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

NCT01013753 | Completed Phase 2 Results

• 2 other identifiers: 1222.272009-013395-48
• Study Type: interventional
• Target: 198
• Locations: 5 countries
• Sites: 23

Brief Summary

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period

  Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.

  1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks

Secondary Outcomes (30)

• FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response at the End of Each Treatment Period

  1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks

• FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response at the End of Each Treatment Period

  1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks

• Peak FEV1 Within 24 Hours Post-dose Response

  1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks

• Trough FEV1 Response

  1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening dose after 4 weeks

• Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response

  1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h , 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks

Study Arms (6)

Olodaterol (BI 1744) low

EXPERIMENTAL

Low dose inhaled orally once daily from the Respimat inhaler

Drug: Olodaterol (BI 1744) low

Olodaterol (BI 1744) very low

EXPERIMENTAL

Very low dose inhaled orally once daily from the Respimat inhaler

Drug: Olodaterol (BI 1744) very low

Olodaterol (BI 1744) medium

EXPERIMENTAL

Medium dose inhaled orally once daily from the Respimat inhaler

Drug: Olodaterol (BI 1744) medium

Olodaterol (BI 1744) high

EXPERIMENTAL

High dose inhaled orally once daily from the Respimat inhaler

Drug: Olodaterol (BI 1744) high

Formoterol 12 mcg

ACTIVE COMPARATOR

12mcg inhaled twice daily from the Aerolizer inhaler

Drug: Formoterol 12 mcg

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo DRUG

Determine efficacy and safety of Placebo inhaled once daily from the Respimat inhaler and/or twice daily from the Aerolizer inhaler

Placebo

Olodaterol (BI 1744) high DRUG

Determine efficacy and safety in 4 different doses of Olodaterol (BI 1744) inhaled once daily via the Respimat

Olodaterol (BI 1744) high

Olodaterol (BI 1744) medium DRUG

Determination of efficacy in 4 different doses of Olodaterol (BI 1744) inhaled once daily via the Respimat

Olodaterol (BI 1744) medium

Olodaterol (BI 1744) very low DRUG

Determination of efficacy in 4 different doses of Olodaterol (BI 1744) inhaled once daily via the Respimat

Olodaterol (BI 1744) very low

Formoterol 12 mcg DRUG

Determine efficacy and safety of 12 mcg Formoterol dose inhaled orally twice daily from the Aerolizer in comparison to other treatment groups

Formoterol 12 mcg

Olodaterol (BI 1744) low DRUG

Determine efficacy and safety of 4 different doses of Olodaterol (BI 1744) inhaled once daily via the Respimat

Olodaterol (BI 1744) low

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female patients, aged between 18 and 70 years of age, diurnally active
• 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.
• Pre-bronchodilator FEV1 between 60% predicted and 90% predicted at Visit 1.
• Increase in FEV1 greater or equal to 12% and 200 ml 15 minutes after 400mcg salbutamol (albuterol) at Visit 1.
• 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).
• All patients must be symptomatic.

You may not qualify if:

• 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
• 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
• 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
• 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.
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (27)

1222.27.43002 Boehringer Ingelheim Investigational Site

Linz, Austria

Location

1222.27.43004 Boehringer Ingelheim Investigational Site

Schlüsslberg, Austria

Location

1222.27.43001 Boehringer Ingelheim Investigational Site

Thalheim bei Wels, Austria

Location

1222.27.43003 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

1222.27.49003 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1222.27.49004 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1222.27.49009 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1222.27.49011 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

1222.27.49008 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1222.27.49002 Boehringer Ingelheim Investigational Site

Lübeck, Germany

Location

1222.27.49007 Boehringer Ingelheim Investigational Site

Rüdersdorf, Germany

Location

1222.27.49006 Boehringer Ingelheim Investigational Site

Wiesbaden, Germany

Location

1222.27.49010 Boehringer Ingelheim Investigational Site

Wiesloch, Germany

Location

1222.27.48001 Boehringer Ingelheim Investigational Site

Lodz, Poland

Location

1222.27.48002 Boehringer Ingelheim Investigational Site

Lodz, Poland

Location

1222.27.48003 Boehringer Ingelheim Investigational Site

Poznan, Poland

Location

1222.27.48004 Boehringer Ingelheim Investigational Site

Proszowice, Poland

Location

1222.27.40002 Boehringer Ingelheim Investigational Site

Bucharest, Romania

Location

1222.27.40003 Boehringer Ingelheim Investigational Site

Bucharest, Romania

Location

1222.27.42101 Boehringer Ingelheim Investigational Site

Bardejov, Slovakia

Location

1222.27.42103 Boehringer Ingelheim Investigational Site

Lučenec, Slovakia

Location

1222.27.42104 Boehringer Ingelheim Investigational Site

Martin, Slovakia

Location

1222.27.42102 Boehringer Ingelheim Investigational Site

Spišská Nová Ves, Slovakia

Location

1222.27.38601 Boehringer Ingelheim Investigational Site

Golnik, Slovenia

Location

1222.27.38605 Boehringer Ingelheim Investigational Site

Kamnik, Slovenia

Location

1222.27.38604 Boehringer Ingelheim Investigational Site

Topolšica, Slovenia

Location

1222.27.38603 Boehringer Ingelheim Investigational Site

Zgornje Hoče, Slovenia

Location

Related Publications (1)

• O'Byrne PM, D'Urzo T, Beck E, Flezar M, Gahlemann M, Hart L, Blahova Z, Toorawa R, Beeh KM. Dose-finding evaluation of once-daily treatment with olodaterol, a novel long-acting beta2-agonist, in patients with asthma: results of a parallel-group study and a crossover study. Respir Res. 2015 Aug 18;16(1):97. doi: 10.1186/s12931-015-0249-8.

  PMID: 26283085 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

olodaterol; Culture Media; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Laboratory Chemicals; Specialty Uses of Chemicals; Chemical Actions and Uses; Equipment and Supplies; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2009
• First Posted: November 16, 2009
• Study Start: February 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: June 27, 2014
• Results First Posted: June 5, 2014

Record last verified: 2014-05

Locations

RO (2); DE (9); SL (4); PL (4); AU (4)