ClinicalTrials.gg
Sign In
CompletedNCT01525615Updated Aug 29, 2016Results posted

A Study to Determine the Effect of Tiotropium + Olodaterol Fixed Dose Combination on Exercise Endurance Time During Constant Work Rate Cycle Ergometry Test in COPD

A Phase 3 interventional study of Respimat inhaler and tiotropium+olodaterol (low dose) in Pulmonary Disease, Chronic Obstructive, sponsored by Boehringer Ingelheim. Completed at 60 sites in 10 countries. Open to participants aged 40 Years to 75 Years. Per ClinicalTrials.gov, last updated 2016-08-29.

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

Phase
Phase 3
Study type
Interventional
Enrollment
404
Allocation
Randomized
Ages
40 Years to 75 Years
Sex
All
01

Study summary

The primary objective of this study is to compare the effects of orally inhaled tiotropium + olodaterol fixed dose combination (2.5/5 µg; 5/5 µg) with placebo on exercise tolerance after 12 weeks of treatment in patients with COPD.

02

Conditions studied

  • Pulmonary Disease, Chronic Obstructive
03

In context

Pulmonary Disease, Chronic Obstructive

4,252 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 707 are open to participants now.

This study's enrollment of 404 is above the median of 70 across 3,008 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.

Browse Pulmonary Disease, Chronic Obstructive studies →

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,297 studies on the registry; 56 are open to participants now.

Of its 166 completed or terminated interventional studies of FDA-regulated products, 121 (73%) have results posted.

Browse Boehringer Ingelheim studies →

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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.

  2. 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, at visit 1:

    a post-bronchodilator 30% \<= FEV1 \<80% of predicted normal (ECSC) and a post-bronchodilator FEV1/FVC \<70% at Visit 1

  3. Male or female patients, between 40 and 75 years (inclusive) of age on day of signing informed consent.
  4. 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.
  5. Patients must be able to perform technically acceptable pulmonary function tests (spirometry), must be able to complete multiple symptom-limited cycle ergometry tests (and for a subset also shuttle walk tests), as required in the protocol.
  6. Patients must be able to inhale medication in a competent manner from the RESPIMAT inhaler and from a metered dose inhaler (MDI).

Exclusion criteria

Exclusion criteria:

  1. Patients with a significant disease other than COPD
  2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT > x2 ULN, SGPT > x2 ULN, bilirubin > x2 ULN or creatinine > x2 ULN will be excluded regardless of clinical condition
  3. Patients with a history of asthma
  4. A diagnosis of thyrotoxicosis
  5. A diagnosis of paroxysmal tachycardia (>100 beats per minute)
  6. A history of myocardial infarction within 1 year of screening visit (Visit 1)
  7. Unstable or life-threatening cardiac arrhythmia
  8. Hospitalized for heart failure within the past year
  9. Known active tuberculosis
  10. A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
  11. A history of life-threatening pulmonary obstruction and patients with chronic respiratory failure
  12. A history of cystic fibrosis
  13. Clinically evident bronchiectasis
  14. A history of significant alcohol or drug abuse
  15. Any contraindications for exercise testing
  16. Patients who have undergone thoracotomy with pulmonary resection
  17. Patients being treated with any oral ß-adrenergics
  18. 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
  19. Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits
  20. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program
  21. Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea or morbid obesity
  22. Patients with an endurance time >=25 minutes during the training (Visit 2) or baseline (Visit 3) constant work rate cycle ergometry
  23. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit (Visit 1)
  24. Patients with known hypersensitivity to ß-adrenergic drugs, anticholinergic drugs, BAC, EDTA or any other component of the RESPIMAT inhalation solution delivery system
  25. Pregnant or nursing women

  26. Women of childbearing potential not using a highly effective method of birth control.

    Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years

  27. Patients who have previously been randomized in this study or are currently participating in another study

  28. Patients who are unable to comply with pulmonary medication restrictions prior to randomization

    At sites performing the shuttle walk tests, patients with the following criteria will be excluded from the shuttle walk tests:

