Boehringer Ingelheim presented today for the first time data from a Phase II dose ranging study investigationg the combination of olodaterol, an investigational long-acting beta2-agonist (LABA), and tiotropium, a long-acting muscarinic antagonist (LAMA), in COPD patients, compared to the investigational agent olodaterol alone. The data were presented at the 2012 European Respiratory Society (ERS) Congress in Vienna, Austria. The new study completes a comprehensive Phase II program initiated by Boehringer Ingelheim to thoroughly investigate different doses of each active component to identify the appropriate doses for the fixed-dose combination.
The Phase II dose-finding study is a randomized, 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 microgram) were tested in combination with either olodaterol 5 microgram or 10 microgram and efficacy was measured against the respective doses of olodaterol as monotherapy. Both treatments were delivered via the Respimat® inhaler.
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. Significant improvements were seen for all combinations of doses tested (tiotropium 1.25, 2.5 and 5 microgram / olodaterol 5 microgram, 10 microgram) compared with the respective olodaterol monotherapies.
After 4 weeks of treatment, the free combination of tiotropium and olodaterol provided an average lung function improvement of up to 342 mL over the first 6 hours (FEV1 AUC0-6) compared to pre-dose lung function mean baseline values and improvements in trough FEV1 of up to 166 mL, compared to pre-treatment FEV1 mean baseline values.
No safety or tolerability concerns were identified beyond what is known for the components. Treatment with both olodaterol monotherapy and combinations of tiotropium/olodaterol once daily was generally well tolerated within this small study population. Adverse events seen in greater than 5% of patients in any treatment group were nasopharyngitis and COPD.
"Boehringer Ingelheim conducted a comprehensive Phase II program investigating different doses of each active component to identify the optimal doses for the combination," said Tunde Otulana, MD, Vice President, Clinical Development and Medical Affairs, Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc. "We are committed to the clinical development program of olodaterol and the combination with tiotropium in order to identify new treatment options for patients with COPD."
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