Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
This is a 4-week, multicenter, randomized, double-blind, parallel group and active controlled study. Patients will be randomized (1 to 1 ratio) to a 4-week double-blind treatment period of either FDC (fixed-dose combination) of tiotropium + olodaterol (5/5 µg) plus placebo or the free combination of tiotropium 5 µg and olodaterol 5 µg; all administered via the Respimat® inhaler. The purpose is to show non-inferiority between the FDC and the free combination of tiotropium and olodaterol in patients with COPD.
Interventions
DRUGFDC of tiotropium + olodaterol
Fixed Dose Combination of tiotropium + olodaterol
DRUGPlacebo
DRUGTiotropium
DRUGOlodaterol
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients. * Patients 40 years of age or older. * Patients with a smoking history \> 10 pack years. * Diagnostic of COPD with Post-bronchodilator FEV1 (Forced Expiratory Volume in one second) \>= 30% and \<80% of predicted normal and Post-bronchodilator FEV1/FVC (Forced Vital Capacity) \<70% at screening. * Symptomatic patients with CAT (COPD Assessment Test TM) score \>= 10 at screening. * Further inclusion criteria apply.
Exclusion criteria
* COPD exacerbation or symptoms of lower respiratory tract infection within 6 weeks prior to screening. * Patients with a current diagnosis of asthma. * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in 1 Second (FEV1) (in Liter) After 28 Days of Treatment | Day 29 | This outcome measure presents FEV1 after 28 days of treatment (measurement on Day 29). Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), and was measured at 24 hours (+/- 10 minutes) after trial medication administration at Visit 5. The FEV1 measurement at Visit 4, which was 24 hours after the last open-label run-in treatment intake and 15 minutes before the first double-blind study drug intake was the baseline measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Vital Capacity (FVC) (in Liter) After 28 Days of Treatment | Day 29 | This outcome measure presents trough FVC after 28 days of treatment (measurement on Day 29). The FVC measurement at Visit 4, which was 24 hours after the last open-label run-in treatment intake and 15 minutes before the first double-blind study drug intake was the baseline measurement for FVC. |
| Chronic Obstructive Pulmonary Disease (COPD) Assessment Test™ (CAT) Score on Day 28 | Day 28 | This outcome measure presents COPD assessment test score on Day 28. The COPD Assessment Test™ is a short 8-item questionnaire for assessment and monitoring of COPD health status in routine practice. Its scale is 0-40 (high score = poor health). The CAT measurement on Visit 4 prior to the first dose of double-blind study drug was the baseline for CAT. |
Countries
Austria, Denmark, Finland, France, Slovenia
Participant flow
Recruitment details
Definition: Open-Label Treated Set (OLTS): This patient set includes all patients who signed the informed consent and were dispensed open-label study medication during the run-in period prior to randomisation and were documented to have taken any dose of this medication.
Pre-assignment details
Definition: Randomised Set (RS): This patient set is nested within the OLTS and includes all patients who signed the informed consent form and were also randomised, regardless of whether the patient was treated with study medication or not.
Participants by arm
| Arm | Count |
|---|---|
| T+O 5/5 The subjects were administered Tiotropium (T) + Olodaterol (O) Fixed Dose Combination (FDC) solution for inhalation 2.5 μg/2.5 μg per actuation, 2 inhalations orally once daily via RESPIMAT® inhaler.
Placebo matching Tiotropium solution was administered 2 inhalations once daily via RESPIMAT® inhaler. | 110 |
| T 5/O 5 The subjects were administered Tiotropium solution for inhalation, 2.5 μg per actuation + Olodaterol solution for inhalation, 2.5 μg per actuation as a free combination. Two inhalations were administered once daily (a.m. dosing) via RESPIMAT® inhaler for both Tiotropium and Olodaterol. | 111 |
| Total | 221 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | T+O 5/5 | T 5/O 5 | Total |
|---|---|---|---|
| Age, Continuous | 66.5 Years STANDARD_DEVIATION 7.1 | 66.5 Years STANDARD_DEVIATION 6.4 | 66.5 Years STANDARD_DEVIATION 6.8 |
| Sex: Female, Male Female | 33 Participants | 30 Participants | 63 Participants |
| Sex: Female, Male Male | 77 Participants | 81 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 110 | 9 / 111 | 18 / 221 |
| serious Total, serious adverse events | 1 / 110 | 2 / 111 | 3 / 221 |
Outcome results
Primary
Trough Forced Expiratory Volume in 1 Second (FEV1) (in Liter) After 28 Days of Treatment
This outcome measure presents FEV1 after 28 days of treatment (measurement on Day 29). Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), and was measured at 24 hours (+/- 10 minutes) after trial medication administration at Visit 5. The FEV1 measurement at Visit 4, which was 24 hours after the last open-label run-in treatment intake and 15 minutes before the first double-blind study drug intake was the baseline measurement.
Time frame: Day 29
Population: Full Analysis Set (FAS): This patient set is nested within the TS and includes patients who had a baseline measurement and at least one post-baseline measurement for the primary endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| T+O 5/5 | Trough Forced Expiratory Volume in 1 Second (FEV1) (in Liter) After 28 Days of Treatment | 1.422 Liter | Standard Error 0.016 |
| T 5/O 5 | Trough Forced Expiratory Volume in 1 Second (FEV1) (in Liter) After 28 Days of Treatment | 1.399 Liter | Standard Error 0.016 |
Comparison: The primary analysis was conducted using an Analysis of Covariance \[ANCOVA\] model including treatment as fixed categorical effect and baseline as continuous covariate.p-value: <0.000195% CI: [-0.02, 0.067]ANCOVA
Secondary
Chronic Obstructive Pulmonary Disease (COPD) Assessment Test™ (CAT) Score on Day 28
This outcome measure presents COPD assessment test score on Day 28. The COPD Assessment Test™ is a short 8-item questionnaire for assessment and monitoring of COPD health status in routine practice. Its scale is 0-40 (high score = poor health). The CAT measurement on Visit 4 prior to the first dose of double-blind study drug was the baseline for CAT.
Time frame: Day 28
Population: FAS. One patient in the T 5/O 5 free combination group had missing data for the CAT questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| T+O 5/5 | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test™ (CAT) Score on Day 28 | 15.423 Score on scale | Standard Error 0.377 |
| T 5/O 5 | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test™ (CAT) Score on Day 28 | 15.750 Score on scale | Standard Error 0.379 |
Comparison: The secondary analysis was conducted using an ANCOVA model including treatment as fixed categorical effect and baseline as continuous covariate.p-value: 0.54295% CI: [-1.384, 0.729]ANCOVA
Secondary
Trough Forced Vital Capacity (FVC) (in Liter) After 28 Days of Treatment
This outcome measure presents trough FVC after 28 days of treatment (measurement on Day 29). The FVC measurement at Visit 4, which was 24 hours after the last open-label run-in treatment intake and 15 minutes before the first double-blind study drug intake was the baseline measurement for FVC.
Time frame: Day 29
Population: FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| T+O 5/5 | Trough Forced Vital Capacity (FVC) (in Liter) After 28 Days of Treatment | 3.126 Liter | Standard Error 0.024 |
| T 5/O 5 | Trough Forced Vital Capacity (FVC) (in Liter) After 28 Days of Treatment | 3.121 Liter | Standard Error 0.024 |
Comparison: The secondary analysis was conducted using an ANCOVA model including treatment as fixed categorical effect and baseline as continuous covariate.p-value: 0.864895% CI: [-0.061, 0.073]ANCOVA