Once versus twice daily formoterol via Novolizer ® for patients with moderate to severe COPD—A double-blind, randomised, controlled trial

Abstract

Study objectives To evaluate in patients with moderate to severe COPD whether a single morning dose of 24 μg formoterol from the Novolizer ® is not inferior to two divided doses of 12 μg formoterol inhaled in the morning and in the evening. Design Randomised, double blind, active-controlled, parallel-group, multi-centre study with a 2-week run-in period and a 12-week treatment phase. Setting Forty-seven outpatient centres in Germany, including private practices. Participants N = 321 symptomatic patients with moderate to severe COPD aged 40–70 years with an FEV 1 of 30–80% predicted and the requirement of 3–12 actuations of salbutamol per day on ⩾5 days during the run-in period. Treatment Eligible patients were randomised to inhale formoterol either (a) as a single 24 μg dose in the morning (OD) or (b) in two divided 12 μg doses in the morning and in the evening (b.i.d.). Measurements and results The mean age was 60.3 (SD 7.3) years, and mean baseline pre-dose FEV 1 was 1.5 l (0.5 l) or 50% (12%) of predicted, respectively. After 12 weeks of treatment, pre-dose FEV 1 improved in both groups (mean: OD, +104 ml, b.i.d., +135 ml, mean difference between groups: 31 ml). The 95% CI exceeded the pre-determined margin of 100 ml by 2 ml, so that the statistical hypothesis of non-inferiority of once daily dosing was not confirmed. No statistically significant differences were seen for improvements in PEF, MEF 75, MEF 50, and MEF 25. COPD symptoms, percentage of symptom-free days and quality of life (SGRQ) improved in both groups to a similar degree. There were no relevant differences in the incidence of adverse events. Conclusions Based on a comparable efficacy and tolerability, the dosing schedule with formoterol via Novolizer ® as once daily in the morning seems to be an alternative compared to twice daily treatment. The primary endpoint suggests the equivalence of both treatment schedules from a clinical perspective. This regimen can be considered as an alternative therapeutic approach for a subgroup of COPD patients and may help to improve patient compliance.