A study has investigated the effects on 24-h lung function and lung volume of a once-daily fixed-dose combination ( FDC ) of the long-acting muscarinic antagonist Tiotropium and the long-acting beta2-agonist Olodaterol in patients with chronic obstructive pulmonary disease.
This was a randomised, double-blind, placebo-controlled, phase III trial with an incomplete crossover design. Patients received four of the following six treatment options for 6 weeks each: placebo, Olodaterol 5 mcg, Tiotropium 2.5 mcg, Tiotropium 5 mcg, Tiotropium plus Olodaterol FDC 2.5/5 mcg and Tiotropium plus Olodaterol FDC 5/5 mcg, all delivered via the Respimat inhaler.
The primary end point was forced expiratory volume in 1 s ( FEV1 ) area under the curve from 0 to 24 h ( AUC0-24 ) response after 6 weeks of treatment; key secondary end points were FEV1 AUC from 0 to 12 h and AUC from 12 to 24 h, and further end points included lung-volume parameters measured using body plethysmography ( subset of patients ), measures of peak and trough FEV1, and incidence of adverse events.
A significant improvement in FEV1 AUC0-24 response was observed with Tiotropium plus Olodaterol 5/5 mcg and 2.5/5 mcg versus placebo and monotherapies after 6 weeks of treatment; mean response with Tiotropium plus Olodaterol 5/5 mcg versus placebo was 0.280 L ( p less than 0.0001 ).
Differences to monotherapies with Tiotropium plus Olodaterol 5/5 mcg were 0.115 L versus Olodaterol 5 mcg, 0.127 L versus Tiotropium 2.5 mcg and 0.110 L versus Tiotropium 5 mcg ( p less than 0.0001 for all comparisons ).
Secondary end points supported these data.
No safety concerns were identified.
In conclusion, overall, this study has demonstrated improvements in lung function over 24 h with an FDC of Tiotropium plus Olodaterol over Tiotropium or Olodaterol alone, with no observed difference in tolerability. ( Xagena )
Beeh KM et al, Pulm Pharmacol Ther 2015;32:53-59