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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002641-66 | EudraCT Number |
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The objectives of the study are to explore the effect of treatment with tiotropium + olodaterol fixed dose combination (FDC) compared to fluticasone propionate + salmeterol FDC on:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tiotropium/Olodaterol Fixed Dose Combination | Experimental |
| |
| Fluticasone Propionate + Salmeterol Fixed Dose Combination | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tiotropium | Drug | Fixed Dose Combination |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) in the 6th Week of Treatment | LVEDVI is normalised left ventricular end diastolic volume, divided by body surface area. Baseline was defined as the value obtained during the assessment performed in a week prior to Visit 2 (Day 1). The change from baseline was calculated as the value obtained in a week prior to Visits 3 and 4 (end of each treatment periods) minus the baseline value. | Baseline and 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Aortic Distensibility After 6 Weeks of Treatment | Change from baseline in aortic distensibility is presented. Aortic distensibility measurements as measure of arterial stiffness were derived from cine images acquired at end-expiration in planes perpendicular to the thoracic aorta at the level of the pulmonary artery (ascending and descending section of thoracic aorta), abdominal aorta, and perpendicularly to the main, right, and left pulmonary arteries. |
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Inclusion criteria:
Patients must have stable airway obstruction with a post-bronchodilator Forced Expiratory Volume in 1st second (FEV1) < 70% of predicted normal calculated with European Coal and Steel Community (ECSC) formulas, and a post-bronchodilator FEV1/Forced Vital Capacity (FVC)< 70% at Visit 1
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CIMS Studienzentrum Bamberg GmbH | Bamberg | 96049 | Germany | |||
| Klinische Forschung Berlin GbR |
All patients were screened for eligibility to participate in the trial. Patients attended specialist sites which would then ensured that all patients met all inclusion/exclusion criteria. Patients were not to be randomized to trial treatment if any one of the specific entry criteria were not met.
Randomised, double-blind, active-controlled, two-period cross-over study in patients with chronic obstructive pulmonary disease (COPD) to investigate effect of 6-week treatment of tiotropium + olodaterol fixed dose combination (FDC) with fluticasone propionate + salmeterol FDC orally inhaled by the Respimat® and Accuhaler® inhaler respectively.
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| ID | Title | Description |
|---|---|---|
| FG000 | FluticasonePropionate+SalmeterolFDC/ Tiotropium+OlodaterolFDC | Patients orally inhaled total 2 inhalations daily (one inhalation in the morning and evening) via Accuhaler® inhaler of 1000 microgram (μg) fluticasone propionate + 100 μg salmeterol dry powder for inhalation (F+S 1000/100) (500 μg / 50 μg per actuation) for 6-week treatment in period 1 and patients orally inhaled 2 inhalations once daily (in the morning) via Respimat® inhaler of 5 μg tiotropium + 5 μg olodaterol inhalation solution (T+O 5/5) (2.5 μg /2.5 μg per actuation) for 6-weeks treatment in period 2. There was no washout between treatments. |
| FG001 | Tiotropium+OlodaterolFDC/ FluticasonePropionate+SalmeterolFDC | Patients orally inhaled 2 inhalations once daily (in the morning) via Respimat® inhaler of 5 μg tiotropium + 5 μg olodaterol inhalation solution (T+O 5/5) (2.5 μg /2.5 μg per actuation) for 6-week treatment in period 1 and patients orally inhaled total 2 inhalations daily (one inhalation in the morning and evening) via Accuhaler® inhaler of 1000 microgram (μg) fluticasone propionate + 100 μg salmeterol dry powder for inhalation (F+S 1000/100) (500 μg / 50 μg per actuation) for 6-weeks treatment in period 2. There was no washout between treatments. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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The treated set (TS): TS is nested within the randomised set and includes all patients who were dispensed study medication and were documented to have taken any dose of study medication. RS includes all patients who signed informed consent form and were also randomised, regardless whether the patient was treated with study medication or not.
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| ID | Title | Description |
|---|---|---|
| BG000 | Total Patients | Patients orally inhaled total 2 inhalations daily (one inhalation in the morning and evening) via Accuhaler® inhaler of 1000 microgram (μg) fluticasone propionate + 100 μg salmeterol dry powder for inhalation (F+S 1000/100) (500 μg / 50 μg per actuation) or orally inhaled 2 inhalations once daily (in the morning) via Respimat® inhaler of 5 μg tiotropium + 5 μg olodaterol inhalation solution (T+O 5/5) (2.5 μg /2.5 μg per actuation). Patients were randomly assigned to a treatment sequence in two 6-week periods. There was no washout between treatments. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) in the 6th Week of Treatment | LVEDVI is normalised left ventricular end diastolic volume, divided by body surface area. Baseline was defined as the value obtained during the assessment performed in a week prior to Visit 2 (Day 1). The change from baseline was calculated as the value obtained in a week prior to Visits 3 and 4 (end of each treatment periods) minus the baseline value. | FullAnalysisSet (FAS)ExcludingExacerbation (FAS-EE) nested within FAS and data from patients who had an exacerbation during treatments were excluded from this set. FAS nested within treated set and included patients who had baseline measurement and at least one post-baseline measurement for primary or secondary endpoints. (Including available data) | Posted | Least Squares Mean | Standard Error | Millilitre/ meter^2 (mL/m^2) | Baseline and 6 weeks |
|
From first drug administration until 21 days after last drug administration, up to 106 days.
