Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The primary objective of this study is to assess pharmacokinetics of tiotropium + olodaterol fixed-dose combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) delivered by the RESPIMAT inhaler after 3 weeks once daily treatment in Japanese patients with COPD.
Interventions
DRUGTiotropium (high dose) + Olodaterol
Tiotropium + Olodaterol solution for inhalation
DRUGTiotropium (low dose) + Olodaterol
Tiotropium + Olodaterol solution for inhalation
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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=\<30% of predicted normal and\< 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. A marked baseline prolongation of QT/QTc interval 7. A history of additional risk factors for Torsade de Pointes (TdP) 8. History of myocardial infarction within 1 year of screening visit 9. Unstable or life-threatening cardiac arrhythmia 10. Hospitalization for heart failure within the past year 11. Known active tuberculosis 12. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years 13. History of life-threatening pulmonary obstruction 14. History of cystic fibrosis 15. Clinically evident bronchiectasis 16. History of significant alcohol or drug abuse 17. Thoracotomy with pulmonary resection 18. Oral ß-adrenergics 19. Oral corticosteroid medication at unstable doses 20. Regular use of daytime oxygen therapy for more than one hour per day 21. Pulmonary rehabilitation program in the six weeks prior to the screening visit 22. Investigational drug within one month or six half lives (whichever is greater) prior to screening visit 23. Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA 24. Pregnant or nursing women 25. Women of childbearing potential not using a highly effective method of birth control 26. Patients who have previously been randomized in this study or are currently participating in another study 27. Patients who are unable to comply with pulmonary medication restrictions 28. Patients with narrow-angle glaucoma or micturition disorder due to prostatic hyperplasia etc 29. Patients being treated with medications that prolong the QT/QTc interval
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CLR,t1-t2,ss (Tiotropium) | from 0 to 4 hours following drug administration on day 21 | Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg). |
| Aet1-t2,ss (Tiotropium) | from 0 to 4 hours following drug administration on day 21 | Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| fe t1-t2,ss (Tiotropium) | from 0 to 4 hours following drug administration on day 21 | Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| Cmax,ss (Olodaterol) | 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21 | Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| AUCt1-t2,ss (Olodaterol) | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21 | Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| AUC0-tz,ss (Olodaterol) | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21 | Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| Tmax,ss (Olodaterol) | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21 | Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| Aet1-t2,ss (Olodaterol) | from 0 to 4 hours following drug administration on day 21 | Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| fe t1-t2,ss (Olodaterol) | from 0 to 4 hours following drug administration on day 21 | Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| CLR,t1-t2,ss (Olodaterol) | from 0 to 4 hours following drug administration on day 21 | Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| Cmax,ss (Tiotropium) | 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21 | Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| AUCt1-t2,ss (Tiotropium) | 15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21 | Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| AUC0-tz,ss (Tiotropium) | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21 | Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
| Tmax,ss (Tiotropium) | 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21 | Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose | Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events. There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG. |
| Number of Participants With Adverse Events (Including Assessment Based on Physical Examination) | up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose | Outcome data show are the number of patients with an adverse event including the assessment based on physical examination. |
Countries
Japan
Participant flow
Pre-assignment details
This is a randomised, open-label, parallel group trial in which 3 weeks of randomised treatment are preceded by 2-week screening period and followed by 3-week follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| Tiotropium + Olodaterol (5µg/5µg) Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks. | 16 |
| Tiotropium + Olodaterol (2.5µg/5µg) Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks. | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | other than stated above | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Tiotropium + Olodaterol (5µg/5µg) | Tiotropium + Olodaterol (2.5µg/5µg) | Total |
|---|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 10.5 | 69.4 years STANDARD_DEVIATION 7.8 | 66.4 years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 16 | 2 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Aet1-t2,ss (Olodaterol)
Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: from 0 to 4 hours following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | Aet1-t2,ss (Olodaterol) | 74.8 nanogram (ng) | Geometric Coefficient of Variation 100 |
| Tiotropium + Olodaterol (2.5µg/5µg) | Aet1-t2,ss (Olodaterol) | 50.0 nanogram (ng) | Geometric Coefficient of Variation 123 |
Primary
Aet1-t2,ss (Tiotropium)
Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: from 0 to 4 hours following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | Aet1-t2,ss (Tiotropium) | 336 nanogram (ng) | Geometric Coefficient of Variation 119 |
| Tiotropium + Olodaterol (2.5µg/5µg) | Aet1-t2,ss (Tiotropium) | 122 nanogram (ng) | Geometric Coefficient of Variation 118 |
Primary
AUC0-tz,ss (Olodaterol)
Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | AUC0-tz,ss (Olodaterol) | 9.94 pg*h/mL | Geometric Coefficient of Variation 29.9 |
| Tiotropium + Olodaterol (2.5µg/5µg) | AUC0-tz,ss (Olodaterol) | 6.85 pg*h/mL | Geometric Coefficient of Variation 105 |
Primary
AUC0-tz,ss (Tiotropium)
Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | AUC0-tz,ss (Tiotropium) | 23.3 pg*h/mL | Geometric Coefficient of Variation 44.8 |
| Tiotropium + Olodaterol (2.5µg/5µg) | AUC0-tz,ss (Tiotropium) | 7.99 pg*h/mL | Geometric Coefficient of Variation 131 |
Primary
AUCt1-t2,ss (Olodaterol)
Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | AUCt1-t2,ss (Olodaterol) | 9.94 pg*h/mL | Geometric Coefficient of Variation 29.9 |
| Tiotropium + Olodaterol (2.5µg/5µg) | AUCt1-t2,ss (Olodaterol) | 8.14 pg*h/mL | Geometric Coefficient of Variation 65.5 |
Primary
AUCt1-t2,ss (Tiotropium)
Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | AUCt1-t2,ss (Tiotropium) | 14.8 pg*h/mL | Geometric Coefficient of Variation 50.7 |
| Tiotropium + Olodaterol (2.5µg/5µg) | AUCt1-t2,ss (Tiotropium) | 7.00 pg*h/mL | Geometric Coefficient of Variation 52.8 |
Primary
CLR,t1-t2,ss (Olodaterol)
Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: from 0 to 4 hours following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | CLR,t1-t2,ss (Olodaterol) | 152 mL/min | Geometric Coefficient of Variation 48.7 |
| Tiotropium + Olodaterol (2.5µg/5µg) | CLR,t1-t2,ss (Olodaterol) | 148 mL/min | Geometric Coefficient of Variation 42.8 |
Primary
CLR,t1-t2,ss (Tiotropium)
Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).
