Spiriva Respimat Soft Mist tiotropium: Phase III data

Data from the pair of identical double-blind, international Phase III PrimoTinA-asthma trials in 912 patients with severe persistent asthma showed that 5 µg twice-daily tiotropium as add-on therapy to usual care met the co-primary endpoints of mean change in peak and trough FEV1 from baseline to week 24 vs. placebo plus usual care. In the first trial in 459 patients, tiotropium improved peak FEV1 by 86 mL and trough FEV1 by 88 mL at week 24 from baseline compared to placebo (p=0.01 for both). In the second trial in 453 patients, tiotropium improved peak FEV1 by 154 mL and trough FEV1 by 111 mL at week 24 from baseline compared to placebo (p<0.001 for both). On a third co-primary endpoint that was measured using 48-week pooled data from both trials, tiotropium significantly increased the time to first severe exacerbation defined as deterioration of asthma necessitating initiation or doubling of systemic glucocorticoids for >=3 days vs. placebo, (282 vs. 226 days, respectively; p=0.03). Boehringer said that since <50% of patients had a severe exacerbation, median time to the first severe exacerbation could not be calculated. On secondary endpoints in the first trial, tiotropium improved peak FVC by 89 mL and trough FVC by 136 mL at week 24. Tiotropium also improved PEF by 21.5 L/min in the morning and by 22 L/min in the evening at week 24. On secondary endpoints in the second trial, tiotropium improved peak FVC by 94 mL and trough FVC by 106 mL at week 24. Tiotropium also improved peak PEF by 23.3 L/min in the morning and by 29.9 L/min in the evening at week 24. Pooled safety data from 2 trials showed that serious adverse events were reported in 8.1% of patients receiving tiotropium and 8.8% of patients receiving placebo. Asthma exacerbations occurred in 2 patients and 1 patient was admitted to the hospital for cerebral infarction. There were no deaths in either trial. The most common adverse events were nasopharyngitis and headache. Usual care included high-dose inhaled glucocorticoids and long acting beta 2 agonists (LABAs). Data were published in the New England Journal of Medicine and presented at the European Respiratory Society meeting in Vienna. ...