Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2013-000808-41 | EudraCT Number | EudraCT |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| T+O FDC dosage 1 | Experimental | Low dose |
|
| T+O FDC dosage 2 | Experimental | High dose |
|
| ICS/LABA FDC Dosage 1 | Active Comparator | Low dose |
|
| ICS/LABA FDC Dosage 2 | Active Comparator | High dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fluticasone propionate | Drug | low dose |
| |
| salmeterol |
| 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. |
| 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. |
Not provided
Inclusion criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1237.11.32002 Boehringer Ingelheim Investigational Site | Genk | Belgium | ||||
| 1237.11.32001 Boehringer Ingelheim Investigational Site |
After signing informed consent, patients entered a 4-week screening period to ensure clinical stability (i.e. no exacerbations).
This was a randomized, double-blind, double-dummy, active-controlled, 4-treatment, 4-period, complete cross-over design.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | T+O 2.5/5 / T+O 5/5 / F+S 250/50 / F+S 500/50 | Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled .
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
|
| placebo | Drug | placebo/dummy for blinding purposes |
|
| placebo | Drug | placebo/dummy for blinding purposes |
|
| tiotropium | Drug | tiotropium high dose |
|
| olodaterol | Drug |
|
| olodaterol | Drug |
|
| placebo | Drug | placebo/dummy for blinding purposes |
|
| placebo | Drug | placebo/dummy for blinding purposes |
|
| tiotropium | Drug | tiotropium low dose |
|
| fluticasone propionate | Drug | low dose |
|
| salmeterol | Drug |
|
| 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. |
| Ghent |
| Belgium |
| 1237.11.42003 Boehringer Ingelheim Investigational Site | Kyjov | Czechia |
| 1237.11.42004 Boehringer Ingelheim Investigational Site | Rokycany | Czechia |
| 1237.11.42002 Boehringer Ingelheim Investigational Site | Tábor | Czechia |
| 1237.11.42001 Boehringer Ingelheim Investigational Site | Třebíč | Czechia |
| 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 | Denmark |
| 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 | Germany |
| 1237.11.36001 Boehringer Ingelheim Investigational Site | Debrecen | Hungary |
| 1237.11.36004 Boehringer Ingelheim Investigational Site | Pécs | Hungary |
| 1237.11.36003 Boehringer Ingelheim Investigational Site | Szeged | Hungary |
| 1237.11.36002 Boehringer Ingelheim Investigational Site | Szombathely | Hungary |
| 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 | Netherlands |
| 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 | Spain |
| 1237.11.46001 Boehringer Ingelheim Investigational Site | Lund | Sweden |
| FG001 | T+O 5/5 / F+S 500/50 / T+O 2.5/5 / F+S 250/50 | Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®. |
| FG002 | F+S 250/50 / T+O 2.5/5 / F+S 500/50 / T+O 5/5 | Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®. |
| FG003 | F+S 500/50 / F+S 250/50 / T+O 5/5 / T+O 2.5/5 | Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Treated Set: All randomised patients who received any dose of the trial medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study | Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 | 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. | FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint. | Posted | Mean | Standard Error | Litres | Baseline and 6 weeks. |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint. | Posted | Mean | Standard Error | Litres | Baseline and 6 weeks. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint. | Posted | Mean | Standard Error | Litres | Baseline and 6 weeks. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint. | Posted | Mean | Standard Error | Litres | Baseline and 6 weeks. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint. | Posted | Mean | Standard Error | Litres | Baseline and 6 weeks. |
|
From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | T+O 2.5/5 / F+S Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (T+O 2.5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®. | 6 | 215 | 21 | 215 | ||
| EG001 | T+O 5/5 / F+S Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg (T+O 5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®. | 7 | 221 | 28 | 221 | ||
| EG002 | F+S 250/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. | 4 | 212 | 19 | 212 | ||
| EG003 | F+S 500/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. | 9 | 219 | 24 | 219 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina pectoris | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Lobar pneumonia | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Sialoadenitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Fibula fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Vascular graft occlusion | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 17.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068298 | Fluticasone |
| D000068299 | Salmeterol Xinafoate |
| D000069447 | Tiotropium Bromide |
| C549647 | olodaterol |
| ID | Term |
|---|---|
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D000420 | Albuterol |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
Not provided
Not provided
Difference calculated as T+O 5/5 - F+S 250/50 adjusted mean FEV1 AUC 0-12h change from patient baseline (L) |
| No |
| Superiority or Other |
| Null hypothesis: Mean FEV1 AUC 0-12h change from patient baseline (Tiotropium + Olodaterol 5/5 µg) = Mean FEV1 AUC 0-12h change from patient baseline (Fluticasone propionate + Salmeterol 500/50 µg). Hypothesis was analysed using a restricted maximum likelihood-based mixed effect repeated measures model including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect. | Mixed Models Analysis | Compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom. | <0.0001 | p-value is not adjusted for multiple comparisons. A priori threshold for statistical significance is two-sided alpha=0.05. | Mean Difference (Net) | 0.129 | Standard Error of the Mean | 0.011 | 2-Sided | 95 | 0.107 | 0.150 | Difference calculated as T+O 5/5 - F+S 500/50 adjusted mean FEV1 AUC 0-12h change from patient baseline (L) | No | Superiority or Other |
| Null hypothesis: Mean FEV1 AUC 0-12h change from patient baseline (Tiotropium + Olodaterol 2.5/5 µg) = Mean FEV1 AUC 0-12h change from patient baseline (Fluticasone propionate + Salmeterol 250/50 µg). Hypothesis was analysed using a restricted maximum likelihood-based mixed effect repeated measures model including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect. | Mixed Models Analysis | Compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom. | <0.0001 | p-value is not adjusted for multiple comparisons. A priori threshold for statistical significance is two-sided alpha=0.05. | Mean Difference (Net) | 0.103 | Standard Error of the Mean | 0.011 | 95 | 0.081 | 0.124 | Difference calculated as T+O 2.5/5 - F+S 250/50 adjusted mean FEV1 AUC 0-12h change from patient baseline (L) | No | Superiority or Other |
| Null hypothesis: Mean FEV1 AUC 0-12h change from patient baseline (Tiotropium + Olodaterol 2.5/5 µg) = Mean FEV1 AUC 0-12h change from patient baseline (Fluticasone propionate + Salmeterol 500/50 µg). Hypothesis was analysed using a restricted maximum likelihood-based mixed effect repeated measures model including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect. | Mixed Models Analysis | Compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom. | <0.0001 | p-value is not adjusted for multiple comparisons. A priori threshold for statistical significance is two-sided alpha=0.05. | Mean Difference (Net) | 0.106 | Standard Error of the Mean | 0.011 | 2-Sided | 95 | 0.085 | 0.128 | Difference calculated as T+O 2.5/5 - F+S 500/50 adjusted mean FEV1 AUC 0-12h change from patient baseline (L) | No | Superiority or Other |
| OG002 | F+S 250/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. |
| OG003 | F+S 500/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. |
|
|
|
| OG002 | F+S 250/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. |
| OG003 | F+S 500/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. |
|
|
|
| OG002 | F+S 250/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. |
| OG003 | F+S 500/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. |
|
|
|
| OG002 | F+S 250/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. |
| OG003 | F+S 500/50 / T+O Placebo | Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. • Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler. |
|
|
|