Enrollment commences in Boehringer Ingelheim's TOviTO Phase III combination trial for COPD

Boehringer Ingelheim today announced enrollment has commenced in its TOviTO Phase III clinical trial program. It will investigate tiotropium plus olodaterol in a once-daily fixed-dose combination for the treatment of chronic obstructive pulmonary disease (COPD).

A progressive yet treatable disease that restricts patients' lives over time, COPD is estimated to affect over 210 million people worldwide and results in more deaths than breast cancer and diabetes combined.

Tiotropium - marketed under the brand name Spiriva^® in COPD - is a long-acting muscarinic antagonist (LAMA) that provides 24-hour bronchodilation by blocking M₃ muscarinic receptors. Tiotropium is the most prescribed COPD drug worldwide with more than 34 million patient years. Olodaterol is a novel once-daily long-acting β₂-agonist (LABA) that Boehringer Ingelheim has developed as an ideal partner to tiotropium in COPD.

Boehringer Ingelheim has decided to move the once-daily fixed-dose combination of tiotropium plus olodaterol into the TOviTO Phase III trial program on the back of promising olodaterol Phase III trial results, which will be published in the near future. The TOviTO program includes several trials that will provide important evidence to support olodaterol's potential to improve patients' lives beyond optimal bronchodilation. The first two trials to begin in the comprehensive TOviTO program will be TOnado 1 and its replicate study, TOnado 2. TOnado 1 & 2 will be the first two pivotal studies to evaluate the safety and efficacy of the fixed-dose combination for the treatment of COPD patients, and are planned to involve 5000 patients (2500 each) at more than 500 trial sites in approximately 40 countries.

The trials are multi-centered, multi-national, randomised, double-blind, parallel group studies that will compare the efficacy and safety of tiotropium plus olodaterol in fixed-dose combination with that of both mono-compounds (tiotropium and olodaterol). Both the fixed-dose combination and monotherapies will be administered once-daily, for 52 weeks, via Boehringer Ingelheim's Respimat^® Soft Mist™ Inhaler (SMI). Respimat^® SMI is a new generation inhaler that provides a unique slow moving and long-lasting soft mist that is easy to inhale⁶ and produces superior lung deposition. Respimat^® SMI is preferred by patients compared to other currently available inhalers.

Professor Roland Buhl, Head of the Pulmonary Department at the University of Mainz, Germany, and the Co-ordinating investigator for both trials, said: "We hypothesise the combination of tiotropium plus olodaterol, in a single Respimat^® Inhaler device, will provide superior efficacy compared with the once-daily mono compounds. The addition of a LABA to tiotropium, a current COPD standard-of-care, could represent a significant advancement in COPD treatment. For the first time, patients would be able to receive their once-daily dose of tiotropium alongside a specifically selected LABA, all in the one, convenient inhaler."

The trials' primary endpoints will be bronchodilation - as measured by FEV₁ AUC_0-3h response and trough FEV₁ response at 24 weeks - and health status (quality of life) - as measured by the Saint George's Respiratory Questionnaire (SGRQ).

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim, said: "Boehringer Ingelheim is committed to advancing respiratory research and treatment. The development of a true once-daily LABA as a partner to tiotropium underscores the company's commitment to meet the unmet medical needs of COPD patients and improve clinical outcomes. Our goal is to provide patients with a LABA/LAMA fixed-dose combination in a device that was specifically designed with patient benefit and convenience in mind."