PURPOSE: The β2-adrenergic receptor agonists and anticholinergics are two distinct classes of bronchodilators that have different therapeutic effects in patients with chronic obstructive pulmonary disease (COPD). We report results from a clinical trial designed to investigate whether the therapeutic effect associated with treatment with formoterol (FORM) plus tiotropium (TIO) was greater than the effect of treatment with TIO alone in patients with COPD.
METHODS: 12-week, randomized, placebo-controlled, double-blind, parallel-group, multicenter study in COPD patients aged ≥40 years who were current or ex-smokers. Patients received FORM 12μg BID and TIO 18μg QD or TIO 18μg QD and placebo. The primary efficacy endpoint was the change from baseline in the normalized area under the curve (AUC) for FEV1 measured 0 to 4 hours postmorning dose (FEV1 AUC 0–4h) at the last visit. Secondary efficacy endpoints included comparisons of trough effects on FEV1 and FVC (average of values 10 and 30 minutes predose) and onset of effects on FEV1 following the first dose.
RESULTS: FORM+TIO (n=116) significantly increased the normalized FEV1 AUC 0-4h compared with TIO (n=124) at all time points postbaseline, with mean treatment differences that reached clinical significance (>100mL change). Mean treatment differences (95% CI) at weeks 4, 8, and 12, and endpoint were 150mL (90, 220), 170mL (100, 230), 180mL (120, 240), and 170mL (120, 230), respectively (all P<0.001). At endpoint, increases from baseline in trough FEV1 and FVC were significantly greater with FORM+TIO (n=121) than with TIO (n=129), with mean treatment differences of 80mL and 160mL, respectively (both P=0.004). The increase in FEV1 5 minutes postdose was significantly greater with FORM+TIO than with TIO (180mL vs 40mL, respectively; P<0.001). Both treatments were similarly well tolerated.
CONCLUSION: The therapeutic effect of treatment with FORM+TIO was greater than the effect of treatment with TIO alone in COPD patients. Significant differences between treatments were observed as early as 5 minutes postdose (the first scheduled measurement).
CLINICAL IMPLICATIONS: The effect of FORM+TIO was greater than the effect of TIO alone in COPD patients.
DISCLOSURE: Donald Tashkin, No Product/Research Disclosure Information; Grant monies (from industry related sources) Dr. Tashkin has received industry-sponsored grants from Schering-Plough; Consultant fee, speaker bureau, advisory committee, etc. Dr. Tashkin has received honoraria for advisory boards and speaking engagements from Schering-Plough.