A Study to Compare the Efficacy and Safety of Different Dosings of Olodaterol Administered With the Respimat® Inhaler in Patients With Moderate to Severe Asthma

Asthma Clinical Trial

Official title:

Phase II, Randomised, Double-Blind, Cross-over Study to Compare the 24-hour FEV1-time Profile of Orally Inhaled Olodaterol, Delivered With the Respimat® Inhaler, After 3 Weeks of Olodaterol Once Daily Medium Dose, Twice Daily Low Dose and Placebo or After 3 Weeks of Once Daily High Dose, Twice Daily Medium Dose and Placebo Administration in Patients With Moderate to Severe Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01311661
• Other study ID #: 1222.29
• Secondary ID: 2008-006625-14
• Status: Completed
• Phase: Phase 2
• First received: March 4, 2011
• Last updated: March 28, 2014
• Start date: March 2011

Study information

• Verified date: March 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacySlovakia: State Institute for Drug ControlSlovenia: Agency for Medicinal Products - Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will compare efficacy and safety of different regimens of olodaterol administration in asthma (once daily, twice daily) with placebo in a complete cross-over design each within one of the two daily dose groups (medium or high daily dose).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria:

1. Patients of either sex.

2. Aged 18 to 70 years.

3. A current diagnosis and a documented minimum 3 month history of asthma Global Initiative for Asthma (GINA) treatment steps 3 and 4.

4. Prebronchodilator Forced Expiratory Volume in one second (FEV1) >= 60% predicted and < 90% predicted according to European Coal and Steel Community (ECSC).

5. Increase in FEV1 >=12% and >=200 mL 15 min. after 400 µg salbutamol (albuterol);

6. Stable on medium to high dose inhaled corticosteroids (ICS) or low to high dose ICS in combination with a long acting beta-adrenergics (LABA) for at least 6 weeks prior to screening. Stable on ICS mono component of the former fixed LABA/ICS treatment for at least 48 hours prior to Visit 1b.

Exclusion criteria:

1. Patients with a significant disease other than asthma.

2. History of frequent seasonal exacerbations of asthma (defined as one or more seasonal exacerbations every year for the past three years).

3. Upper respiratory tract infection in the past 3 weeks prior to screening visit 1b.

4. Oral or other systemic corticosteroids in the past 6 weeks.

5. Patients with allergen desensitization therapy if started within two years, if they are not on an established maintenance regimen characterized by dose adjustments but no further increase to the tolerable maximum in the same course of immunotherapy.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Placebo twice daily
Inhaled Placebo of Olodaterol twice daily
• Olodaterol low daily dose twice daily
Inhaled Olodaterol medium daily dose administered as low dose twice daily
• Olodaterol medium daily dose twice daily
Inhaled Olodaterol high daily dose administered as medium dose twice daily
• Placebo twice daily
Inhaled Placebo of Olodaterol twice daily
• Olodaterol high daily dose once daily and placebo
Inhaled Olodaterol high daily dose administered as one full dose once daily and placebo once daily
• Olodaterol medium daily dose once daily and placebo
Inhaled Olodaterol medium daily dose administered as one full dose once daily and placebo once daily

