Characterization of 24-hour Lung Function Profiles of Inhaled Tiotropium + Olodaterol Fixed Dose Combination in Patients Suffering From Chronic Obstructive Pulmonary Disease

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

Randomised, Double-blind, Placebo-controlled, 6 Treatment, 4 Period, Incomplete Cross-over Trial to Characterise the 24-hour Lung Function Profiles of Tiotropium + Olodaterol Fixed Dose Combination (2.5/5 µg, 5/5 µg), Tiotropium (2.5 µg, 5 µg) and Olodaterol (5 µg) (Oral Inhalation, Delivered by the Respimat® Inhaler) After 6 Weeks Once Daily Treatment in Patients With Chronic Obstructive Pulmonary Disease (COPD) [VIVACITOTM]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01559116
• Other study ID #: 1237.20
• Secondary ID: 2011-004710-42
• Status: Completed
• Phase: Phase 3
• First received: March 19, 2012
• Last updated: June 19, 2015
• Start date: March 2012
• Est. completion date: August 2013

Study information

• Verified date: June 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Public Service Health, Food Chain Safety, EnvironmentCanada: Health CanadaDenmark: The Danish Health and Medicines AuthorityGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyNetherlands: Central Committee Research Involving Human SubjectsUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of the trial is to determine the 24-hour FEV1-time profile of tiotropium + olodaterol FDC, administered once daily by the RESPIMAT Inhaler after 6 weeks of treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 219
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion criteria:

1. Diagnosis of chronic obstructive pulmonary disease

2. Relatively stable airway obstruction with a post-bronchodilator FEV1< 80% of predicted normal and a post-bronchodilator FEV1/FVC <70%

3. Male or female patients, 40 years of age or older

4. Smoking history of more than 10 pack years

5. Ability to perform technically acceptable pulmonary function tests and maintain records

6. Ability to inhale medication in a competent manner from the RESPIMAT Inhaler and from a metered dose inhaler (MDI)

Exclusion criteria:

1. significant disease other than COPD

2. clinically relevant abnormal lab values

3. history of asthma

4. diagnosis of thyrotoxicosis

5. diagnosis of paroxysmal tachycardia

6. history of myocardial infarction

7. unstable or life-threatening cardiac arrhythmia

8. Hospitalization for heart failure within the past year

9. known active tuberculosis

10. malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years

11. history of life-threatening pulmonary obstruction

12. history of cystic fibrosis

13. clinically evident bronchiectasis

14. history of significant alcohol or drug abuse

15. history of thoracotomy with pulmonary resection

16. oral or patch ß-adrenergics

17. oral corticosteroid medication at unstable doses

18. regular use daytime oxygen therapy for more than one hour per day

19. Pulmonary rehabilitation program in the six weeks prior to the screening visit

20. Investigational drug within one month or six half lives (whichever is greater) prior to screening visit

21. Known hypersensitivity to ß-adrenergic drugs, BAC, EDTA

22. Pregnant or nursing women

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

24. Patients who have previously been randomised in this study or are currently participating in another study

25. Patients who are unable to comply with pulmonary medication restrictions prior to randomisation

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• tiotropium + olodaterol
low dose + one dose only
• tiotropium
low dose
• olodaterol
one dose only
• tiotropium
high dose
• tiotropium + olodaterol
low dose + one dose only
• Placebo
placebo matching tiotropium+olodaterol FDC

