Study objectives: To evaluate in patients with moderate to severe COPD whether a single morning dose of 24 microg formoterol from the Novolizer is not inferior to two divided doses of 12 microg 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 FEV1 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 microg dose in the morning (OD) or (b) in two divided 12 microg 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 FEV1 was 1.5l (0.5l) 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 100ml 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, MEF75, MEF50, and MEF25. 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.