  29. Patients who complete level 12 at the incremental shuttle walk test at visit 1a.
  30. Patients with an endurance time >=15 minutes during the training (Visit 2a) or baseline (visit 3a) endurance shuttle walk test.
05

Study design

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

Study arms

  • Experimental
    tiotropium+olodaterol low dose

    once daily 2 puffs, fixed dose combination (FDC) solution for inhalation Respimat

    Device: Respimat inhaler · Drug: tiotropium+olodaterol (low dose)

  • Experimental
    tiotropium+olodaterol high dose

    once daily 2 puffs, FDC solution for inhalation Respimat

    Drug: tiotropium + olodaterol (high dose) · Device: Respimat inhaler

  • Placebo comparator
    placebo

    once daily 2 puffs, solution for inhalation Respimat

    Device: Respimat inhaler · Drug: placebo to tiotropium+olodaterol

Interventions

  • DeviceRespimat inhaler

    Respimat inhaler

  • Drugtiotropium+olodaterol (low dose)

    Drug pages: Tiotropium · Olodaterol

    2.5 µg tiotropium + 5 µg olodaterol

  • Drugtiotropium + olodaterol (high dose)

    Drug pages: Tiotropium · Olodaterol

    5 µg tiotropium + 5 µg olodaterol

  • DeviceRespimat inhaler

    Respimat inhaler

  • DeviceRespimat inhaler

    Respimat inhaler

  • Drugplacebo to tiotropium+olodaterol

    comparator

06

What researchers measure

Primary outcomes

  1. Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 12 Weeks

    Primary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 12 weeks of treatment. The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.

    Time frame: 12 weeks

Secondary outcomes

  1. Adjusted Mean Endurance Time During Endurance Shuttle Walk Test (ESWT) After 12 Weeks

    Key secondary endpoint was endurance time during endurance shuttle walk test to symptom limitation at 85% of predicted maximum oxygen consumption (VO2) peak after 12 weeks of treatment. The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.

    Time frame: 12 weeks

  2. Adjusted Mean Inspiratory Capacity at Pre-exercise After 12 Weeks

    Secondary endpoint was pre-exercise inspiratory capacity (IC) before constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) after 12 weeks of treatment.

    Time frame: 12 weeks

  3. Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) on Day 1

    Secondary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity on Day 1. Analysis of covariance model on log10 transformation data. Adjusted means are back transformed to report in original units. Standard errors (SEs) are calculated using the delta method.

    Time frame: 1 day

  4. Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 6 Weeks Treatment

    Secondary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment.The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.

    Time frame: 6 weeks

  5. Adjusted Mean Inspiratory Capacity at Pre-exercise After 1 Day

    Secondary endpoint was pre-exercise inspiratory capacity (IC) during constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) on Day 1.

    Time frame: 1 day

  6. Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks

    Secondary endpoint was pre-exercise inspiratory capacity (IC) during constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) after 6 weeks of treatment.

    Time frame: 6 weeks

  7. Adjusted Mean Slope of the Intensity of Breathing Discomfort on Day 1

    Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 1 day of treatment. The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates slowing down in decline in breathing, i.e., favorable results.

    Time frame: 1 day

  8. Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 6

    Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment. The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates favorable results.

    Time frame: 6 weeks

  9. Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 12

    Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 12 weeks of treatment. The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates favorable results.

    Time frame: 12 weeks

  10. Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) on Day 1

    Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed on day 1

    Time frame: 1 day

  11. Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 6 Weeks

    Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 6 weeks of treatment

    Time frame: 6 weeks

  12. Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 12 Weeks

    Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 12 weeks of treatment

    Time frame: 12 weeks

07

Results

Posted Sep 15, 2015

Participant flow

Participant flow — Overall Study
MilestonePlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Started132133139
Completed118126133
Not completed1476
Withdrew: Adverse event1175
Withdrew: Lost to follow-up100
Withdrew: Withdrawal by subject100
Withdrew: Other reason not described above101

Outcome measures

PrimaryAdjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 12 Weeks

Primary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 12 weeks of treatment. The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.

