Clinical trial NCT01311661: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-03-09
Enrollment: 206
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: 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).


Eligibility criteria: 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.

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, 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
Secondary outcomes:
measure: FEV1 Area Under Curve 0-12 Hours (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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks
measure: FEV1 Area Under Curve 12-24 Hours (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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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, 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
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 morning dose after 3 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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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 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
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, 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
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 morning dose after 3 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, 6 h, 8h, 10 h, 11 h 50 min related to morning dose after 3 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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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 -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
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, 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
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 morning dose after 3 weeks
measure: Mean Pre-dose Morning PEF (PEF a.m.)
timeFrame: 0-3 weeks
measure: Mean Pre-dose Evening PEF (PEF p.m.)
timeFrame: 0-3 weeks
measure: PEF Daily Variability
timeFrame: 0-3 weeks
measure: Mean Pre-dose Morning FEV1 (FEV1 a.m.)
timeFrame: 0-3 weeks
measure: Mean Pre-dose Evening FEV1 (FEV1 p.m.)
timeFrame: 0-3 weeks
measure: Mean Number of Puffs of Rescue Medication During the Whole Day
timeFrame: 0-3 weeks
measure: Percentage of Asthma Symptom Free Days
timeFrame: 0-3 weeks
measure: Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
timeFrame: 0-3 weeks
measure: Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
timeFrame: 0-3 weeks
measure: Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
timeFrame: 0-3 weeks
measure: Total Asthma Control Questionnaire (ACQ) Score
timeFrame: 3 weeks
measure: Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
timeFrame: 3 weeks + 12 days
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: 1222.29.11006 Boehringer Ingelheim Investigational Site
state: California
city: Centennial
country: United States
facility: 1222.29.11001 Boehringer Ingelheim Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: 1222.29.11012 Boehringer Ingelheim Investigational Site
state: Colorado
city: Overland Park
country: United States
facility: 1222.29.11002 Boehringer Ingelheim Investigational Site
state: Kansas
city: North Dartmouth
country: United States
facility: 1222.29.11004 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: St. Louis
country: United States
facility: 1222.29.11011 Boehringer Ingelheim Investigational Site
state: Missouri
city: Skillman
country: United States
facility: 1222.29.11009 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Raleigh
country: United States
facility: 1222.29.11003 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Canton
country: United States
facility: 1222.29.11008 Boehringer Ingelheim Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: 1222.29.11007 Boehringer Ingelheim Investigational Site
state: Ohio
city: Spartanburg
country: United States
facility: 1222.29.11005 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Richmond
country: United States
facility: 1222.29.11010 Boehringer Ingelheim Investigational Site
state: Virginia
city: Linz
country: Austria
facility: 1222.29.43003 Boehringer Ingelheim Investigational Site
city: Schlüsslberg
country: Austria
facility: 1222.29.43002 Boehringer Ingelheim Investigational Site
city: Thalheim bei Wels
country: Austria
facility: 1222.29.43001 Boehringer Ingelheim Investigational Site
city: Wels
country: Austria
facility: 1222.29.43004 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.29.49004 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.29.49006 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.29.49007 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1222.29.49008 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1222.29.49002 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 1222.29.49010 Boehringer Ingelheim Investigational Site
city: Lübeck
country: Germany
facility: 1222.29.49003 Boehringer Ingelheim Investigational Site
city: Rüdersdorf
country: Germany
facility: 1222.29.49005 Boehringer Ingelheim Investigational Site
city: Wiesbaden
country: Germany
facility: 1222.29.49001 Boehringer Ingelheim Investigational Site
city: Wiesloch
country: Germany
facility: 1222.29.49009 Boehringer Ingelheim Investigational Site
city: Mosonmagyarovar
country: Hungary
facility: 1222.29.36002 Boehringer Ingelheim Investigational Site
city: Nyiregyhaza
country: Hungary
facility: 1222.29.36003 Boehringer Ingelheim Investigational Site
city: Sopron
country: Hungary
facility: 1222.29.36001 Boehringer Ingelheim Investigational Site
city: Zalaegerszeg
country: Hungary
facility: 1222.29.36004 Boehringer Ingelheim Investigational Site
city: Bardejov
country: Slovakia
facility: 1222.29.42001 Boehringer Ingelheim Investigational Site
city: Martin
country: Slovakia
facility: 1222.29.42002 Boehringer Ingelheim Investigational Site
city: Nitra
country: Slovakia
facility: 1222.29.42004 Boehringer Ingelheim Investigational Site
city: Spisska Nova Ves
country: Slovakia
facility: 1222.29.42003 Boehringer Ingelheim Investigational Site
city: Golnik
country: Slovenia
facility: 1222.29.38003 Boehringer Ingelheim Investigational Site
city: Kamnik
country: Slovenia
facility: 1222.29.38002 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Beeh KM, LaForce C, Gahlemann M, Wenz A, Toorawa R, Flezar M. Randomised, double-blind, placebo-controlled crossover study to investigate different dosing regimens of olodaterol delivered via Respimat(R) in patients with moderate to severe persistent asthma. Respir Res. 2015 Jul 16;16(1):87. doi: 10.1186/s12931-015-0243-1.