Participant flow is presented by treatment sequence whereas adverse events (AEs) are presented by treatments arms and hence the number of participant differs from the number of participant assigned in participant flow. TS was used for AEs. TS is nested within the randomised set and includes all patients who were dispensed study medication and were documented to have taken any dose of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Fluticasone Propionate + Salmeterol FDC (F+S 1000/100) | Patients orally inhaled total 2 inhalations daily (one inhalation in the morning and evening) via Accuhaler® inhaler of 1000 microgram (μg) fluticasone propionate + 100 μg salmeterol dry powder for inhalation (F+S 1000/100) (500 μg / 50 μg per actuation) for 6-week treatment period. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ligament rupture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Centre | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 13, 2018 | Mar 20, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Nov 30, 2017 | Mar 20, 2019 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| D000069447 | Tiotropium Bromide |
| C549647 | olodaterol |
| D000068298 | Fluticasone |
| D000068299 | Salmeterol Xinafoate |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
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| Olodaterol | Drug | Fixed Dose Combination |
|
|
| Fluticasone propionate | Drug | Fixed Dose Combination |
|
| Salmeterol | Drug | Fixed Dose Combination |
|
| Baseline and 6 weeks |
| Change From Baseline in Pulmonary Artery Pulsatility After 6 Weeks of Treatment | Change from baseline in pulmonary artery pulsatility (PAP) is presented. Pulmonary artery pulsatility measurements as measure of arterial stiffness were derived from cine images acquired at end-expiration in planes perpendicular to the thoracic aorta at the level of the pulmonary artery (ascending and descending section of thoracic aorta), abdominal aorta, and perpendicularly to the main, right, and left pulmonary arteries. | Baseline and 6 weeks |
| Change From Baseline in Central Systolic Pressure After 6 Weeks of Treatment | Change from baseline in central systolic pressure is presented. | Baseline and 6 weeks |
| Change From Baseline in Pulse Pressure After 6 Weeks of Treatment | Change from baseline in pulse pressure is presented. | Baseline and 6 weeks |
| Change From Baseline in Aortic Augmentation Index After 6 Weeks of Treatment | Change from baseline in aortic augmentation index is presented. Augmentation index was derived from brachial pulse wave separation analysis as augmentation pressure (pressure difference between the reflection wave to the ejection wave) divided by central pulse pressure (at the central aortic site) multiplied by 100. | Baseline and 6 weeks |
| Change From Baseline in Functional Residual Capacity Body Plethysmography (FRCpleth) % Predicted After 6 Weeks of Treatment | Change from Baseline in Functional Residual Capacity Body Plethysmography (FRCpleth) % predicted is presented. Functional residual capacity, percent predicted is a lung volume at the end of normal expiration assessed/measured by body plethysmography and compared to predicted capacity for such subject, if nonsmoker and without a disease which could compromise their ventilator function, to give a percentage predicted. | Baseline and 6 weeks |
| Change From Baseline in 1.5 Hour Post Dose Forced Expiratory Volume in 1st Second (FEV1) After 6 Weeks of Treatment | Change from baseline in 1.5 hour post dose Forced Expiratory Volume in 1st second (FEV1) is presented. | Baseline and 6 weeks |
| Change From Baseline in 1.5 Hour Post Dose Forced Vital Capacity (FVC) After 6 Weeks of Treatment | Change from baseline in 1.5 hour post dose Forced Vital Capacity (FVC) is presented. | Baseline and 6 weeks |
| Berlin |
| 10787 |
| Germany |
| Universitätsklinikum Bonn AöR | Bonn | 53105 | Germany |
| Praxis Dr. med. Claus Keller | Frankfurt | 60389 | Germany |
| IKF Pneumologie GmbH & Co. KG | Frankfurt | 60596 | Germany |
| Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH | Großhansdorf | 22927 | Germany |
| Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg | Heidelberg | 69126 | Germany |
| KLB Gesundheitsforschung Lübeck GmbH | Lübeck | 23552 | Germany |
| Universitätsmedizin der Johannes Gutenberg-Universität Mainz | Mainz | 55131 | Germany |
| RoMed Kliniken | Rosenheim | 83022 | Germany |
| Withdrawal by Subject |
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| NOT COMPLETED |
|
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Patients orally inhaled total 2 inhalations daily (one inhalation in the morning and evening) via Accuhaler® inhaler of 1000 microgram (μg) fluticasone propionate + 100 μg salmeterol dry powder for inhalation (F+S 1000/100) (500 μg / 50 μg per actuation) for 6-week treatment period. |