Time frame: from 0 to 4 hours following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | CLR,t1-t2,ss (Tiotropium) | 292 mL/min | Geometric Coefficient of Variation 44.6 |
Primary
Cmax,ss (Olodaterol)
Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21
Population: The Pharmacokinetic (PK) set was defined as all treated patients who have at least 1 PK parameter in the treatment period without PK related important protocol violations. Two patients prematurely stopped the trial medication and had no PK measurement at Visit 3 (day 21) and were excluded from the PK set. Thus, the PK set included 30 patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | Cmax,ss (Olodaterol) | 4.33 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 53.7 |
| Tiotropium + Olodaterol (2.5µg/5µg) | Cmax,ss (Olodaterol) | 2.82 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 106 |
Primary
Cmax,ss (Tiotropium)
Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | Cmax,ss (Tiotropium) | 16.5 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 92 |
| Tiotropium + Olodaterol (2.5µg/5µg) | Cmax,ss (Tiotropium) | 6.49 picogram/milliliter (pg/mL) | Geometric Coefficient of Variation 50.4 |
Primary
fe t1-t2,ss (Olodaterol)
Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: from 0 to 4 hours following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | fe t1-t2,ss (Olodaterol) | 1.50 percentage of dose | Geometric Coefficient of Variation 100 |
| Tiotropium + Olodaterol (2.5µg/5µg) | fe t1-t2,ss (Olodaterol) | 0.999 percentage of dose | Geometric Coefficient of Variation 123 |
Primary
fe t1-t2,ss (Tiotropium)
Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: from 0 to 4 hours following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | fe t1-t2,ss (Tiotropium) | 6.72 percentage of dose | Geometric Coefficient of Variation 119 |
| Tiotropium + Olodaterol (2.5µg/5µg) | fe t1-t2,ss (Tiotropium) | 4.89 percentage of dose | Geometric Coefficient of Variation 118 |
Primary
Tmax,ss (Olodaterol)
Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | Tmax,ss (Olodaterol) | 0.183 h |
| Tiotropium + Olodaterol (2.5µg/5µg) | Tmax,ss (Olodaterol) | 0.217 h |
Primary
Tmax,ss (Tiotropium)
Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21
Population: The Pharmacokinetic (PK) set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | Tmax,ss (Tiotropium) | 0.100 h |
| Tiotropium + Olodaterol (2.5µg/5µg) | Tmax,ss (Tiotropium) | 0.100 h |
Secondary
Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)
Outcome data show are the number of patients with an adverse event including the assessment based on physical examination.
Time frame: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose
Population: Treated Set (TS) includes all randomised patients who received at least one dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | Number of Participants With Adverse Events (Including Assessment Based on Physical Examination) | 4 participants |
| Tiotropium + Olodaterol (2.5µg/5µg) | Number of Participants With Adverse Events (Including Assessment Based on Physical Examination) | 2 participants |
Secondary
Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG
Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events. There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG.
Time frame: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose
Population: The treated Set (TS).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tiotropium + Olodaterol (5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | AEs reported related to ECG | 0 participants |
| Tiotropium + Olodaterol (5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | Blood creatine phosphokinase increased | 1 participants |
| Tiotropium + Olodaterol (5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | Haematuria | 0 participants |
| Tiotropium + Olodaterol (5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | Blood urine present | 1 participants |
| Tiotropium + Olodaterol (5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | AEs reported related to vital signs | 0 participants |
| Tiotropium + Olodaterol (2.5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | Blood urine present | 0 participants |
| Tiotropium + Olodaterol (2.5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | AEs reported related to vital signs | 0 participants |
| Tiotropium + Olodaterol (2.5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | AEs reported related to ECG | 0 participants |
| Tiotropium + Olodaterol (2.5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | Haematuria | 1 participants |
| Tiotropium + Olodaterol (2.5µg/5µg) | Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG | Blood creatine phosphokinase increased | 0 participants |