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 MistTM 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
AUC0-6) 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
AUC0-6) 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
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
Comprehensive Phase III programme TOviTO®
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® SMITM
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
Source: Boehringer Ingelheim