| OG001 | Tiotropium + Olodaterol FDC (T+O 5/5) | Patients orally inhaled 2 inhalations once daily (in the morning) via Respimat® inhaler of 5 μg tiotropium + 5 μg olodaterol inhalation solution (T+O 5/5) (2.5 μg /2.5 μg per actuation) for 6-week treatment period. |
|
|
|
| Secondary | Change From Baseline in Aortic Distensibility After 6 Weeks of Treatment | Change from baseline in aortic distensibility is presented. Aortic distensibility measurements as measure of arterial stiffness were derived from cine images acquired at end-expiration in planes perpendicular to the thoracic aorta at the level of the pulmonary artery (ascending and descending section of thoracic aorta), abdominal aorta, and perpendicularly to the main, right, and left pulmonary arteries. | FAS-EE set including participants with available data for change from baseline in aortic distensibility. | Posted | Least Squares Mean | Standard Error | Percentage/millimeter of mercury(%/mmHg) | Baseline and 6 weeks |
|
|
|
|
| Secondary | Change From Baseline in Pulmonary Artery Pulsatility After 6 Weeks of Treatment | Change from baseline in pulmonary artery pulsatility (PAP) is presented. Pulmonary artery pulsatility measurements as measure of arterial stiffness were derived from cine images acquired at end-expiration in planes perpendicular to the thoracic aorta at the level of the pulmonary artery (ascending and descending section of thoracic aorta), abdominal aorta, and perpendicularly to the main, right, and left pulmonary arteries. | FAS-EE set including participants with available data for change from baseline in pulmonary artery pulsatility. | Posted | Least Squares Mean | Standard Error | Percentage of PAP (%) | Baseline and 6 weeks |
|
|
|
|
| Secondary | Change From Baseline in Central Systolic Pressure After 6 Weeks of Treatment | Change from baseline in central systolic pressure is presented. | FAS-EE set including participants with available data for change from baseline in central systolic pressure. | Posted | Least Squares Mean | Standard Error | mmHg | Baseline and 6 weeks |
|
|
|
|
| Secondary | Change From Baseline in Pulse Pressure After 6 Weeks of Treatment | Change from baseline in pulse pressure is presented. | FAS-EE set including participants with available data for change from baseline in pulse pressure. | Posted | Least Squares Mean | Standard Error | mmHg | Baseline and 6 weeks |
|
|
|
|
| Secondary | Change From Baseline in Aortic Augmentation Index After 6 Weeks of Treatment | Change from baseline in aortic augmentation index is presented. Augmentation index was derived from brachial pulse wave separation analysis as augmentation pressure (pressure difference between the reflection wave to the ejection wave) divided by central pulse pressure (at the central aortic site) multiplied by 100. | FAS-EE set including participants with available data for change from baseline in aortic augmentation index. | Posted | Least Squares Mean | Standard Error | Percentage of index (%) | Baseline and 6 weeks |
|
|
|
|
| Secondary | Change From Baseline in Functional Residual Capacity Body Plethysmography (FRCpleth) % Predicted After 6 Weeks of Treatment | Change from Baseline in Functional Residual Capacity Body Plethysmography (FRCpleth) % predicted is presented. Functional residual capacity, percent predicted is a lung volume at the end of normal expiration assessed/measured by body plethysmography and compared to predicted capacity for such subject, if nonsmoker and without a disease which could compromise their ventilator function, to give a percentage predicted. | FAS-EE set including participants with available data for change from baseline in FRCpleth. | Posted | Least Squares Mean | Standard Error | Percentage of FRCpleth (%) | Baseline and 6 weeks |
|
|
|
|
| Secondary | Change From Baseline in 1.5 Hour Post Dose Forced Expiratory Volume in 1st Second (FEV1) After 6 Weeks of Treatment | Change from baseline in 1.5 hour post dose Forced Expiratory Volume in 1st second (FEV1) is presented. | FAS-EE set including participants with available data for change from baseline in FEV1. | Posted | Least Squares Mean | Standard Error | Litre (L) | Baseline and 6 weeks |
|
|
|
|
| Secondary | Change From Baseline in 1.5 Hour Post Dose Forced Vital Capacity (FVC) After 6 Weeks of Treatment | Change from baseline in 1.5 hour post dose Forced Vital Capacity (FVC) is presented. | FAS-EE set including participants with available data for change from baseline in FVC. | Posted | Least Squares Mean | Standard Error | Litre (L) | Baseline and 6 weeks |
|
|
|
|
| 0 |
| 70 |
| 0 |
| 70 |
| 7 |
| 70 |
| EG001 | Tiotropium + Olodaterol FDC (T+O 5/5) | Patients orally inhaled 2 inhalations once daily (in the morning) via Respimat® inhaler of 5 μg tiotropium + 5 μg olodaterol inhalation solution (T+O 5/5) (2.5 μg /2.5 μg per actuation) for 6-week treatment period. | 0 | 74 | 2 | 74 | 13 | 74 |
| Osteoporotic fracture | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009930 |
| Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D000420 | Albuterol |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |