A Study of the Safety and Efficacy of 4 Doses of BI 1744 CL Delivered Via the Respimat in Patients With Asthma.

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Olodaterol (BI 1744) medium; Drug: Olodaterol (BI 1744) low; Drug: Olodaterol (BI 1744) very low; Drug: Placebo; Drug: Formoterol 12 mcg; Drug: Olodaterol (BI 1744) high

Study type: Interventional

Funder types: Industry

Identifiers

NCT01013753

1222.27

2009-013395-48 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this study is to determine the efficacy and safety of 4 doses of BI 1744 CL inhalation solution delivered by the Respimat® inhaler once daily for four weeks in patients with asthma in comparison to placebo.

Enrollment: 198 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. All patients must sign an informed consent consistent with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, i.e. prior to any study procedures which includes medication washout and restrictions. A separate informed consent is required for pharmacogenomic sampling.
2. Male or female patients, aged between 18 and 70 years of age, diurnally active
3. A history of asthma diagnosed by physician at least 3 months prior to Visit 1 at GINA treatment steps 3 or 4. The diagnosis of asthma must have been made before the age of 40.
4. Pre-bronchodilator FEV1 between 60% predicted and 90% predicted at Visit 1.
5. Increase in FEV1 greater or equal to 12% and 200 ml 15 minutes after 400mcg salbutamol (albuterol) at Visit 1.
6. Patient must have been taking inhaled corticosteroids (ICS) for at least 12 weeks prior to screening, and must have been receiving at a stable dose for at least 6 weeks prior to screening either: - a medium to high dose ICS or - a low to high dose ICS in combination with Long acting beta agonist (LABA).
7. All patients must be symptomatic.

Exclusion criteria

1. Patients with a significant disease other than asthma; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient's ability to participate in the study

2. Patients who have been hospitalised for an asthma exacerbation within 3 months or had an admission to an intensive care unit for asthma within 3 years of Visit 1

3. Patients will be excluded when they have: - an aspartate aminotransferase (AST) >80 IU/L, alanine aminotransferase (ALT) >80 IU/L, bilirubin >1.5 X upper limit of normal (ULN) or creatinine >1.5 X ULN - clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis

4. Patients with any of the following conditions: - a diagnosis of thyrotoxicosis

   • a diagnosis of paroxysmal tachycardia (>100 beats per minute)
   • a marked baseline prolongation of QT/QTc interval at Visit 1 (e.g., repeated demonstration of a QTc interval >450 ms) as recommended by ICH E14
   • a history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) as recommended by ICH E14.

5. Patients with any of the following conditions: - a history of myocardial infarction within 1 year of screening visit (Visit 1)

   • a diagnosis of clinically relevant cardiac arrhythmia
   • a history of cor pulmonale
   • known active tuberculosis
   • a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed)
   • a history of life-threatening pulmonary obstruction
   • a history of chronic obstructive pulmonary disease
   • history of cystic fibrosis
   • clinically evident bronchiectasis
   • a history of significant alcohol or drug abuse

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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198 participants in 6 patient groups, including a placebo group

Olodaterol (BI 1744) low

Experimental group

Description:

Low dose inhaled orally once daily from the Respimat inhaler

Treatment:

Drug: Olodaterol (BI 1744) low

Olodaterol (BI 1744) very low

Experimental group

Description:

Very low dose inhaled orally once daily from the Respimat inhaler

Treatment:

Drug: Olodaterol (BI 1744) very low

Olodaterol (BI 1744) medium

Experimental group

Description:

Medium dose inhaled orally once daily from the Respimat inhaler

Treatment:

Drug: Olodaterol (BI 1744) medium

Olodaterol (BI 1744) high

Experimental group

Description:

High dose inhaled orally once daily from the Respimat inhaler

Treatment:

Drug: Olodaterol (BI 1744) high

Formoterol 12 mcg

Active Comparator group

Description:

12mcg inhaled twice daily from the Aerolizer inhaler

Treatment:

Drug: Formoterol 12 mcg

Placebo

Placebo Comparator group

Description:

Olodaterol (BI 1744) placebo inhaled once daily from the Respimat inhaler and/or Formoterol placebo inhaled twice daily from the Aerolizer inhaler

Treatment:

Drug: Placebo