Clinical trial NCT02085161: To Evaluate the Effect of Inhaled Medication Together With Exercise and Activity Training on Exercise Capacity and Daily Activities in Patients With Chronic Lung Disease With Obstruction of Airways
Official title: An Exploratory, 12 Week, Randomised, Partially Double-blinded, Placebo-controlled Parallel Group Trial to Explore the Effects of Once Daily Treatments of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination or Tiotropium (Both Delivered by Respimat® Inhaler), Supervised Exercise Training and Behavior Modification on Exercise Capacity and Physical Activity in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-03-12
Enrollment: 304
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of the study are to explore the effect of treatment with orally inhaled tiotropium + olodaterol fixed dose combination with and without exercise training, and tiotropium comparing to placebo, on top of behavioural modification in improving exercise capacity in patients with COPD


Eligibility criteria: Inclusion criteria:

* All patients must sign an informed consent consistent with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (GCP) guidelines prior to participation in the trial, which includes medication washout and restrictions.
* All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: Patients must have relatively stable airway obstruction with a post-bronchodilator forced expiratory volume in one second \>=30% and \<80% of predicted normal; Global Initiative for Chronic Obstructive Lung Disease grade II - III, and a post-bronchodilator Tiffeneau index \<70% at Visit 1.
* Male or female patients, aged \>=40 years and \<=75 years.
* Patients must be current or ex-smokers with a smoking history of more than 10 pack years. Patients who have never smoked cigarettes must be excluded.

Exclusion criteria:

* Patients with a significant disease other than chronic obstructive pulmonary disease.
* Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis.
* Patients with a history of asthma.
* A diagnosis of thyrotoxicosis.
* A diagnosis of paroxysmal tachycardia (\>100 beats per minute).
* A history of myocardial infarction within 1 year of screening visit.
* Unstable or life-threatening cardiac arrhythmia.
* Hospitalized for heart failure within the past year.
* Known active tuberculosis.
* A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years.
* A history of life-threatening pulmonary obstruction and patients with chronic respiratory failure.
* A history of cystic fibrosis.
* Clinically evident bronchiectasis.
* A history of significant alcohol or drug abuse.
* Any contraindications for exercise testing.
* Patients who have undergone thoracotomy with pulmonary resection.
* Patients being treated with any oral ß-adrenergics.
* Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.
* Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigators opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
* Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program.
* Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity.
* Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit.
* Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs, benzalkonium chloride, disodium edentat, or any other component of the Respimat® inhalation solution delivery system.
* Pregnant or nursing women.
* Women of childbearing potential not using highly effective methods of birth control.
* Patients who have previously been randomized in this study or are currently participating in another study.

Primary outcomes:
measure: Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 8 Weeks
timeFrame: Week 8
Secondary outcomes:
measure: Average Daily Walking Time Measured by the Activity Monitor in the Week Prior to Week 12
timeFrame: Week 12
measure: Average Daily Walking Intensity Measured by the Activity Monitor in the Week Prior to 12 Weeks of Treatment
timeFrame: Week 12
measure: Perceived Difficulties as Evaluated With Functional Performance Inventory-Short Form (FPI-SF) Total Score at Week 12
timeFrame: Week 12
measure: Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 12 Weeks
timeFrame: Week 12
measure: One Hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 8 Weeks of Treatment
timeFrame: Week 8
measure: One Hour, Post-dose Forced Vital Capacity (FVC) After 8 Weeks of Treatment
timeFrame: Week 8
measure: Resting Inspiratory Capacity (IC) Measured at 1.5 Hours Post Dose After 8 Weeks of Treatment
timeFrame: Week 8
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Torrance
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Hartford
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Connecticut
city: Daw Park
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: South Australia
city: Glen Osmond
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: South Australia
city: Salzburg
country: Austria
facility: Boehringer Ingelheim Investigational Site
city: Genk
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Hasselt
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Montreal
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Ste-Foy
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Kolding
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: København NV
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Odense
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Heidelberg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Leverkusen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Solingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Teuchern
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Tübingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Greenlane East Auckland NZ
country: New Zealand
facility: Boehringer Ingelheim Investigational Site
city: Gdansk
country: Poland
facility: Boehringer Ingelheim Investigational Site
city: Lodz
country: Poland
facility: Boehringer Ingelheim Investigational Site
city: Starachowice
country: Poland
facility: Boehringer Ingelheim Investigational Site
city: Coimbra
country: Portugal
facility: Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: Boehringer Ingelheim Investigational Site
city: Leicester
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Norwich
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Sheffield
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Troosters T, Bourbeau J, Maltais F, Leidy N, Erzen D, De Sousa D, Korducki L, Hamilton A. Enhancing exercise tolerance and physical activity in COPD with combined pharmacological and non-pharmacological interventions: PHYSACTO randomised, placebo-controlled study design. BMJ Open. 2016 Apr 13;6(4):e010106. doi: 10.1136/bmjopen-2015-010106.
citation: Bourbeau J, Lavoie KL, Sedeno M, De Sousa D, Erzen D, Hamilton A, Maltais F, Troosters T, Leidy N. Behaviour-change intervention in a multicentre, randomised, placebo-controlled COPD study: methodological considerations and implementation. BMJ Open. 2016 Apr 4;6(4):e010109. doi: 10.1136/bmjopen-2015-010109.