Time frame:
12 weeks
Reported as:
Least squares mean · seconds
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 12 Weeks
secondsPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 12 Weeks463.63 ± 18.813503.64 ± 19.642527.51 ± 20.154
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.0209 (Mixed effects Model for Repeated Measures (MMRM) with fixed effects of treatment, test day, treatment by test day interaction, log10 (baseline endurance time), log10 (baseline endurance time) by test day interaction, and patient as a random effect.) · Treatment ratio: 1.138 · 95% CI 1.020 to 1.269Mean and 95% confidence limits were transformed from log10 back to the original scale. SE was calculated using the delta method.
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = 0.1419 (MMRM model for log10 (endurance time \[s\]) with fixed effects of treatment, test day, treatment by test day interaction, log10 (baseline endurance time \[s\]), log10 (baseline endurance time \[s\]) by test day interaction, patient as a random effect.) · Treatment ratio: 1.086 · 95% CI 0.973 to 1.213Mean and 95% confidence limits were transformed from log10 back to the original scale. SE was calculated using the delta method.
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.3970 (MMRM model for log10 (endurance time \[s\]) with fixed effects of treatment, test day, treatment by test day interaction, log10 (baseline endurance time \[s\]), log10 (baseline endurance time \[s\]) by test day interaction, patient as a random effect.) · Treatment ratio: 1.047 · 95% CI 0.941 to 1.166Mean and 95% confidence limits were transformed from log10 back to the original scale. SE was calculated using the delta method.
SecondaryAdjusted Mean Endurance Time During Endurance Shuttle Walk Test (ESWT) After 12 Weeks

Key secondary endpoint was endurance time during endurance shuttle walk test to symptom limitation at 85% of predicted maximum oxygen consumption (VO2) peak after 12 weeks of treatment. The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.

Time frame:
12 weeks
Reported as:
Least squares mean · seconds
Adjusted Mean Endurance Time During Endurance Shuttle Walk Test (ESWT) After 12 Weeks
secondsPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Endurance Time During Endurance Shuttle Walk Test (ESWT) After 12 Weeks311.41 ± 22.519377.20 ± 25.942376.39 ± 25.033
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.0552 (MMRM model for log10 (endurance time \[s\]) with fixed effects of treatment, test day, treatment by test day interaction, log10 (baseline endurance time \[s\]), log10 (baseline endurance time \[s\]) by test day interaction, patient as a random effect.) · Tretament ratio: 1.209 · 95% CI 0.996 to 1.467Mean and 95% confidence limits were transformed from log10 back to the original scale. SE was calculated using the delta method.
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = 0.0562 (MMRM model for log10 (endurance time \[s\]) with fixed effects of treatment, test day, treatment by test day interaction, log10 (baseline endurance time \[s\]), log10 (baseline endurance time \[s\]) by test day interaction, patient as a random effect.) · Treatment ratio: 1.211 · 95% CI 0.995 to 1.475Mean, 95% confidence limits transformed from log10 to original scale. SE was calculated using the delta method. This hypothesis test is descriptive.
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.9822 (MMRM model for log10 (endurance time \[s\]) with fixed effects of treatment, test day, treatment by test day interaction, log10 (baseline endurance time \[s\]), log10 (baseline endurance time \[s\]) by test day interaction, patient as a random effect.) · Treatment ratio: 0.998 · 95% CI 0.826 to 1.205Mean and 95% confidence limits were transformed from log10 back to the original scale. SE was calculated using the delta method.
SecondaryAdjusted Mean Inspiratory Capacity at Pre-exercise After 12 Weeks

Secondary endpoint was pre-exercise inspiratory capacity (IC) before constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) after 12 weeks of treatment.

