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CompletedNCT02085161Updated Jan 6, 2017Results posted

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

A Phase 3 interventional study of placebo to tiotropium + olodaterol and tiotropium+olodaterol in Pulmonary Disease, Chronic Obstructive, sponsored by Boehringer Ingelheim. Completed at 34 sites in 11 countries. Open to participants aged 40 Years to 75 Years. Per ClinicalTrials.gov, last updated 2017-01-06.

Sponsored by Boehringer Ingelheim · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
304
Allocation
Randomized
Ages
40 Years to 75 Years
Sex
All
01

Study 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

02

Conditions studied

  • Pulmonary Disease, Chronic Obstructive
03

In context

Lung Diseases

3,303 studies on the registry are indexed under Lung Diseases; 355 are open to participants now.

This study's enrollment of 304 is above the median of 72 across 2,118 interventional studies indexed under Lung Diseases.

Browse Lung Diseases studies →

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single
Enrollment
304 participants (actual)

Study arms

  • Placebo comparator
    placebo

    patient will receive placebo once daily, 2 puffs in the morning

    Drug: placebo to tiotropium + olodaterol

  • 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

    Drug: tiotropium +olodaterol

  • Active comparator
    tiotropium

    patient will receive tiotropium 5 mcg once daily, 2 puffs in the morning

    Drug: tiotropium

  • 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

    Drug: tiotropium+olodaterol

Interventions

  • Drugplacebo to tiotropium + olodaterol

    comparator

  • Drugtiotropium+olodaterol

    tiotropium 5 mcg once daily

  • Drugtiotropium +olodaterol

    olodaterol 5 mcg once daily fixed dose combination

  • Drugtiotropium

    tiotropium 5 mcg once daily fixed dose combination

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Week 8

Secondary outcomes

  1. 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.

    Time frame: Week 12

  2. 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.

    Time frame: Week 12

  3. 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.

    Time frame: Week 12

  4. 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.

    Time frame: Week 12

  5. 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.

    Time frame: Week 8

  6. 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.

    Time frame: Week 8

  7. 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.

    Time frame: Week 8

07

Results

Posted Jan 6, 2017

Participant flow

Participant flow — Overall Study
MilestonePlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM
Started76767676
Completed64667166
Not completed1210510
Withdrew: Not treated1000
Withdrew: Adverse event8545
Withdrew: Protocol violation0101
Withdrew: Withdrawal by subject2403
Withdrew: Other reason1011

Outcome measures

PrimaryEndurance 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.

Time frame:
Week 8
Reported as:
Geometric mean · Second
Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 8 Weeks
SecondPlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM
Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 8 Weeks244.07 ± 17.666254.18 ± 18.099315.32 ± 21.671355.73 ± 24.787
Statistical analysis
  • Placebo With Behavioural Modification (BM) vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.0002 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.458 · 95% CI 1.196 to 1.777Ratio of means calculated as back transformation of difference on log 10 scale between Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Placebo with behavioural modification (BM).
  • Placebo With Behavioural Modification (BM) vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.0109 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.292 · 95% CI 1.061 to 1.573Ratio of means calculated as back transformation of difference on log 10 scale between Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Placebo with behavioural modification (BM).
  • Placebo With Behavioural Modification (BM) vs Tiotropium (Tio) 5 Micro-grams (μg) With BM · ANCOVA · p = 0.6895 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.041 · 95% CI 0.853 to 1.272Ratio of means calculated as back transformation of difference on log 10 scale between Tiotropium (Tio) 5 micro-grams (μg) with BM minus Placebo with behavioural modification (BM).
  • Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.2188 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.128 · 95% CI 0.931 to 1.368Ratio of means calculated as back transformation of difference on log 10 scale between Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM.
  • Tiotropium (Tio) 5 Micro-grams (μg) With BM vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.0303 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.241 · 95% CI 1.021 to 1.507Ratio of means calculated as back transformation of difference on log 10 scale between Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Tiotropium (Tio) 5 micro-grams (μg) with BM.
SecondaryAverage 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.

