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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02085161




Registration number
NCT02085161
Ethics application status
Date submitted
7/03/2014
Date registered
12/03/2014
Date last updated
6/01/2017

Titles & IDs
Public title
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
Scientific 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)
Secondary ID [1] 0 0
2013-002671-18
Secondary ID [2] 0 0
1237.16
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - placebo to tiotropium + olodaterol
Treatment: Drugs - tiotropium+olodaterol
Treatment: Drugs - tiotropium +olodaterol
Treatment: Drugs - tiotropium

Placebo Comparator: placebo - patient will receive placebo once daily, 2 puffs in the morning

Experimental: tiotropium + olodaterol high dose with BM - patient will receive tiotropium 5 mcg + olodaterol 5 mcg in fixed dose combination once daily, 2 puffs in the morning

Active Comparator: tiotropium - patient will receive tiotropium 5 mcg once daily, 2 puffs in the morning

Experimental: tiotropium + olodaterol with exercise training and BM - patient will receive tiotropium 5 mcg + olodaterol 5 mcg in fixed dose combination once daily, 2 puffs in the morning


Treatment: Drugs: placebo to tiotropium + olodaterol
comparator

Treatment: Drugs: tiotropium+olodaterol
tiotropium 5 mcg once daily

Treatment: Drugs: tiotropium +olodaterol
olodaterol 5 mcg once daily fixed dose combination

Treatment: Drugs: tiotropium
tiotropium 5 mcg once daily fixed dose combination

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 8 Weeks - Endurance time during ESWT to symptom limitation at walking speed corresponding to 85% of predicted maximum oxygen consumption (VO2 peak) after 8 weeks of pharmacological treatment and non-pharmacological intervention. The numerical value of endurance time in seconds was transformed in log10 scale to correct for skewness and then an analysis of covariance (ANCOVA) was fitted to the log10-transformed data and the least square means (LSMean) and standard error (SE) were obtained. To present the results in a way easier for interpretation, the least square mean from the ANCOVA fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate to obtain the geometric mean and the corresponding SE was transformed using delta method to get the corresponding SE of the geometric mean.
Timepoint [1] 0 0
Week 8
Secondary outcome [1] 0 0
Average Daily Walking Time Measured by the Activity Monitor in the Week Prior to Week 12 - Average daily walking time measured by the activity monitor in the week prior to Week 12.
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Average Daily Walking Intensity Measured by the Activity Monitor in the Week Prior to 12 Weeks of Treatment - Average daily walking intensity measured by the activity monitor in the week prior to 12 weeks of treatment. The Movement Intensity (MI) is derived from the acceleration signals. Since seismic sensors measure gravitational acceleration (g) in static situations, the acceleration signal is expressed relative to g (1g = 9.81m/s2). To calculate movement intensity (MI) the gravitational acceleration in static situations was removed and the rotation vector of the three accelerometer signals was calculated. The MI gives an indication of the power of movements.
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Perceived Difficulties as Evaluated With Functional Performance Inventory-Short Form (FPI-SF) Total Score at Week 12 - Perceived difficulties as evaluated with FPI-SF. FPI-SF self-report questionnaire has 6 domains: Body care(5 items), Household maintenance(8 items), Physical exercise(5 items), Recreation(5 items), Spiritual activities(4 items) and Social interaction(5 items) with five possible answers on each item: Do with no difficulty - 3, Do with some difficulty - 2, Do with great difficulty - 1, don't do because of health reasons - 0, and don't do because choose not to - 0. Domain scores are expressed as mean values, with at least 6 non-missing items required for the household maintenance domain and at least 3 non-missing items for the other domains. Total score is the mean across the six domains. So total and domain scores range from 0 to 3, with higher scores indicating higher levels of functional activity within and across domains. Respondents engaged in many activities with no difficulty will score high on the FPI, while those who perform few activities with much difficulty will score low.
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 12 Weeks - Endurance time during ESWT to symptom limitation at walking speed corresponding to 85% of maximum oxygen consumption (VO2 peak) after 12 weeks of pharmacological treatment and non-pharmacological intervention. The numerical value of endurance time in seconds was transformed in log10 scale to correct for skewness and then the ANCOVA was fitted to the log10-transformed data and the least square means and SE were obtained. To present the results in a way easier for interpretation, the least square mean from the ANCOVA fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate to obtain the geometric mean and the corresponding SE was transformed using delta method to get the corresponding SE of the geometric mean.
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
One Hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 8 Weeks of Treatment - One hour, Post-dose Forced Expiratory Volume in One Second (FEV1) after 8 weeks of treatment.
Timepoint [5] 0 0
Week 8
Secondary outcome [6] 0 0
One Hour, Post-dose Forced Vital Capacity (FVC) After 8 Weeks of Treatment - One hour, Post-dose Forced Vital Capacity (FVC) after 8 weeks of treatment.
Timepoint [6] 0 0
Week 8
Secondary outcome [7] 0 0
Resting Inspiratory Capacity (IC) Measured at 1.5 Hours Post Dose After 8 Weeks of Treatment - Resting inspiratory capacity (IC) measured at 1.5 hours post dose after 8 weeks of treatment.
Timepoint [7] 0 0
Week 8

Eligibility
Key inclusion 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.
Minimum age
40 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Boehringer Ingelheim Investigational Site - Daw Park
Recruitment hospital [2] 0 0
Boehringer Ingelheim Investigational Site - Glen Osmond
Recruitment postcode(s) [1] 0 0
- Daw Park
Recruitment postcode(s) [2] 0 0
- Glen Osmond
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
Austria
State/province [3] 0 0
Salzburg
Country [4] 0 0
Belgium
State/province [4] 0 0
Genk
Country [5] 0 0
Belgium
State/province [5] 0 0
Hasselt
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Canada
State/province [8] 0 0
Saskatchewan
Country [9] 0 0
Denmark
State/province [9] 0 0
Kolding
Country [10] 0 0
Denmark
State/province [10] 0 0
København NV
Country [11] 0 0
Denmark
State/province [11] 0 0
Odense
Country [12] 0 0
Germany
State/province [12] 0 0
Berlin
Country [13] 0 0
Germany
State/province [13] 0 0
Bochum
Country [14] 0 0
Germany
State/province [14] 0 0
Frankfurt
Country [15] 0 0
Germany
State/province [15] 0 0
Großhansdorf
Country [16] 0 0
Germany
State/province [16] 0 0
Heidelberg
Country [17] 0 0
Germany
State/province [17] 0 0
Leverkusen
Country [18] 0 0
Germany
State/province [18] 0 0
Solingen
Country [19] 0 0
Germany
State/province [19] 0 0
Teuchern
Country [20] 0 0
Germany
State/province [20] 0 0
Tübingen
Country [21] 0 0
New Zealand
State/province [21] 0 0
Greenlane East Auckland NZ
Country [22] 0 0
Poland
State/province [22] 0 0
Gdansk
Country [23] 0 0
Poland
State/province [23] 0 0
Lodz
Country [24] 0 0
Poland
State/province [24] 0 0
Starachowice
Country [25] 0 0
Portugal
State/province [25] 0 0
Coimbra
Country [26] 0 0
Portugal
State/province [26] 0 0
Lisboa
Country [27] 0 0
Portugal
State/province [27] 0 0
Porto
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Leicester
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Norwich
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT02085161
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications