Determining Optimal Free Dose Combination of Tiotropium Bromide and BI 1744 CL in Chronic Obstructive Pulmonary Disease (COPD)

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Drug: olodaterol (BI 1744) high; Drug: high tiotropium bromide; Drug: olodaterol (BI 1744) low; Drug: low tiotropium bromide; Drug: medium tiotropium bromide; Drug: Placebo; Device: Respimat

Study type: Interventional

Funder types: Industry

Identifiers

NCT01040403

1237.18

2009-014880-38 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this study is to determine the optimum once daily dose of BI 1744 CL and tiotropium in free dose combination (delivered by the Respimat inhaler) after four week treatment in patients with COPD.

Enrollment: 233 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. All patients must sign an informed consent
2. All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) must meet the following spirometric criteria:

a post-bronchodilator forced expiratory flow in 1 second (FEV1) =<30% of predicted normal and <80% of predicted normal and a post bronchodilator FEV1 / forced vital capacity (FVC) <70% at Visit 1 4. Male or female patients, 40 years of age or older. 5. Patients must be current or ex-smokers with a smoking history of more than 10 pack years

Exclusion criteria

• Patients with a significant disease other than COPD;
• Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
• Patients with a history of asthma or a total blood eosinophil count >=600/mm3.
• Patients with any of the following conditions:

a diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists) a diagnosis of paroxysmal tachycardia - Patients with any of the following conditions: a history of myocardial infarction within 1 year of screening visit a diagnosis of clinically relevant cardiac arrhythmia a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years

• Patients who have undergone thoracotomy with pulmonary resection
• Patients being treated with the following concomitant medications:

medications that prolong the QT/QTc interval oral Beta-adrenergics oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day

• Pregnant or nursing women

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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233 participants in 8 patient groups

olodaterol (BI 1744) low and placebo

Experimental group

Description:

low dose inhaled olodaterol orally once daily from the Respimat inhaler

Treatment:

Drug: olodaterol (BI 1744) low

Device: Respimat

Drug: Placebo

olodaterol (BI 1744) low and low tio

Experimental group

Description:

low dose inhaled olodaterol and low dose inhaled tiotropium, both from the Respimat inhaler and once daily

Treatment:

Drug: olodaterol (BI 1744) low

Drug: low tiotropium bromide

Device: Respimat

olodaterol (BI 1744) low and medium tio

Experimental group

Description:

low dose inhaled olodaterol and medium dose inhaled tiotropium, both from the Respimat inhaler and once daily

Treatment:

Drug: olodaterol (BI 1744) low

Drug: medium tiotropium bromide

Device: Respimat

olodaterol (BI 1744) low and high tio

Experimental group

Description:

low dose inhaled olodaterol and high dose inhaled tiotropium, both from the Respimat inhaler and once daily

Treatment:

Drug: olodaterol (BI 1744) low

Drug: high tiotropium bromide

Device: Respimat

olodaterol (BI 1744) high and placebo

Experimental group

Description:

high dose inhaled olodaterol orally once daily from the Respimat inhaler

Treatment:

Drug: olodaterol (BI 1744) high

Device: Respimat

Drug: Placebo

Olodaterol (BI 1744) high and low tio

Experimental group

Description:

high dose inhaled olodaterol and low dose inhaled tiotropium, both from the Respimat inhaler and once daily

Treatment:

Drug: low tiotropium bromide

Drug: olodaterol (BI 1744) high

Device: Respimat

Olodaterol (BI 1744) high and medium tio

Experimental group

Description:

high dose inhaled olodaterol and medium dose inhaled tiotropium, both from the Respimat inhaler and once daily

Treatment:

Drug: medium tiotropium bromide

Drug: olodaterol (BI 1744) high

Device: Respimat

Olodaterol (BI 1744) high and high tio

Experimental group

Description:

high dose inhaled olodaterol and high dose inhaled tiotropium, both from the Respimat inhaler and once daily

Treatment:

Drug: high tiotropium bromide

Drug: olodaterol (BI 1744) high

Device: Respimat