Asthma
Conditions
Keywords
Abediterol, Dry powder inhaler, Pressured metered-dose inhaler, Pharmacokinetic, Pharmacodynamic, Safety
Brief summary
The purpose of this study is to investigate the pharmacodynamics of single doses of abediterol given by 2 different devices in participants with asthma. Abediterol (AZD0548) is a potential for once daily treatment of asthma and chronic obstructive pulmonary disease (COPD) in fixed dose combination (FDC) with an inhaled corticosteroid (ICS) or a novel anti-inflammatory agent. The aim of the clinical studies is to enable further investigations in participants with asthma and COPD to evaluate and develop abediterol as an effective long acting bronchodilator with an acceptable safety profile compared to other inhaled bronchodilators on the market, for the treatment of asthma and COPD.
Detailed description
This is a randomised, double-blinded, double-dummy, placebo-controlled, multi-centre, six-way William's design, crossover study to assess the pharmacodynamics, pharmacokinetics, and safety of abediterol single dose, given by dry powder inhaler or pressurised metered-dose inhaler, in patients with asthma, on inhaled corticosteroids. During the screening period, all patients will take their own baseline inhaled corticosteroid for 2 weeks. Patients on long-acting β2-agonist/ inhaled corticosteroids will be switched over to the respective inhaled corticosteroid monocomponent. Patients will be provided salbutamol as rescue medication for use throughout the study. Abediterol is an investigational product in early stages of clinical development, therefore individual participants in the clinical studies may not have a clinical benefit, especially in view of alternative therapies (bronchodilators) being available for the treatment of asthma and COPD.
Interventions
DRUGAbediterol 0.156 μg
Dry powder for inhalation
DRUGAbediterol 2.5 μg
Dry powder for inhalation
DRUGAbediterol 0.05 μg
Pressurised metered-dose inhaler
OTHERPlacebo
Pressurised metered-dose inhaler and dry powder for inhalation.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of informed consent before any study specific procedures. 2. Men or non-pregnant, non-lactating women 18 to 75 years of age, inclusive. 3. Non-smoker or ex-smoker (quit ≥6months prior to Visit 1) with a total smoking history of ≤10 pack years. 4. Documented clinical diagnosis of asthma for ≥6 months before Visit 1 according to GINA guidelines. 5. On stable dose of ICS or ICS/LABA FDC, for at least 1 month prior to Visit 1, at the doses approved in the country of enrolment. 6. Prebronchodilator FEV1 at Visit 2 ≥40% and ≤85% of predicted (1 repetition of the test is allowed before screen failure). 7. Reversibility to salbutamol (per American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria, 2005 ie, ≥12% and ≥200 mL) at Visit 2 (1 repetition of the test is allowed before screen failure). 8. Demonstrate the ability to use the study inhalation device properly. 9. Able to perform repeated pulmonary function testing for FEV1. 10. Able to read, speak and understand German. 11. Patient must agree to all restrictions during the study.
Exclusion criteria
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 2. Participation in another clinical study with an IP during the last 3 months. 3. Known or suspected hypersensitivity to the IP or excipients, including lactose (Note: lactose intolerance is not an exclusion). 4. Systemic steroid use in the 6 weeks before Visit 1. 5. Hospitalization due to asthma in the 6 months prior to Visit 1. 6. Any active pulmonary disease other than asthma. 7. Non-compliance with study procedures in the run in period - as judged by the Investigator. 8. Treatment with biologicals such as monoclonal antibodies or chimeric biomolecules including omalizumab within 6 months or 5 half-lives before Visit 1 (whichever is longer). 9. Treatment with any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to Visit 1. 10. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to Visit 1. 11. Any laboratory abnormality or suspicion of any clinically relevant disease or disorder (on history or examination), including uncontrolled hypertension or uncontrolled diabetes, which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study, or any other safety concerns in the opinion of the Investigator. 12. Known chronic hepatitis or HIV infections at the time of enrolment. 13. Any active malignancy or treatment thereof within the 3 years prior to enrolment. 14. Any clinically important abnormalities in rhythm, conduction, or morphology of the screening 12-lead ECG as judged by the Investigator on the screening ECG. 15. Prolonged QT interval using Fridericia's correction 450 msec for males and 470 msec for females on the screening ECG or family history of long QT syndrome. 16. PR (PQ) interval prolongation (\> 240 msec), intermittent second or third degree atrialventricular (AV) block or AV dissociation on the screening ECG. 17. Implantable cardiac defibrillator and patients with sustained symptomatic ventricular and/or atrial tachyarrhythmia. 18. Any contraindication against the use of sympathomimetic drugs as judged by the Investigator. 19. Unstable angina pectoris or stable angina pectoris classified higher than Canadian Cardiovascular Society Class II, or a myocardial infarction, or stroke within 6 months before Visit 1. 20. History of hospitalisation within 12 months caused by heart failure or a diagnosis of heart failure higher than New York Heart Association Class II. 21. Suspected poor capability to follow instructions of the study, as judged by the Investigator. 22. History of or current alcohol or drug abuse (including marijuana), as judged by the Investigator. 23. Planned in-patient surgery, major dental procedure or hospitalisation during the study. 24. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff, contract research organisation staff and/or staff at the study site). 25. Vulnerable persons (eg, persons kept in detention). 26 Daily rescue medication (salbutamol) use of ≥ 12 puffs for ≥ 3 consecutive days during the run-in period. 27\. Patient who intends to use any concomitant medication not permitted by this protocol or not to meet the restrictions. 28\. Patient on treatment with strong CYP3A4 inhibitors such as ketoconazole or itraconazole or CYP3A4 inducers such as rifampin at Visit 1. 29\. Procedures for withdrawal of incorrectly enrolled patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1). | 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1 | Baseline for FEV1 was defined as the mean of the two measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min), prior to the morning investigational product (IP) administration on Day 1 of each treatment period. If both were missing the screening value was used instead. Trough is defined as the mean of the FEV1 values obtained at 23 h and 24 h after the morning IP administration. If one of the values was missing, the other one was used as trough. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1. | Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1 | The percentage of patients achieving at least 200 mL and 12% increase from baseline in peak FEV1 on Day 1 of each treatment. The peak was the highest value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1. |
| Time to Peak FEV1 at Day 1 | 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1 | The peak is the highest forced expiratory volume in one second (FEV1) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1. |
| Observed Maximum Concentration of Abediterol (Cmax) | Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1. | Observed maximum concentration (Cmax) of Abediterol, taken directly from the individual concentration-time curve. |
| Time (h) to Maximum Concentration of Abediterol (Tmax). | Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1. | Time to maximum concentration (Tmax) of Abediterol (h), taken directly from the individual concentration-time curve. |
| Terminal Rate Constant of Abediterol (λz) | Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1. | Terminal rate constant (λz) of Abediterol, estimated by log-linear least square regression of the terminal part of the concentration-time curve. |
| Terminal Half-life (h) of Abediterol (t½λz) | Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1. | Terminal half-life (h), estimated as (ln2)/λz (t1/2λz). |
| AUClast of Abediterol | Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1. | Area under the plasma concentration-curve of Abediterol from time zero to the time of last quantifiable analyte concentration. |
| AUC of Abediterol. | Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1. | Area under the Abediterol concentration-time curve from time zero extrapolated to infinity (AUC). AUC is estimated by AUClast + Clast/λz where Clast is the last observed quantifiable concentration (AUC). PK blood samples were collected 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1 (Note that 24 h and 36 h time-points post-dose correspond to Day 2). |
| Apparent Plasma Clearance for Abediterol (CL/F). | Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1. | Apparent plasma clearance for parent drug estimated as dose divided by AUC (CL/F). |
| Apparent Volume of Distribution for Abediterol at Terminal Phase (Vz/F). | Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1. | Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz (Vz/F). |
| Number of Participants With Any Treatment-emergent Adverse Event | From screening (Day -14) up to follow-up phone call (14 days after last IP administration). | All treatment emergent adverse events (TEAEs), including serious AEs. An AE is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An AE was considered a TEAE if it was not present prior to the date of the first dose of IP or was present prior to the date of the first dose of IP, but increased in severity after IP administration. |
| Mean Residence Time (MRT) of Abediterol. | Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1. | Mean residence time (h), calculated by AUMC/AUC, where AUMC is the area under the first moment-time curve (MRT). |
| Time to Peak FVC at Day 1 | 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1 | The peak is the highest forced vital capacity (FVC) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1. |
| Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1. | Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1 | The percentage of patients achieving at least 200 mL and 12% increase from baseline in trough forced expiratory volume in one second (FEV1). Trough was defined as the mean of the FEV1 values obtained at 23 hours and 24 hours after the morning IP administration. |
| Change From Baseline in Peak FEV1. | Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1 | The peak is the highest forced expiratory volume in one second (FEV1) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1. |
| Change From Baseline in Normalised FEV1 AUC0-24. | 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1 | Change from baseline in normalised FEV1 area under the concentration-curve of Abediterol from time zero to 24 hours post-dose. Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead. |
| Change From Baseline in Normalised FEV1 AUC0-12. | 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, and 12 h post-dose on Day 1 | Change from baseline in normalised FEV1 area under the concentration time curve for Abediterol from time zero to 12 hours post-dose. Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead. |
| Change From Baseline in Normalised FEV1 AUC0-6. | 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, and 6 h post dose on Day 1 | Change from baseline in normalised FEV1 area under the concentration-curve for Abediterol from time zero to 6 hours post-dose. Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead. |
