ABSTRACT
The 3-min constant speed shuttle test (CSST) was used to examine the effect of tiotropium/olodaterol compared with tiotropium at reducing activity-related breathlessness in patients with chronic obstructive pulmonary disease (COPD).This was a randomised, double-blind, two-period crossover study including COPD patients with moderate to severe pulmonary impairment, lung hyperinflation at rest and a Mahler Baseline Dyspnoea Index <8. Patients received 6â weeks of tiotropium/olodaterol 5/5â µg and tiotropium 5â µg in a randomised order with a 3-week washout period. The speed for the 3-min CSST was determined for each patient such that an intensity of breathing discomfort ≥4 ("somewhat severe") on the modified Borg scale was reached at the end of a completed 3-min CSST.After 6â weeks, there was a decrease in the intensity of breathlessness (Borg dyspnoea score) at the end of the 3-min CSST from baseline with both tiotropium (mean -0.968, 95% CI -1.238-â-0.698; n=100) and tiotropium/olodaterol (mean -1.325, 95% CI -1.594-â-1.056; n=101). The decrease in breathlessness was statistically significantly greater with tiotropium/olodaterol versus tiotropium (treatment difference -0.357, 95% CI -0.661-â-0.053; p=0.0217).Tiotropium/olodaterol reduced activity-related breathlessness more than tiotropium in dyspnoeic patients with moderate to severe COPD exhibiting lung hyperinflation.
Subject(s)
Benzoxazines/administration & dosage , Bronchodilator Agents/administration & dosage , Dyspnea/drug therapy , Lung/drug effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Tiotropium Bromide/administration & dosage , Administration, Inhalation , Aged , Benzoxazines/adverse effects , Bronchodilator Agents/adverse effects , Cross-Over Studies , Double-Blind Method , Drug Combinations , Dyspnea/etiology , Exercise Test , Exercise Tolerance , Female , Forced Expiratory Volume , Humans , Internationality , Lung/physiopathology , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Recovery of Function , Severity of Illness Index , Time Factors , Tiotropium Bromide/adverse effects , Treatment Outcome , Vital CapacityABSTRACT
BACKGROUND: This randomised, double-blind, four-way, crossover, Phase II study compared the 24-h forced expiratory volume in 1 s (FEV1) profile of alternative dosing frequencies of two total daily doses of olodaterol (5 and 10 µg) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients received olodaterol 2 µg twice daily (BID), 5 µg BID, 5 µg once daily (QD) and 10 µg QD in a randomised sequence over 3-week treatment periods. Co-primary end points were FEV1 area under the curve from 0 to 12 h (AUC0-12) and area under the curve from 12 to 24 h (AUC12-24) responses. Additional lung-function responses, pharmacokinetics and safety were assessed. RESULTS: 47 patients were treated. All olodaterol doses provided significant increases in FEV1 versus baseline (p < 0.001) and FEV1 time profiles were nearly identical for olodaterol 5 and 10 µg QD. Olodaterol 5 µg QD demonstrated improved FEV1 AUC0-12 and similar AUC12-24 versus 2 µg BID. Olodaterol 5 µg QD showed slightly increased FEV1 AUC0-12 but lower AUC12-24 compared to 5 µg BID. Bronchodilation over 24 h was similar for olodaterol 5 µg QD and BID. All doses were well tolerated. CONCLUSIONS: Olodaterol 5 µg QD is efficacious in COPD, with a superior bronchodilatory profile compared to 2 µg BID, which is close to the same total daily dose, and a similar degree of bronchodilation over 24 h compared with double the daily dose (administered as 10 µg QD or 5 µg BID). TRIAL REGISTRATION: ClinicalTrials.gov: NCT00846768.
