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

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)

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: salmeterol; Drug: placebo; Drug: tiotropium; Drug: olodaterol; Drug: tiotropium; Drug: fluticasone propionate

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T+O FDC dosage 1; Low dose	Drug: placebo; placebo/dummy for blinding purposes; Drug: tiotropium; tiotropium high dose; Drug: olodaterol; Drug: tiotropium; tiotropium low dose
Experimental: T+O FDC dosage 2; High dose	Drug: placebo; placebo/dummy for blinding purposes; Drug: tiotropium; tiotropium high dose; Drug: olodaterol; Drug: tiotropium; tiotropium low dose
Active Comparator: ICS/LABA FDC Dosage 1; Low dose	Drug: salmeterol; Drug: placebo; placebo/dummy for blinding purposes; Drug: fluticasone propionate; low dose
Active Comparator: ICS/LABA FDC Dosage 2; High dose	Drug: salmeterol; Drug: placebo; placebo/dummy for blinding purposes; Drug: fluticasone propionate; low dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: October 22, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimate): October 25, 2013

Study Record Updates

• Last Update Posted (Estimate): February 12, 2016
• Last Update Submitted That Met QC Criteria: January 14, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Xhance; Salmeterol Xinafoate; Tiotropium Bromide; Olodaterol
• Other Study ID Numbers: 1237.11; 2013-000808-41 (EudraCT Number: EudraCT)