Device:
• Respimat
Respimat inhaler

Locations

Country	Name	City	State
Belgium	1237.20.32203 Boehringer Ingelheim Investigational Site	Genk
Belgium	1237.20.32201 Boehringer Ingelheim Investigational Site	Gent
Belgium	1237.20.32204 Boehringer Ingelheim Investigational Site	Jambes
Canada	1237.20.02202 Boehringer Ingelheim Investigational Site	Quebec
Canada	1237.20.02201 Boehringer Ingelheim Investigational Site	Sherbrooke	Quebec
Denmark	1237.20.45002 Boehringer Ingelheim Investigational Site	Hvidovre
Denmark	1237.20.45003 Boehringer Ingelheim Investigational Site	Odense C
Denmark	1237.20.45001 Boehringer Ingelheim Investigational Site	Silkeborg
Germany	1237.20.49205 Boehringer Ingelheim Investigational Site	Berlin
Germany	1237.20.49204 Boehringer Ingelheim Investigational Site	Großhansdorf
Germany	1237.20.49203 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1237.20.49206 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1237.20.49201 Boehringer Ingelheim Investigational Site	Mannheim
Germany	1237.20.49207 Boehringer Ingelheim Investigational Site	Mönchengladbach
Germany	1237.20.49202 Boehringer Ingelheim Investigational Site	Wiesbaden
Hungary	1237.20.36202 Boehringer Ingelheim Investigational Site	Gödöllö
Hungary	1237.20.36204 Boehringer Ingelheim Investigational Site	Komarom
Hungary	1237.20.36203 Boehringer Ingelheim Investigational Site	Pecs
Hungary	1237.20.36201 Boehringer Ingelheim Investigational Site	Szarvas
Hungary	1237.20.36205 Boehringer Ingelheim Investigational Site	Szazhalombatta
Netherlands	1237.20.31205 Boehringer Ingelheim Investigational Site	Almelo
Netherlands	1237.20.31202 Boehringer Ingelheim Investigational Site	Breda
Netherlands	1237.20.31201 Boehringer Ingelheim Investigational Site	Heerlen
Netherlands	1237.20.31204 Boehringer Ingelheim Investigational Site	Hengelo
Netherlands	1237.20.31203 Boehringer Ingelheim Investigational Site	Zutphen
United States	1237.20.1203 Boehringer Ingelheim Investigational Site	Easley	South Carolina
United States	1237.20.1201 Boehringer Ingelheim Investigational Site	Greenville	South Carolina
United States	1237.20.1204 Boehringer Ingelheim Investigational Site	Jasper	Alabama
United States	1237.20.1202 Boehringer Ingelheim Investigational Site	Spartanburg	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  Germany,  Hungary,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forced Expiratory Volume in 1 Second (FEV1) AUC0-24h Response [L] After 6 Weeks Treatment.	Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 0 to 24 h post-dose, using the trapezoidal rule, divided by the duration (24 h) to report in litres.; Mean is actually the Adjusted mean.; The adjusted mean and standard error (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day 1 and week 6	No
Secondary	FEV1 AUC0-12h Response [L] After 6 Weeks Treatment.	Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 0 to 12 h post-dose, using the trapezoidal rule, divided by the duration (12h) to report in litres.; Mean is actually the Adjusted mean.; The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day 1 and week 6	No
Secondary	FEV1 AUC12-24h Response [L] After 6 Weeks Treatment.	Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 12 to 24 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.; Mean is actually the Adjusted mean.; The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day 1 and week 6	No
Secondary	Trough FEV1 Response [L] After 6 Weeks Treatment.	Trough Forced Expiratory Volume in 1 second (FEV1) response after 6 weeks treatment period.; The trough was defined as the mean of the 23 h and 23 h50 min measurements and Response was defined as the change from patient baseline.; Mean is actually the Adjusted mean.; The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day 1 and week 6	No
Secondary	Peak(0-3h) FEV1 Response [L] After 6 Weeks Treatment.	Peak (0-3h) Forced Expiratory Volume in 1 second (FEV1) response.; The peak was defined as the maximum value measured within the first 3 h post dosing and response was defined as the change from patient baseline.; Mean is actually the Adjusted mean.; The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day 1 and week 6	No
Secondary	FVC AUC0-24h Response [L] After 6 Weeks Treatment.	Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres.; Mean is actually the Adjusted mean.; The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day 1 and week 6	No
Secondary	FVC AUC0-12h Response [L] After 6 Weeks Treatment.	Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.; Mean is actually the Adjusted mean.; The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day 1 and week 6	No
Secondary	FVC AUC12-24h Response [L] After 6 Weeks Treatment.	Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 12 to 24 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.; Mean is actually the Adjusted mean.; The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day 1 and week 6	No
Secondary	Trough FVC Response [L] After 6 Weeks Treatment.	Trough Forced Vital Capacity (FVC) response after 6 weeks treatment period.; The trough was defined as the mean of the 23 h and 23 h50 min measurements and response was defined as the change from patient baseline.; Mean is actually the Adjusted mean.; The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day1 and week 6	No
Secondary	Peak (0-3h) FVC Response [L] After 6 Weeks Treatment.	Peak (0-3h) Forced Vital Capacity (FVC) responses after 6 weeks treatment.; Peak was defined as the maximum value measured within the first 3 h post dosing and response was defined as the change from patient baseline.; Mean is actually the Adjusted mean.; The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom.	day 1 and week 6	No

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