Time frame:
Week 12
Reported as:
Least squares mean · Second
Average Daily Walking Time Measured by the Activity Monitor in the Week Prior to Week 12
SecondPlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM
Average Daily Walking Time Measured by the Activity Monitor in the Week Prior to Week 124670.78 ± 211.7984145.85 ± 207.3514831.85 ± 202.2614338.80 ± 207.252
Statistical analysis
  • Placebo With Behavioural Modification (BM) vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.2639 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: -331.975 · 95% CI -916.015 to 252.064The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.5837 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: 161.072 · 95% CI -417.314 to 739.459The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium (Tio) 5 Micro-grams (μg) With BM · ANCOVA · p = 0.0783 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: -524.926 · 95% CI -1109.806 to 59.954The LSMean Difference is calculated as Tiotropium (Tio) 5 micro-grams (μg) with BM minus Placebo with behavioural modification (BM)
  • Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.0900 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: -493.048 · 95% CI -1063.670 to 77.575The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM
  • Tiotropium (Tio) 5 Micro-grams (μg) With BM vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.0186 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: 685.998 · 95% CI 115.635 to 1256.362The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Tiotropium (Tio) 5 micro-grams (μg) with BM
SecondaryAverage 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.

Time frame:
Week 12
Reported as:
Least squares mean · Multiple of 9.8*(meters / (second^2))
Average Daily Walking Intensity Measured by the Activity Monitor in the Week Prior to 12 Weeks of Treatment
Multiple of 9.8*(meters / (second^2))Placebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM
Average Daily Walking Intensity Measured by the Activity Monitor in the Week Prior to 12 Weeks of Treatment0.20 ± 0.0030.20 ± 0.0030.20 ± 0.0030.20 ± 0.003
Statistical analysis
  • Placebo With Behavioural Modification (BM) vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.5186 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: -0.002 · 95% CI -0.010 to 0.005The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.6436 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: 0.002 · 95% CI -0.006 to 0.009The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium (Tio) 5 Micro-grams (μg) With BM · ANCOVA · p = 0.1081 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: -0.006 · 95% CI -0.014 to 0.001The LSMean Difference is calculated as Tiotropium (Tio) 5 micro-grams (μg) with BM minus Placebo with behavioural modification (BM)
  • Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.2612 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: -0.004 · 95% CI -0.011 to 0.003The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM
  • Tiotropium (Tio) 5 Micro-grams (μg) With BM vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.0361 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: 0.008 · 95% CI 0.001 to 0.015The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Tiotropium (Tio) 5 micro-grams (μg) with BM
SecondaryPerceived 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.

Time frame:
Week 12
Reported as:
Least squares mean · Units on a scale
Perceived Difficulties as Evaluated With Functional Performance Inventory-Short Form (FPI-SF) Total Score at Week 12
Units on a scalePlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM
Perceived Difficulties as Evaluated With Functional Performance Inventory-Short Form (FPI-SF) Total Score at Week 122.191 ± 0.0402.207 ± 0.0402.335 ± 0.0382.268 ± 0.039
Statistical analysis
  • Placebo With Behavioural Modification (BM) vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.1727 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: 0.076 · 95% CI -0.034 to 0.187The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.0097 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: 0.143 · 95% CI 0.035 to 0.252The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium (Tio) 5 Micro-grams (μg) With BM · ANCOVA · p = 0.7815 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: 0.016 · 95% CI -0.095 to 0.126The LSMean Difference is calculated as Tiotropium (Tio) 5 micro-grams (μg) with BM minus Placebo with behavioural modification (BM)
  • Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.2183 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: -0.067 · 95% CI -0.174 to 0.040The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM
  • Tiotropium (Tio) 5 Micro-grams (μg) With BM vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.0203 (An ANCOVA model with categorical effects of treatment and baseline as covariate.) · Lsmean difference: 0.128 · 95% CI 0.020 to 0.236The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Tiotropium (Tio) 5 micro-grams (μg) with BM
SecondaryEndurance 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.