Time frame:
12 weeks
Reported as:
Least squares mean · liters
Adjusted Mean Inspiratory Capacity at Pre-exercise After 12 Weeks
litersPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Inspiratory Capacity at Pre-exercise After 12 Weeks2.390 ± 0.0382.597 ± 0.0362.624 ± 0.035
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = <0.0001 (MMRM model for inspiratory capacity with fixed effects of treatment, test day, treatment by test day interaction, baseline inspiratory capacity, baseline inspiratory capacity by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.234 · 95% CI 0.133 to 0.336LSMean=Least square mean.
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = <0.0001 (MMRM model for inspiratory capacity with fixed effects of treatment, test day, treatment by test day interaction, baseline inspiratory capacity, baseline inspiratory capacity by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.207 · 95% CI 0.105 to 0.309This hypothesis test is descriptive.
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.5892 (MMRM model for inspiratory capacity with fixed effects of treatment, test day, treatment by test day interaction, baseline inspiratory capacity, baseline inspiratory capacity by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.027 · 95% CI -0.072 to 0.126This hypothesis test is descriptive.
SecondaryAdjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) on Day 1

Secondary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity on Day 1. Analysis of covariance model on log10 transformation data. Adjusted means are back transformed to report in original units. Standard errors (SEs) are calculated using the delta method.

Time frame:
1 day
Reported as:
Least squares mean · seconds
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) on Day 1
secondsPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) on Day 1478.59 ± 17.861527.69 ± 19.670538.76 ± 19.715
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · ANCOVA · p = 0.0245 (ANCOVA model for log10 (endurance time \[s\]) with categorical effects of treatment and (log10-transformed) baseline as continuous covariate.) · Treatment ratio: 1.126 · 95% CI 1.015 to 1.248This hypothesis test is descriptive.
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · ANCOVA · p = 0.0655 · Treatment ratio: 1.103 · 95% CI 0.994 to 1.223Descriptive
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · ANCOVA · p = 0.6912 · Treatment ratio: 1.021 · 95% CI 0.921 to 1.132Descriptive
SecondaryAdjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 6 Weeks Treatment

Secondary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment.The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.

Time frame:
6 weeks
Reported as:
Least squares mean · seconds
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 6 Weeks Treatment
secondsPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 6 Weeks Treatment427.74 ± 17.093522.26 ± 20.232525.62 ± 19.990
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.0002 (MMRM model for log10 (endurance time \[s\]) with fixed effects of treatment, test day, treatment by test day interaction, log10 (baseline endurance time \[s\]), log10 (baseline endurance time \[s\]) by test day interaction, patient as a random effect.) · Treatment ratio: 1.229 · 95% CI 1.103 to 1.370Mean and 95% confidence limits were transformed from log10 back to the original scale. SE was calculated using the delta method.
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = 0.0004 (MMRM model for log10 (endurance time \[s\]) with fixed effects of treatment, test day, treatment by test day interaction, log10 (baseline endurance time \[s\]), log10 (baseline endurance time \[s\]) by test day interaction, patient as a random effect.) · Treatment ratio: 1.221 · 95% CI 1.095 to 1.362Mean and 95% confidence limits were transformed from log10 back to the original scale. SE was calculated using the delta method.
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.9062 (MMRM model for log10 (endurance time \[s\]) with fixed effects of treatment, test day, treatment by test day interaction, log10 (baseline endurance time \[s\]), log10 (baseline endurance time \[s\]) by test day interaction, patient as a random effect.) · Treatment ratio: 1.006 · 95% CI 0.905 to 1.12Mean and 95% confidence limits were transformed from log10 back to the original scale. SE was calculated using the delta method.
SecondaryAdjusted Mean Inspiratory Capacity at Pre-exercise After 1 Day

Secondary endpoint was pre-exercise inspiratory capacity (IC) during constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) on Day 1.

