on FVC, acute exacerbations, mortality and adverse events for the nintedanib 150 mg bid and comparator (placebo/nintedanib 50 mg qd) groups during periods 1 and 2.
Results Of 428 patients treated in period 1 (nintedanib 150 mg bid n = 85, placebo n = 85), 316 patients completed period 1 and 286 patients (nintedanib 150 mg bid n = 48, comparator n = 54) continued treatment in period 2. Mean total duration of exposure was 14.2 months for nintedanib 150 mg bid and 16.8 months for comparator. The mean observed change from baseline in FVC over time was consistently lower in the nintedanib 150 mg bid group compared with comparator across periods 1 and 2 (Figure 1). The incidence of acute exacerbations was lower in the nintedanib 150 mg bid group compared with comparator (3.2 vs. 13.4 per 100 patient-years). Overall, 14 patients (16.3%) died in the nintedanib 150 mg bid group and 19 patients (21.8%) died in the comparator group. The safety and tolerability of nintedanib 150 mg bid was similar between periods 1 and 2. The proportion of patients reporting an adverse event across periods 1 and 2 was similar in the nintedanib 150 mg bid and comparator groups (97.6% and 94.1%, respectively).
Conclusion In the TOMORROW trial, the effect of nintedanib on slowing disease progression in patients with IPF was maintained up to week 76. No relevant changes in the safety and tolerability of nintedanib were observed with treatment up to week 76 compared with week 52.