Time frame:
Week 12
Reported as:
Geometric mean · Second
Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 12 Weeks
SecondPlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM
Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 12 Weeks243.30 ± 18.680255.67 ± 19.292302.61 ± 21.691324.21 ± 24.095
Statistical analysis
  • Placebo With Behavioural Modification (BM) vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.0077 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.333 · 95% CI 1.080 to 1.645Ratio of means calculated as back transformation of difference on log 10 scale between Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Placebo with behavioural modification (BM).
  • Placebo With Behavioural Modification (BM) vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.0390 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.244 · 95% CI 1.011 to 1.530Ratio of means calculated as back transformation of difference on log 10 scale between Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Placebo with behavioural modification (BM).
  • Placebo With Behavioural Modification (BM) vs Tiotropium (Tio) 5 Micro-grams (μg) With BM · ANCOVA · p = 0.6452 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.051 · 95% CI 0.850 to 1.299Ratio of means calculated as back transformation of difference on log 10 scale between Tiotropium (Tio) 5 micro-grams (μg) with BM minus Placebo with behavioural modification (BM).
  • Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · ANCOVA · p = 0.5048 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.071 · 95% CI 0.874 to 1.313Ratio of means calculated as back transformation of difference on log 10 scale between Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM.
  • Tiotropium (Tio) 5 Micro-grams (μg) With BM vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · ANCOVA · p = 0.1066 (ANCOVA model with categorical effect of treatment and baseline as covariate.) · Treatment ratio: 1.184 · 95% CI 0.964 to 1.453Ratio of means calculated as back transformation of difference on log 10 scale between Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Tiotropium (Tio) 5 micro-grams (μg) with BM.
SecondaryOne 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.

Time frame:
Week 8
Reported as:
Least squares mean · Liter
One Hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 8 Weeks of Treatment
LiterPlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM
One Hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 8 Weeks of Treatment1.375 ± 0.0271.550 ± 0.0271.731 ± 0.0261.705 ± 0.026
Statistical analysis
  • Placebo With Behavioural Modification (BM) vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · Mixed Models Analysis · p = <0.0001 (Mixed effect Model Repeat Measurement (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.329 · 95% CI 0.255 to 0.403The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · Mixed Models Analysis · p = <0.0001 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.356 · 95% CI 0.282 to 0.429The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium (Tio) 5 Micro-grams (μg) With BM · Mixed Models Analysis · p = <0.0001 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.174 · 95% CI 0.099 to 0.249The LSMean Difference is calculated as Tiotropium (Tio) 5 micro-grams (μg) with BM minus Placebo with behavioural modification (BM)
  • Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · Mixed Models Analysis · p = 0.4677 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: -0.027 · 95% CI -0.099 to 0.045The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM
  • Tiotropium (Tio) 5 Micro-grams (μg) With BM vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · Mixed Models Analysis · p = <0.0001 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.182 · 95% CI 0.109 to 0.255The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Tiotropium (Tio) 5 micro-grams (μg) with BM
SecondaryOne 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.

Time frame:
Week 8
Reported as:
Least squares mean · Liter
One Hour, Post-dose Forced Vital Capacity (FVC) After 8 Weeks of Treatment
LiterPlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM
One Hour, Post-dose Forced Vital Capacity (FVC) After 8 Weeks of Treatment2.974 ± 0.0473.259 ± 0.0463.504 ± 0.0443.452 ± 0.045
Statistical analysis
  • Placebo With Behavioural Modification (BM) vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · Mixed Models Analysis · p = <0.0001 (Mixed effect Model Repeat Measurement (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.478 · 95% CI 0.350 to 0.606The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · Mixed Models Analysis · p = <0.0001 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.530 · 95% CI 0.403 to 0.657The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium (Tio) 5 Micro-grams (μg) With BM · Mixed Models Analysis · p = <0.0001 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.286 · 95% CI 0.157 to 0.415The LSMean Difference is calculated as Tiotropium (Tio) 5 micro-grams (μg) with BM minus Placebo with behavioural modification (BM)
  • Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · Mixed Models Analysis · p = 0.4107 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: -0.052 · 95% CI -0.176 to 0.072The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM
  • Tiotropium (Tio) 5 Micro-grams (μg) With BM vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · Mixed Models Analysis · p = 0.0002 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.244 · 95% CI 0.119 to 0.370The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Tiotropium (Tio) 5 micro-grams (μg) with BM
SecondaryResting 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.