Time frame:
1 day
Reported as:
Least squares mean · liters
Adjusted Mean Inspiratory Capacity at Pre-exercise After 1 Day
litersPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Inspiratory Capacity at Pre-exercise After 1 Day2.440 ± 0.0412.642 ± 0.0412.605 ± 0.041
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · ANCOVA · p = 0.0049 (ANCOVA model for inspiratory capacity (liters) with categorical effect of treatment and baseline as continuous covariate.) · Lsmean difference-final values: 0.165 · 95% CI 0.051 to 0.279Descriptive
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · ANCOVA · p = 0.0006 (ANCOVA model for inspiratory capacity (liters) with categorical effect of treatment and baseline as continuous covariate.) · Lsmean difference-final values: 0.202 · 95% CI 0.088 to 0.316Descriptive
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · ANCOVA · p = 0.5162 (ANCOVA model for inspiratory capacity (liters) with categorical effect of treatment and baseline as continuous covariate.) · Lsmean difference-final values: -0.037 · 95% CI -0.151 to 0.076Descriptive
SecondaryAdjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks

Secondary endpoint was pre-exercise inspiratory capacity (IC) during constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) after 6 weeks of treatment.

Time frame:
6 weeks
Reported as:
Least squares mean · liters
Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks
litersPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks2.402 ± 0.0372.589 ± 0.0362.627 ± 0.035
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = <0.0001 (MMRM model for inspiratory capacity with fixed effects of treatment, test day, treatment by test day interaction, baseline inspiratory capacity, baseline inspiratory capacity by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.225 · 95% CI 0.124 to 0.326Descriptive
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = 0.0003 (MMRM model for inspiratory capacity with fixed effects of treatment, test day, treatment by test day interaction, baseline inspiratory capacity, baseline inspiratory capacity by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.187 · 95% CI 0.086 to 0.288Descriptive
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.4541 (MMRM model for inspiratory capacity with fixed effects of treatment, test day, treatment by test day interaction, baseline inspiratory capacity, baseline inspiratory capacity by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.038 · 95% CI -0.061 to 0.137Descriptive
SecondaryAdjusted Mean Slope of the Intensity of Breathing Discomfort on Day 1

Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 1 day of treatment. The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates slowing down in decline in breathing, i.e., favorable results.

Time frame:
1 day
Reported as:
Least squares mean · units / seconds
Adjusted Mean Slope of the Intensity of Breathing Discomfort on Day 1
units / secondsPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Slope of the Intensity of Breathing Discomfort on Day 10.014 ± 0.0010.012 ± 0.0010.012 ± 0.001
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · ANCOVA · p = 0.0468 (ANCOVA model for mean slope of the intensity of breathing discomfort with categorical effect of treatment and baseline as continuous covariate.) · Lsmean difference-final values: -0.002 · 95% CI -0.004 to -0.000Descriptive
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · ANCOVA · p = 0.0180 (ANCOVA model for mean slope of the intensity of breathing discomfort with categorical effect of treatment and baseline as continuous covariate.) · Lsmean difference-final values: -0.002 · 95% CI -0.005 to -0.000Descriptive
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · ANCOVA · p = 0.6856 (ANCOVA model for mean slope of the intensity of breathing discomfort with categorical effect of treatment and baseline as continuous covariate.) · Lsmean difference-final values: 0.000 · 95% CI -0.002 to 0.002Descriptive
SecondaryAdjusted Mean Slope of the Intensity of Breathing Discomfort After Week 6

Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment. The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates favorable results.

Time frame:
6 weeks
Reported as:
Least squares mean · units / seconds
Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 6
units / secondsPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 60.016 ± 0.0010.013 ± 0.0010.013 ± 0.001
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.0081 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: -0.003 · 95% CI -0.005 to -0.001Descriptive
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = 0.0099 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: -0.003 · 95% CI -0.005 to -0.001Descriptive
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.9626 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: -0.000 · 95% CI -0.002 to 0.002Descriptive
SecondaryAdjusted Mean Slope of the Intensity of Breathing Discomfort After Week 12

Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 12 weeks of treatment. The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates favorable results.

