Combining tiotropium with olodaterol significantly improves lung function in COPD patients

Sep 3 2012

New phase II data presented for the first time today at the 2012 European Respiratory Society (ERS) congress show that combining tiotropium with olodaterol significantly improved lung function (FEV₁) over 24 hours in COPD patients compared to olodaterol alone.   

Significant improvements were seen for all combinations of doses tested (tiotropium 1.25, 2.5 and 5 μg / olodaterol 5 μg, 10 μg) compared with the respective olodaterol monotherapies. Both treatments were administered using the patient-preferred Respimat^® Soft Mist^TM Inhaler (SMI) device.

After 4 weeks of treatment, the combination of tiotropium and olodaterol provided an average lung function improvement compared to the pre-treatment baseline of up to 342 mL over the first 6 hours (FEV₁ AUC_0-6) and improvements in trough FEV₁ of up to 166 mL.

Compared to olodaterol monotherapy, the combination of tiotropium and olodaterol further increased lung function by up to 144 mL (FEV₁ AUC_0-6) and 84 mL (trough FEV₁).

The new study completes a comprehensive Phase II programme initiated by Boehringer Ingelheim that thoroughly investigated different doses of each active component to identify the optimal doses for the fixed-dose combination.

Dr. René Aalbers of the Department of Pulmonology, Martini Hospital, Groningen, Netherlands, and lead author of the study said: "Combining two long-acting bronchodilators with different modes of action - the well established once-daily LAMA tiotropium with olodaterol, an investigational and promising once-daily LABA with a convincing 24-hour profile - has a complementary effect in the treatment of COPD patients. Olodaterol is an ideal partner to tiotropium due to its similar long-lasting effect at a low dose."

The new data are from a Phase II dose-finding study: a randomised, double-blind, 4-period, incomplete crossover trial of 4 weeks duration involving 232 COPD patients with post-bronchodilator FEV₁ of ≥30% and <80% of predicted normal.

To assist in the development of the fixed dose combination, various doses of tiotropium (1.25, 2.5 and 5 μg) were tested in combination with either olodaterol 5 μg or 10 μg and efficacy measured against the respective doses of olodaterol as monotherapy.

The study compared pre-dose (trough) lung function and lung function up to 6 hours post-dose after 4 weeks treatment with tiotropium and olodaterol as a free combination versus olodaterol as a monotherapy.

The mono components and all combination doses showed a favourable safety profile.

Comprehensive Phase III programme TOviTO^® ongoing

The TOviTO^® programme, one of the largest global Phase III clinical trial programmes ever conducted in COPD, is already underway to fully evaluate the potential benefits of tiotropium and olodaterol in a once-daily fixed-dose combination using Respimat^® SMI^TM in the treatment of patients with COPD. It consists of several Phase III studies including the two pivotal registration trials TOnado 1&2, which are multi-centred, multi-national, randomised, double-blind, parallel group studies randomising a total of 5,000 COPD patients across the spectrum of disease severity from GOLD Stage II to GOLD Stage IV at more than 500 trial sites in approximately 40 countries.

In addition to evaluating the effects of tiotropium + olodaterol FDC on lung function, the TOviTO^® programme is also focussed on the evaluation of other important clinical outcomes that reflect the daily life of patients with COPD.

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim, said: "Olodaterol, a once-daily LABA with a proven 24-hour profile in patients with COPD, has been designed by Boehringer Ingelheim as an ideal combination partner for tiotropium, the first once-daily inhaled long-acting anticholinergic bronchodilator to provide 24-hour bronchodilation in COPD. These new data give us confidence that we are moving closer to the fixed dose combination product of tiotropium and olodaterol, which could become a new treatment option for patients with COPD."   

Source: Boehringer Ingelheim