Time frame:
Week 8
Reported as:
Least squares mean · Liter
Resting Inspiratory Capacity (IC) Measured at 1.5 Hours Post Dose After 8 Weeks of Treatment
LiterPlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM
Resting Inspiratory Capacity (IC) Measured at 1.5 Hours Post Dose After 8 Weeks of Treatment2.452 ± 0.0512.627 ± 0.0502.755 ± 0.0482.771 ± 0.049
Statistical analysis
  • Placebo With Behavioural Modification (BM) vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · Mixed Models Analysis · p = <0.0001 (Mixed effect Model Repeat Measurement (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.318 · 95% CI 0.179 to 0.457The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · Mixed Models Analysis · p = <0.0001 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.302 · 95% CI 0.165 to 0.439The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Placebo with behavioural modification (BM)
  • Placebo With Behavioural Modification (BM) vs Tiotropium (Tio) 5 Micro-grams (μg) With BM · Mixed Models Analysis · p = 0.0145 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.174 · 95% CI 0.035 to 0.314The LSMean Difference is calculated as Tiotropium (Tio) 5 micro-grams (μg) with BM minus Placebo with behavioural modification (BM)
  • Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM vs Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM · Mixed Models Analysis · p = 0.8150 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.016 · 95% CI -0.118 to 0.151The LSMean Difference is calculated as Tio+Olo (5/5 μg) FDC with exercise training (ET) and BM minus Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM
  • Tiotropium (Tio) 5 Micro-grams (μg) With BM vs Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM · Mixed Models Analysis · p = 0.0642 (MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect) · Lsmean difference: 0.128 · 95% CI -0.008 to 0.263The LSMean Difference is calculated as Tiotropium + olodaterol (Olo) (5/5 μg) FDC with BM minus Tiotropium (Tio) 5 micro-grams (μg) with BM

Adverse events

Collected over From first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period, up to 134 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo With Behavioural Modification (BM)—4/75 (5.3%)22/75 (29.3%)
Tiotropium (Tio) 5 Micro-grams (μg) With BM—11/76 (14.5%)19/76 (25%)
Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM—3/76 (3.9%)16/76 (21.1%)
Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM—8/76 (10.5%)19/76 (25%)
Total—26/303 (8.6%)76/303 (25.1%)
Most frequent serious events
Showing 10 of 34
Most frequent serious events
EventPlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BMTotal
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders1/752/761/761/765/303
Coronary artery diseaseCardiac disorders1/750/760/760/761/303
HepatotoxicityHepatobiliary disorders1/750/760/760/761/303
Alcohol poisoningInjury, poisoning and procedural complications1/750/760/760/761/303
Non-Hodgkin's lymphoma unspecified histology indolent stage IVNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/750/760/760/761/303
Pulmonary hilum massRespiratory, thoracic and mediastinal disorders1/750/760/760/761/303
Acute myocardial infarctionCardiac disorders0/750/760/761/761/303
Angina pectorisCardiac disorders0/750/760/761/761/303
Atrial fibrillationCardiac disorders0/750/761/760/761/303
CholelithiasisHepatobiliary disorders0/751/760/760/761/303
Most frequent other events
Most frequent other events
EventPlacebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BMTotal
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders16/7510/7612/7613/7651/303
NasopharyngitisInfections and infestations8/759/764/7610/7631/303
DyspnoeaRespiratory, thoracic and mediastinal disorders2/756/762/762/7612/303
Back painMusculoskeletal and connective tissue disorders4/751/762/761/768/303

Baseline characteristics

Treated set (TS): This patient set included all patients of the Randomised set (All patients who signed informed consent form and were also randomised, regardless whether the patient was treated with study medication or not.) who were dispensed study medication and were documented to have taken any dose of study medication.