Time frame:
12 weeks
Reported as:
Least squares mean · units / seconds
Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 12
units / secondsPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 120.015 ± 0.0010.013 ± 0.0010.013 ± 0.001
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.0598 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: -0.002 · 95% CI -0.004 to 0.000Descriptive
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = 0.0218 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: -0.003 · 95% CI -0.005 to -0.000Descriptive
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.6549 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.000 · 95% CI -0.002 to 0.003Descriptive
SecondaryAdjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) on Day 1

Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed on day 1

Time frame:
1 day
Reported as:
Least squares mean · liters
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) on Day 1
litersPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) on Day 11.509 ± 0.0201.693 ± 0.0191.679 ± 0.019
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = <0.0001 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.170 · 95% CI 0.116 to 0.224Descriptive
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = <0.0001 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.184 · 95% CI 0.129 to 0.239Descriptive
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.6105 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: -0.014 · 95% CI -0.067 to 0.040Descriptive
SecondaryAdjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 6 Weeks

Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 6 weeks of treatment

Time frame:
6 weeks
Reported as:
Least squares mean · liters
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 6 Weeks
litersPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 6 Weeks1.517 ± 0.0201.790 ± 0.0191.763 ± 0.019
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = <0.0001 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.246 · 95% CI 0.192 to 0.300Descriptive
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = <0.0001 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.273 · 95% CI 0.218 to 0.328Descriptive
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.3236 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: -0.027 · 95% CI -0.080 to 0.027Descriptive
SecondaryAdjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 12 Weeks

Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 12 weeks of treatment

Time frame:
12 weeks
Reported as:
Least squares mean · liters
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 12 Weeks
litersPlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µg
Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 12 Weeks1.527 ± 0.0201.784 ± 0.0191.778 ± 0.019
Statistical analysis
  • Placebo vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = <0.0001 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.251 · 95% CI 0.196 to 0.305Descriptive
  • Placebo vs Tio+Olo 2.5 / 5.0 µg · Mixed Models Analysis · p = <0.0001 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: 0.257 · 95% CI 0.202 to 0.312Descriptive
  • Tio+Olo 2.5 / 5.0 µg vs Tio+Olo 5.0 / 5.0 µg · Mixed Models Analysis · p = 0.8156 (MMRM model with fixed effects of treatment, test day, treatment by test day interaction, baseline, baseline by test day interaction, and patient as a random effect.) · Lsmean difference-final values: -0.006 · 95% CI -0.060 to 0.047Descriptive

Adverse events

Collected over 142 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—5/132 (3.8%)25/132 (18.9%)
Tio+Olo 2.5 / 5.0 μg—9/133 (6.8%)25/133 (18.8%)
Tio+Olo 5.0 / 5.0 μg—4/139 (2.9%)16/139 (11.5%)
Most frequent serious events
Showing 10 of 23
Most frequent serious events
EventPlaceboTio+Olo 2.5 / 5.0 μgTio+Olo 5.0 / 5.0 μg
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders2/1325/1330/139
PneumoniaInfections and infestations1/1321/1330/139
Invasive ductal breast carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/1320/1330/139
EpilepsyNervous system disorders1/1320/1330/139
DepressionPsychiatric disorders1/1320/1330/139
Cardio-respiratory arrestCardiac disorders0/1321/1330/139
Inguinal herniaGastrointestinal disorders0/1321/1330/139
Toxicity to various agentsInjury, poisoning and procedural complications0/1321/1330/139
Lung neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1321/1330/139
Malignant neoplasm of unknown primary siteNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1321/1330/139
Most frequent other events
Most frequent other events
EventPlaceboTio+Olo 2.5 / 5.0 μgTio+Olo 5.0 / 5.0 μg
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders15/13210/13310/139
NasopharyngitisInfections and infestations6/1329/1334/139
CoughRespiratory, thoracic and mediastinal disorders8/1329/1332/139

Baseline characteristics

Treated set included all randomised patients who were dispensed study medication and were documented to have taken any dose of study medication.

