Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The primary objective of this study is to assess the safety of 52 weeks once daily treatment with orally inhaled tiotropium + olodaterol FDC and olodaterol (delivered by the RESPIMAT Inhaler) in Japanese patients with Chronic Obstructive Pulmonary Disease (COPD).
Interventions
Tiotropium and Olodaterol FDC once daily inhalation
DEVICERespimat
Respimat inhaler
DRUGOlodaterol
Olodaterol once daily inhalation
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of chronic obstructive pulmonary disease. 2. Relatively stable airway obstruction with post FEV1\< 80% predicted normal and post FEV1/FVC \<70%. 3. Male or female Japanese patients, 40 years of age or older. 4. Smoking history of more than 10 pack years.
Exclusion criteria
1. Significant disease other than COPD 2. Clinically relevant abnormal lab values. 3. History of asthma. 4. Diagnosis of thyrotoxicosis 5. Diagnosis of paroxysmal tachycardia 6. History of myocardial infarction within 1 year of screening visit 7. Unstable or life-threatening cardiac arrhythmia. 8. Hospitalization for heart failure within the past year. 9. Known active tuberculosis. 10. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years 11. History of life-threatening pulmonary obstruction. 12. History of cystic fibrosis. 13. Clinically evident bronchiectasis. 14. History of significant alcohol or drug abuse. 15. Thoracotomy with pulmonary resection 16. Oral ß-adrenergics. 17. Oral corticosteroid medication at unstable doses 18. Regular use of daytime oxygen therapy for more than one hour per day 19. Pulmonary rehabilitation program in the six weeks prior to the screening visit 20. Investigational drug within one month or six half lives (whichever is greater) prior to screening visit 21. Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA 22. Pregnant or nursing women. 23. Women of childbearing potential not using a highly effective method of birth control 24. Patients who are unable to comply with pulmonary medication restrictions 25. Patients with narrow-angle glaucoma or micturition disorder due to prostatic hyperplasia etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number (%) of Patients With Drug-related AEs | From first drug administration until 21 days after the last administration, upto 392 days | Number (%) of patients with drug-related Adverse Events (AEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 AUC0-3h Response | Baseline and 1 h, 10 min pre-dose and 30 min, 1 h, 2 h, 3 h post-dose after 52 weeks | Forced Expiratory Volume in 1 second Area Under Curve (AUC0-3h) response. FEV1 AUC0-3h was calculated using the trapezoidal rule, divided by the duration (3 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. Note: The Mean presented is the unadjusted mean. |
| Trough FEV1 Response | Baseline and 1 h, 10 min pre-dose after 52 weeks | Trough Forced Expiratory Volume in 1 second Response. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements after 52 weeks. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. Note: The Mean presented is the unadjusted mean. |
Countries
Japan
Participant flow
Pre-assignment details
This study was a 52-week multi-centre, randomised, double-blind and parallel-group design.
Participants by arm
| Arm | Count |
|---|---|
| Olodaterol (5 μg) Olodaterol solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period. | 41 |
| Tiotropium + Olodaterol (2.5 / 5 μg) Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period. | 40 |
| Tiotropium + Olodaterol (5 / 5 μg) Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period. | 41 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 | 2 |
| Overall Study | Other than stated above | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Olodaterol (5 μg) | Tiotropium + Olodaterol (2.5 / 5 μg) | Tiotropium + Olodaterol (5 / 5 μg) | Total |
|---|---|---|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 7.2 | 70.0 years STANDARD_DEVIATION 7.5 | 68.1 years STANDARD_DEVIATION 7.1 | 69.9 years STANDARD_DEVIATION 7.3 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 40 Participants | 39 Participants | 38 Participants | 117 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 | 21 / 41 | 20 / 40 | 24 / 41 |
| serious Total, serious adverse events | 5 / 41 | 6 / 40 | 3 / 41 |
Outcome results
Primary
Number (%) of Patients With Drug-related AEs
Number (%) of patients with drug-related Adverse Events (AEs).
Time frame: From first drug administration until 21 days after the last administration, upto 392 days
Population: Treated set: This patient set included all patients who received at least 1 dose of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olodaterol (5 μg) | Number (%) of Patients With Drug-related AEs | 4.9 percentage of participants |
| Tiotropium + Olodaterol (2.5 / 5 μg) | Number (%) of Patients With Drug-related AEs | 5.0 percentage of participants |
| Tiotropium + Olodaterol (5 / 5 μg) | Number (%) of Patients With Drug-related AEs | 7.3 percentage of participants |
Secondary
FEV1 AUC0-3h Response
Forced Expiratory Volume in 1 second Area Under Curve (AUC0-3h) response. FEV1 AUC0-3h was calculated using the trapezoidal rule, divided by the duration (3 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. Note: The Mean presented is the unadjusted mean.
Time frame: Baseline and 1 h, 10 min pre-dose and 30 min, 1 h, 2 h, 3 h post-dose after 52 weeks
Population: Full analysis set (FAS): This patient set included all randomised patients who received at least 1 dose of treatment and had both non-missing baseline and at least 1 non-missing post-baseline efficacy measurement. Assignment to FAS was done after implementation of any data handling rules which set measurements to missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olodaterol (5 μg) | FEV1 AUC0-3h Response | 0.132 L | Standard Error 0.03 |
| Tiotropium + Olodaterol (2.5 / 5 μg) | FEV1 AUC0-3h Response | 0.260 L | Standard Error 0.031 |
| Tiotropium + Olodaterol (5 / 5 μg) | FEV1 AUC0-3h Response | 0.237 L | Standard Error 0.024 |
Secondary
Trough FEV1 Response
Trough Forced Expiratory Volume in 1 second Response. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements after 52 weeks. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. Note: The Mean presented is the unadjusted mean.
Time frame: Baseline and 1 h, 10 min pre-dose after 52 weeks
Population: Full analysis set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olodaterol (5 μg) | Trough FEV1 Response | 0.075 L | Standard Error 0.027 |
| Tiotropium + Olodaterol (2.5 / 5 μg) | Trough FEV1 Response | 0.168 L | Standard Error 0.031 |
| Tiotropium + Olodaterol (5 / 5 μg) | Trough FEV1 Response | 0.143 L | Standard Error 0.025 |