Age, Continuous
Age, Continuous(Years)Placebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BMTotal
Mean64.4 ± 6.665.1 ± 6.465.0 ± 6.964.7 ± 6.564.8 ± 6.6
Gender
Gender(Participants)Placebo With Behavioural Modification (BM)Tiotropium (Tio) 5 Micro-grams (μg) With BMTiotropium + Olodaterol (Olo) (5/5 μg) FDC With BMTio+Olo (5/5 μg) FDC With Exercise Training (ET) and BMTotal
Female23212831103
Male52554845200
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Study locations

34 sites
  • Boehringer Ingelheim Investigational Site
    San Diego, California, United States
  • Boehringer Ingelheim Investigational Site
    Torrance, California, United States
  • Boehringer Ingelheim Investigational Site
    Hartford, Connecticut, United States
  • Boehringer Ingelheim Investigational Site
    Daw Park, South Australia, Australia
  • Boehringer Ingelheim Investigational Site
    Glen Osmond, South Australia, Australia
  • Boehringer Ingelheim Investigational Site
    Salzburg, Austria
  • Boehringer Ingelheim Investigational Site
    Genk, Belgium
  • Boehringer Ingelheim Investigational Site
    Hasselt, Belgium
  • Boehringer Ingelheim Investigational Site
    Leuven, Belgium
  • Boehringer Ingelheim Investigational Site
    Montreal, Quebec, Canada
  • Boehringer Ingelheim Investigational Site
    Ste-Foy, Quebec, Canada
  • Boehringer Ingelheim Investigational Site
    Saskatoon, Saskatchewan, Canada
  • Boehringer Ingelheim Investigational Site
    Kolding, Denmark
  • Boehringer Ingelheim Investigational Site
    København NV, Denmark
  • Boehringer Ingelheim Investigational Site
    Odense, Denmark
  • Boehringer Ingelheim Investigational Site
    Berlin, Germany
  • Boehringer Ingelheim Investigational Site
    Bochum, Germany
  • Boehringer Ingelheim Investigational Site
    Frankfurt, Germany
  • Boehringer Ingelheim Investigational Site
    Großhansdorf, Germany
  • Boehringer Ingelheim Investigational Site
    Heidelberg, Germany
  • Boehringer Ingelheim Investigational Site
    Leverkusen, Germany
  • Boehringer Ingelheim Investigational Site
    Solingen, Germany
  • Boehringer Ingelheim Investigational Site
    Teuchern, Germany
  • Boehringer Ingelheim Investigational Site
    Tübingen, Germany
  • Boehringer Ingelheim Investigational Site
    Greenlane East Auckland NZ, New Zealand
  • Boehringer Ingelheim Investigational Site
    Gdansk, Poland
  • Boehringer Ingelheim Investigational Site
    Lodz, Poland
  • Boehringer Ingelheim Investigational Site
    Starachowice, Poland
  • Boehringer Ingelheim Investigational Site
    Coimbra, Portugal
  • Boehringer Ingelheim Investigational Site
    Lisboa, Portugal
  • Boehringer Ingelheim Investigational Site
    Porto, Portugal
  • Boehringer Ingelheim Investigational Site
    Leicester, United Kingdom
  • Boehringer Ingelheim Investigational Site
    Norwich, United Kingdom
  • Boehringer Ingelheim Investigational Site
    Sheffield, United Kingdom
09

References and documents

Publications

  • 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. PubMed 27075841 ↗
  • 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. PubMed 27044576 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 6, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02085161
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Mar 12, 2014
Start date
Mar 2014
Primary completion
Aug 2015
Completion
Oct 2015
Results posted
Jan 6, 2017
Last update
Jan 6, 2017

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

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