Age, Continuous
Age, Continuous(years)PlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µgTotal
Mean60.8 ± 7.661.9 ± 7.363.1 ± 7.562.0 ± 7.5
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboTio+Olo 2.5 / 5.0 µgTio+Olo 5.0 / 5.0 µgTotal
Female454644135
Male878795269
08

Study locations

60 sites
  • 1237.15.01503 Boehringer Ingelheim Investigational Site
    Torrance, California, United States
  • 1237.15.01512 Boehringer Ingelheim Investigational Site
    Hartford, Connecticut, United States
  • 1237.15.01506 Boehringer Ingelheim Investigational Site
    Springfield, Illinois, United States
  • 1237.15.01507 Boehringer Ingelheim Investigational Site
    Iowa City, Iowa, United States
  • 1237.15.01504 Boehringer Ingelheim Investigational Site
    Livonia, Michigan, United States
  • 1237.15.01511 Boehringer Ingelheim Investigational Site
    Saint Charles, Missouri, United States
  • 1237.15.01509 Boehringer Ingelheim Investigational Site
    Lebanon, New Hampshire, United States
  • 1237.15.01513 Boehringer Ingelheim Investigational Site
    Charlotte, North Carolina, United States
  • 1237.15.01514 Boehringer Ingelheim Investigational Site
    Philadelphia, Pennsylvania, United States
  • 1237.15.01516 Boehringer Ingelheim Investigational Site
    Pittsburgh, Pennsylvania, United States
  • 1237.15.01508 Boehringer Ingelheim Investigational Site
    Easley, South Carolina, United States
  • 1237.15.01501 Boehringer Ingelheim Investigational Site
    Greenville, South Carolina, United States
  • 1237.15.01505 Boehringer Ingelheim Investigational Site
    Spartanburg, South Carolina, United States
  • 1237.15.01502 Boehringer Ingelheim Investigational Site
    Union, South Carolina, United States
  • 1237.15.01510 Boehringer Ingelheim Investigational Site
    Richmond, Virginia, United States
  • 1237.15.54502 Boehringer Ingelheim Investigational Site
    Buenos Aires, Argentina
  • 1237.15.54501 Boehringer Ingelheim Investigational Site
    Mendonza, Argentina
  • 1237.15.54503 Boehringer Ingelheim Investigational Site
    Provincia de Buenos Aires, Argentina
  • 1237.15.11501 Boehringer Ingelheim Investigational Site
    Hamilotn, Ontario, Canada
  • 1237.15.11503 Boehringer Ingelheim Investigational Site
    Hamilton, Ontario, Canada
  • 1237.15.11504 Boehringer Ingelheim Investigational Site
    Kingston, Ontario, Canada
  • 1237.15.11505 Boehringer Ingelheim Investigational Site
    Montreal, Quebec, Canada
  • 1237.15.11502 Boehringer Ingelheim Investigational Site
    Ste-Foy, Quebec, Canada
  • 1237.15.35851 Boehringer Ingelheim Investigational Site
    Helsinki, Finland
  • 1237.15.35853 Boehringer Ingelheim Investigational Site
    Turku, Finland
  • 1237.15.35852 Boehringer Ingelheim Investigational Site
    Vaasa, Finland
  • 1237.15.33502 Boehringer Ingelheim Investigational Site
    Nîmes, France
  • 1237.15.33504 Boehringer Ingelheim Investigational Site
    Pessac, France
  • 1237.15.33501 Boehringer Ingelheim Investigational Site
    Strasbourg, France
  • 1237.15.49507 Boehringer Ingelheim Investigational Site
    Aschaffenburg, Germany
  • 1237.15.49502 Boehringer Ingelheim Investigational Site
    Berlin, Germany
  • 1237.15.49504 Boehringer Ingelheim Investigational Site
    Berlin, Germany
  • 1237.15.49501 Boehringer Ingelheim Investigational Site
    Großhansdorf, Germany