Locations

Country	Name	City	State
Austria	1222.29.43003 Boehringer Ingelheim Investigational Site	Linz
Austria	1222.29.43002 Boehringer Ingelheim Investigational Site	Schlüsslberg
Austria	1222.29.43001 Boehringer Ingelheim Investigational Site	Thalheim bei Wels
Austria	1222.29.43004 Boehringer Ingelheim Investigational Site	Wels
Germany	1222.29.49004 Boehringer Ingelheim Investigational Site	Berlin
Germany	1222.29.49006 Boehringer Ingelheim Investigational Site	Berlin
Germany	1222.29.49007 Boehringer Ingelheim Investigational Site	Berlin
Germany	1222.29.49008 Boehringer Ingelheim Investigational Site	Berlin
Germany	1222.29.49002 Boehringer Ingelheim Investigational Site	Frankfurt
Germany	1222.29.49010 Boehringer Ingelheim Investigational Site	Großhansdorf
Germany	1222.29.49003 Boehringer Ingelheim Investigational Site	Lübeck
Germany	1222.29.49005 Boehringer Ingelheim Investigational Site	Rüdersdorf
Germany	1222.29.49001 Boehringer Ingelheim Investigational Site	Wiesbaden
Germany	1222.29.49009 Boehringer Ingelheim Investigational Site	Wiesloch
Hungary	1222.29.36002 Boehringer Ingelheim Investigational Site	Mosonmagyarovar
Hungary	1222.29.36003 Boehringer Ingelheim Investigational Site	Nyiregyhaza
Hungary	1222.29.36001 Boehringer Ingelheim Investigational Site	Sopron
Hungary	1222.29.36004 Boehringer Ingelheim Investigational Site	Zalaegerszeg
Slovakia	1222.29.42001 Boehringer Ingelheim Investigational Site	Bardejov
Slovakia	1222.29.42002 Boehringer Ingelheim Investigational Site	Martin
Slovakia	1222.29.42004 Boehringer Ingelheim Investigational Site	Nitra
Slovakia	1222.29.42003 Boehringer Ingelheim Investigational Site	Spisska Nova Ves
Slovenia	1222.29.38003 Boehringer Ingelheim Investigational Site	Golnik
Slovenia	1222.29.38002 Boehringer Ingelheim Investigational Site	Kamnik
United States	1222.29.11008 Boehringer Ingelheim Investigational Site	Canton	Ohio
United States	1222.29.11001 Boehringer Ingelheim Investigational Site	Centennial	Colorado
United States	1222.29.11007 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio
United States	1222.29.11006 Boehringer Ingelheim Investigational Site	Huntington Beach	California
United States	1222.29.11004 Boehringer Ingelheim Investigational Site	North Dartmouth	Massachusetts
United States	1222.29.11002 Boehringer Ingelheim Investigational Site	Overland Park	Kansas
United States	1222.29.11003 Boehringer Ingelheim Investigational Site	Raleigh	North Carolina
United States	1222.29.11010 Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	1222.29.11009 Boehringer Ingelheim Investigational Site	Skillman	New Jersey
United States	1222.29.11005 Boehringer Ingelheim Investigational Site	Spartanburg	South Carolina
United States	1222.29.11011 Boehringer Ingelheim Investigational Site	St. Louis	Missouri
United States	1222.29.11012 Boehringer Ingelheim Investigational Site	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Austria,  Germany,  Hungary,  Slovakia,  Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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, 6 h, 8 h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) 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 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) 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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks	No
Secondary	FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) 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 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.	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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Peak FEV1 Within 24 Hours Post-dose Response	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. Peak FEV1 within 24 hours post dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.	1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Trough FEV1 Response	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. Trough values were defined as the mean of 2 FEV1 values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.	1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time 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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks	No
Secondary	FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.	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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time 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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Peak FVC Within 24 Hours Post-dose Response	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC within 24 hours post-dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.	1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Trough FVC Response	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were defined as the mean of 2 FVC values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.	1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response	Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.	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, 6 h, 8h, 10 h, 11 h 50 min related to morning dose after 3 weeks	No
Secondary	PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response	Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.	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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response	Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.	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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Peak PEF Within 24 Hours Post-dose Response	Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Peak PEF within 24 hours post dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.	1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Trough PEF Response	Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Trough values were defined as the mean of 2 PEF values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.	1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks	No
Secondary	Mean Pre-dose Morning PEF (PEF a.m.)	PEF a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.	0-3 weeks	No
Secondary	Mean Pre-dose Evening PEF (PEF p.m.)	PEF p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.	0-3 weeks	No
Secondary	PEF Daily Variability	PEF daily variability was assessed by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). PEF daily variability is the absolute difference between the morning and the evening PEF value divided by the mean of these two values, expressed as a percent. Means are adjusted for treatment, period, patient and study baseline.	0-3 weeks	No
Secondary	Mean Pre-dose Morning FEV1 (FEV1 a.m.)	FEV1 a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.	0-3 weeks	No
Secondary	Mean Pre-dose Evening FEV1 (FEV1 p.m.)	FEV1 p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.	0-3 weeks	No
Secondary	Mean Number of Puffs of Rescue Medication During the Whole Day	Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM3 device (overall mean number obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.	0-3 weeks	No
Secondary	Percentage of Asthma Symptom Free Days	Percentage of asthma-symptom free days of each treatment period was calculated as the number of symptom-free days divided by the number of days on treatment multiplied by 100. A symptom-free day was defined as a day in which no asthma symptoms were recorded, no rescue medication was recorded, activities during the day were not at all limited due to asthma, no shortness of breath during the day was recorded, no wheezing or coughing during the day and no night-time awakenings due to asthma were recorded. Assessed by patients at home using the AM3 device.	0-3 weeks	No
Secondary	Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)	Assessed by patients at home using the AM3 device during each period of randomised treatment.	0-3 weeks	No
Secondary	Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)	Assessed by patients at home using the AM3 device during each period of randomised treatment .	0-3 weeks	No
Secondary	Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)	Assessed by patients at home using the AM3 device during each period of randomised treatment.	0-3 weeks	No
Secondary	Total Asthma Control Questionnaire (ACQ) Score	Control of asthma as assessed by the ACQ at the end of each 3-week treatment period.The ACQ contains 7 questions, each question has a 7 point scale from 0 (no symptoms) till 6 (highest intensity). Total score was defined as the sum of all items divided by the number of items.	3 weeks	No
Secondary	Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG	Clinical relevant abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	3 weeks + 12 days	No