Clinical trial NCT01013753: A Study of the Safety and Efficacy of 4 Doses of BI 1744 CL Delivered Via the Respimat in Patients With Asthma.
Official title: A Randomised, Double-Blind, Placebo- and Active-Controlled, Incomplete Crossover Efficacy and Safety Comparison of 4-week Treatment Periods of Once Daily Treatment of 4 Doses of BI 1744 CL Inhalation Solution Delivered by the Respimat® in Patients With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-11-16
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period
timeFrame: 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:
measure: FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response at the End of Each Treatment Period
timeFrame: 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
measure: FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response at the End of Each Treatment Period
timeFrame: 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
measure: Peak FEV1 Within 24 Hours Post-dose Response
timeFrame: 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
measure: Trough FEV1 Response
timeFrame: 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
measure: Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
timeFrame: 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
measure: FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
timeFrame: 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
measure: FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
timeFrame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 min, 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
measure: Peak FVC Within 24 Hours Post-dose Response
timeFrame: 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
measure: Trough FVC Response
timeFrame: 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
measure: Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response
timeFrame: 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
measure: PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response
timeFrame: 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
measure: Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response
timeFrame: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1h, -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
measure: Peak PEF Within 24 Hours Post-dose Response
timeFrame: 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
measure: Trough PEF Response
timeFrame: 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
measure: Mean Pre-dose Morning PEF (PEF a.m.)
timeFrame: 2-4 weeks
measure: Mean Pre-dose Evening PEF (PEF p.m.)
timeFrame: 2-4 weeks
measure: PEF Daily Variability
timeFrame: 2-4 weeks
measure: Mean Pre-dose Morning FEV1 (FEV1 a.m.)
timeFrame: 2-4 weeks
measure: Mean Pre-dose Evening FEV1 (FEV1 p.m.)
timeFrame: 2-4 weeks
measure: Mean Number of Puffs of Rescue Medication During the Whole Day
timeFrame: 2-4 weeks
measure: Percentage of Asthma Symptom Free Days
timeFrame: 2-4 weeks
measure: Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
timeFrame: 2-4 weeks
measure: Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
timeFrame: 2-4 weeks
measure: Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
timeFrame: 2-4 weeks
measure: Total Asthma Quality of Life Questionnaire (AQLQ(s)) Score
timeFrame: 4 weeks
measure: Total Asthma Control Questionnaire (ACQ) Score
timeFrame: 4 weeks
measure: Potassium 1 Hour Pre-dose
timeFrame: 4 weeks
measure: Potassium 1 Hour Post-dose
timeFrame: 4 weeks
measure: Potassium 3 Hours Post-dose
timeFrame: 4 weeks
measure: Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Linz
country: Austria
facility: 1222.27.43002 Boehringer Ingelheim Investigational Site
city: Schlüsslberg
country: Austria
facility: 1222.27.43004 Boehringer Ingelheim Investigational Site
city: Thalheim bei Wels
country: Austria
facility: 1222.27.43001 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1222.27.43003 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.27.49003 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.27.49004 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.27.49009 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1222.27.49011 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1222.27.49008 Boehringer Ingelheim Investigational Site
city: Lübeck
country: Germany
facility: 1222.27.49002 Boehringer Ingelheim Investigational Site
city: Rüdersdorf
country: Germany
facility: 1222.27.49007 Boehringer Ingelheim Investigational Site
city: Wiesbaden
country: Germany
facility: 1222.27.49006 Boehringer Ingelheim Investigational Site
city: Wiesloch
country: Germany
facility: 1222.27.49010 Boehringer Ingelheim Investigational Site
city: Lodz
country: Poland
facility: 1222.27.48001 Boehringer Ingelheim Investigational Site
city: Lodz
country: Poland
facility: 1222.27.48002 Boehringer Ingelheim Investigational Site
city: Poznan
country: Poland
facility: 1222.27.48003 Boehringer Ingelheim Investigational Site
city: Proszowice
country: Poland
facility: 1222.27.48004 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1222.27.40002 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1222.27.40003 Boehringer Ingelheim Investigational Site
city: Bardejov
country: Slovakia
facility: 1222.27.42101 Boehringer Ingelheim Investigational Site
city: Lucenec
country: Slovakia
facility: 1222.27.42103 Boehringer Ingelheim Investigational Site
city: Martin
country: Slovakia
facility: 1222.27.42104 Boehringer Ingelheim Investigational Site
city: Spisska Nova Ves
country: Slovakia
facility: 1222.27.42102 Boehringer Ingelheim Investigational Site
city: Golnik
country: Slovenia
facility: 1222.27.38601 Boehringer Ingelheim Investigational Site
city: Hoce
country: Slovenia
facility: 1222.27.38603 Boehringer Ingelheim Investigational Site
city: Kamnik
country: Slovenia
facility: 1222.27.38605 Boehringer Ingelheim Investigational Site
city: Topolsica
country: Slovenia
facility: 1222.27.38604 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.