  • 1237.15.49509 Boehringer Ingelheim Investigational Site
    Hamburg, Germany
  • 1237.15.49505 Boehringer Ingelheim Investigational Site
    Hanover, Germany
  • 1237.15.49508 Boehringer Ingelheim Investigational Site
    Koblenz, Germany
  • 1237.15.49506 Boehringer Ingelheim Investigational Site
    Wiesloch, Germany
  • 1237.15.36504 Boehringer Ingelheim Investigational Site
    Budapest, Hungary
  • 1237.15.36501 Boehringer Ingelheim Investigational Site
    Deszk, Hungary
  • 1237.15.36503 Boehringer Ingelheim Investigational Site
    Nyíregyháza, Hungary
  • 1237.15.36502 Boehringer Ingelheim Investigational Site
    Pécs, Hungary
  • 1237.15.39512 Boehringer Ingelheim Investigational Site
    Ferrara, Italy
  • 1237.15.39504 Boehringer Ingelheim Investigational Site
    Parma, Italy
  • 1237.15.39503 Boehringer Ingelheim Investigational Site
    Pavia, Italy
  • 1237.15.39501 Boehringer Ingelheim Investigational Site
    Pisa, Italy
  • 1237.15.39509 Boehringer Ingelheim Investigational Site
    Pisa, Italy
  • 1237.15.39511 Boehringer Ingelheim Investigational Site
    Roma, Italy
  • 1237.15.39508 Boehringer Ingelheim Investigational Site
    Sesto San Giovanni (MI), Italy
  • 1237.15.39506 Boehringer Ingelheim Investigational Site
    Trieste, Italy
  • 1237.15.34506 Boehringer Ingelheim Investigational Site
    Alicante, Spain
  • 1237.15.34501 Boehringer Ingelheim Investigational Site
    Barakaldo (Bilbao), Spain
  • 1237.15.34507 Boehringer Ingelheim Investigational Site
    Madrid, Spain
  • 1237.15.34009 Boehringer Ingelheim Investigational Site
    Málaga, Spain
  • 1237.15.34001 Boehringer Ingelheim Investigational Site
    Santander, Spain
  • 1237.15.44152 Boehringer Ingelheim Investigational Site
    Leicester, United Kingdom
  • 1237.15.44154 Boehringer Ingelheim Investigational Site
    Liverpool, United Kingdom
  • 1237.15.44153 Boehringer Ingelheim Investigational Site
    London, United Kingdom
  • 1237.15.44151 Boehringer Ingelheim Investigational Site
    Manchester, United Kingdom
  • 1237.15.44155 Boehringer Ingelheim Investigational Site
    Norwich, United Kingdom
  • 1237.15.44158 Boehringer Ingelheim Investigational Site
    Plymouth, United Kingdom
09

References and documents

Publications

  • Maltais F, O'Donnell D, Galdiz Iturri JB, Kirsten AM, Singh D, Hamilton A, Tetzlaff K, Zhao Y, Casaburi R. Effect of 12 weeks of once-daily tiotropium/olodaterol on exercise endurance during constant work-rate cycling and endurance shuttle walking in chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2018 Jan-Dec;12:1753465818755091. doi: 10.1177/1753465818755091. PubMed 29439648 ↗

Related links

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 29, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01525615
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Feb 3, 2012
Start date
Feb 2012
Primary completion
Sep 2013
Completion
Sep 2013
Results posted
Sep 15, 2015
Last update
Aug 29, 2016

Study contacts

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

Not currently enrolling

This study is completed, as verified in Jul 2016. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Tiotropium · Olodaterol

Other studies in this condition

Pulmonary Disease, Chronic Obstructive →

Other studies from this sponsor

Boehringer Ingelheim →

Start the discussion