Characterization of Lung Function Profile of Inhaled Tiotropium + Olodaterol Fixed Dose Combination Compared to Fluticasone Propionate + Salmeterol Fixed Dose Combination in COPD Patients

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

Randomized, Double-blind, Double-dummy, Active-controlled, 4 Period Complete Cross-over Study to Compare the Effect on Lung Function of 6 Weeks Once Daily Treatment With Orally Inhaled Tiotropium+Olodaterol Fixed Dose Combination Delivered by the Respimat® Inhaler vs. 6 Weeks Twice Daily Treatment With Fluticasone Propionate+Salmeterol Fixed Dose Combination Delivered by the Accuhaler® in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01969721
• Other study ID #: 1237.11
• Secondary ID: 2013-000808-41
• Status: Completed
• Phase: Phase 3
• First received: October 22, 2013
• Last updated: January 14, 2016
• Start date: October 2013
• Est. completion date: February 2015

Study information

• Verified date: January 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Public Service Health, Food Chain Safety, EnvironmentCzech Republic: State Institute for Drug ControlDenmark: The Danish Health and Medicines AuthorityGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyNetherlands: Central Committee Research Involving Human SubjectsSpain: Spanish Agency of MedicinesSweden: Medical Products AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of the trial is to compare the lung function profile of once daily treatment with tiotropium+olodaterol FDC [2.5/ 5µg and 5/ 5µg] delivered by the RESPIMAT with the lung function profile of twice daily treatment with fluticasone propionate+salmeterol FDC [250/50µg and 500/50µg] delivered by the Accuhaler® after 6 weeks of treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 229
• Est. completion date: February 2015
• Est. primary completion date: January 2015
• 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 30% </= Forced Expiratory Volume in 1 second (FEV1)<80% of predicted normal and a post-bronchodilator FEV1/(Forced Vital Capacity)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, Accuhaler and from a metered dose inhaler (MDI)

Exclusion criteria:

1. Significant disease other than COPD

2. COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or iv) or hospitalization in the last 3 months.

3. Clinically relevant abnormal lab values

4. History of asthma

5. Diagnosis of thyrotoxicosis

6. Diagnosis of paroxysmal tachycardia

7. History of myocardial infarction

8. Unstable or life-threatening cardiac arrhythmia

9. Hospitalization for heart failure within the past year

10. Known active tuberculosis

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

12. History of life-threatening pulmonary obstruction

13. History of cystic fibrosis

14. Clinically evident bronchiectasis

15. History of significant alcohol or drug abuse

16. History of thoracotomy with pulmonary resection

17. oral or patch ß-adrenergics

18. Oral corticosteroid medication within 6 weeks prior to Visit 1

19. Regular use daytime oxygen therapy for more than one hour per day

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

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

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

23. Pregnant or nursing women

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
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• fluticasone propionate
low dose
• salmeterol

• placebo
placebo/dummy for blinding purposes
• placebo
placebo/dummy for blinding purposes
• tiotropium
tiotropium high dose
• olodaterol

• olodaterol

• placebo
placebo/dummy for blinding purposes
• placebo
placebo/dummy for blinding purposes
• tiotropium
tiotropium low dose
• fluticasone propionate
low dose
• salmeterol

Locations

Country	Name	City	State
Belgium	1237.11.32002 Boehringer Ingelheim Investigational Site	Genk
Belgium	1237.11.32001 Boehringer Ingelheim Investigational Site	Gent
Czech Republic	1237.11.42003 Boehringer Ingelheim Investigational Site	Kyjov
Czech Republic	1237.11.42004 Boehringer Ingelheim Investigational Site	Rokycany
Czech Republic	1237.11.42002 Boehringer Ingelheim Investigational Site	Tabor
Czech Republic	1237.11.42001 Boehringer Ingelheim Investigational Site	Trebic
Denmark	1237.11.45002 Boehringer Ingelheim Investigational Site	Hvidovre
Denmark	1237.11.45004 Boehringer Ingelheim Investigational Site	Kolding
Denmark	1237.11.45001 Boehringer Ingelheim Investigational Site	Odense C
Denmark	1237.11.45003 Boehringer Ingelheim Investigational Site	Silkeborg
Germany	1237.11.49003 Boehringer Ingelheim Investigational Site	Großhansdorf
Germany	1237.11.49005 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1237.11.49001 Boehringer Ingelheim Investigational Site	Mannheim
Germany	1237.11.49004 Boehringer Ingelheim Investigational Site	Mönchengladbach
Germany	1237.11.49002 Boehringer Ingelheim Investigational Site	Wiesbaden
Hungary	1237.11.36001 Boehringer Ingelheim Investigational Site	Debrecen
Hungary	1237.11.36004 Boehringer Ingelheim Investigational Site	Pecs
Hungary	1237.11.36003 Boehringer Ingelheim Investigational Site	Szeged
Hungary	1237.11.36002 Boehringer Ingelheim Investigational Site	Szombathely
Netherlands	1237.11.31005 Boehringer Ingelheim Investigational Site	Almelo
Netherlands	1237.11.31002 Boehringer Ingelheim Investigational Site	Breda
Netherlands	1237.11.31006 Boehringer Ingelheim Investigational Site	Eindhoven
Netherlands	1237.11.31001 Boehringer Ingelheim Investigational Site	Heerlen
Netherlands	1237.11.31007 Boehringer Ingelheim Investigational Site	Hoorn
Netherlands	1237.11.31003 Boehringer Ingelheim Investigational Site	Zutphen
Spain	1237.11.34003 Boehringer Ingelheim Investigational Site	Alicante
Spain	1237.11.34001 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1237.11.34002 Boehringer Ingelheim Investigational Site	Pozuelo de Alarcón
Sweden	1237.11.46001 Boehringer Ingelheim Investigational Site	Lund

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Belgium,  Czech Republic,  Denmark,  Germany,  Hungary,  Netherlands,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FEV1 AUC (0-12h) Change From Patient Baseline After 6 Weeks of Treatment	Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 0 to 12hours post-dose (AUC 0-12h) [L] after 6 weeks of treatment. Measured values presented are actually adjusted means.; The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient.	Baseline and 6 weeks.	No
Secondary	FEV1 AUC (0-24h) Change From Patient Baseline After 6 Weeks of Treatment	Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 0 to 24 hours post-dose (AUC 0-24h) [L] after 6 weeks of treatment.; Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient.	Baseline and 6 weeks.	No
Secondary	Trough FEV1 Change From Patient Baseline After 6 Weeks of Treatment	Change from patient baseline in Trough Forced Expiratory Volume in one second (FEV1) after 6 weeks of treatment. Trough FEV1 was defined as the mean of the 23h and 23h 50min (minutes) post-dose FEV1 measurements. Measured values presented are actually adjusted means.; The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient.	Baseline and 6 weeks.	No
Secondary	FEV1 AUC (12-24h) Change From Patient Baseline After 6 Weeks of Treatment	Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 12 to 24 hours post-dose (AUC 12-24h) [L] after 6 weeks of treatment. Measured values presented are actually adjusted means.; The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient.	Baseline and 6 weeks.	No
Secondary	FEV1 Peak (0-3h) Change From Patient Baseline After 6 Weeks of Treatment	Change from patient baseline in Forced Expiratory Volume in one second (FEV1) peak (0-3 hours) after 6 weeks of treatment. FEV1 peak (0-3 hours) was defined as the maximum FEV1 value measured within the first three hours post dosing. Measured values presented are actually adjusted means.	Baseline and 6 weeks.	No

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