| Change From Baseline in Normalised FEV1 AUC12-24. | 45 mins and 15 mins predose, and 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1 | Change from baseline in normalised FEV1 area under the concentration-curve for Abediterol from time 12 hours post-dose to 24 hours post-dose. Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead. |
| Change From Baseline in Peak FVC. | Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1 | Baseline for FVC was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead. The peak is the highest forced vital capacity (FVC) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1. |
| Change From Baseline in Trough FVC. | 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1 | Baseline for FVC was defined as the mean of the two measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min), prior to the morning investigational product (IP)administration on Day 1 of each treatment period. If both were missing the screening value was used instead. Trough was defined as the mean of the FEV1 values obtained at 23 h and 24 h after the morning IP administration. If one of the values was missing, the other one was used as trough. |
| Change From Baseline in Normalised FVC AUC0-24. | 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1 | Change from baseline in normalised FVC area under the concentration curve for Abediterol from time zero to 24 hours post-dose. Baseline for FVC was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FVC from Visit 2) was used instead. |
| Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | Up to last treatment visit (Day 112) | Standard 12-lead ECG evaluations were performed prior to IP administration and 1, 4 and 24 h post IP administration at randomisation and after each IP administration. ECGs were recorded after approximately 5 minutes resting in supine position before any blood sampling and spirometry test, preferably always by the same technician for each patient. Clinically significant abnormalities were defined as listed in the table below for QT interval, QTcB, QTcF, QRS interval, PR interval and heart rate (HR). BL incr. = increase from baseline. |
Countries
Germany
Participant flow
Recruitment details
This study was conducted at four sites in Germany. The first patient was screened 21 June 2016, the last patient visit was 29 November 2016.
Pre-assignment details
In total, 42 patients were screened; 30 patients were eligible to participate and were randomised.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Population | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Washout Between Periods 3 and 4 | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Study Population |
|---|---|
| Age, Continuous | 54.2 Years STANDARD_DEVIATION 10 |
| Sex/Gender, Customized Female | 10 Participants |
| Sex/Gender, Customized Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 29 |
| other Total, other adverse events | 3 / 29 | 2 / 29 | 4 / 30 | 5 / 30 | 3 / 30 | 8 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 29 |
Outcome results
Primary
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1).
Baseline for FEV1 was defined as the mean of the two measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min), prior to the morning investigational product (IP) administration on Day 1 of each treatment period. If both were missing the screening value was used instead. Trough is defined as the mean of the FEV1 values obtained at 23 h and 24 h after the morning IP administration. If one of the values was missing, the other one was used as trough.
Time frame: 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1). | 0.225 Liters | Standard Deviation 0.192 |
| Abediterol Dry Powder Inhaler 2.5 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1). | 0.400 Liters | Standard Deviation 0.269 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1). | 0.108 Liters | Standard Deviation 0.212 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1). | 0.170 Liters | Standard Deviation 0.207 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1). | 0.407 Liters | Standard Deviation 0.24 |
| Placebo | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1). | -0.001 Liters | Standard Deviation 0.244 |
p-value: <0.000195% CI: [0.1324, 0.3118]ANCOVA
p-value: <0.000195% CI: [0.3146, 0.4938]ANCOVA
p-value: 0.020795% CI: [0.0164, 0.1949]ANCOVA
p-value: 0.000295% CI: [0.081, 0.2592]ANCOVA
p-value: <0.000195% CI: [0.317, 0.4955]ANCOVA
Secondary
Apparent Plasma Clearance for Abediterol (CL/F).
Apparent plasma clearance for parent drug estimated as dose divided by AUC (CL/F).
Time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Population: The PK analysis set, defined as all randomised subjects who took at least one dose of IP and had at least one evaluable relevant PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 2.5 μg | Apparent Plasma Clearance for Abediterol (CL/F). | 196.4 L/h | Geometric Coefficient of Variation 43.26 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Apparent Plasma Clearance for Abediterol (CL/F). | 225.6 L/h | Geometric Coefficient of Variation 50.01 |
Secondary
Apparent Volume of Distribution for Abediterol at Terminal Phase (Vz/F).
Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz (Vz/F).
Time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Population: The PK analysis set, defined as all randomised subjects who took at least one dose of IP and had at least one evaluable relevant PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 2.5 μg | Apparent Volume of Distribution for Abediterol at Terminal Phase (Vz/F). | 4008 Liters | Geometric Coefficient of Variation 37.41 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Apparent Volume of Distribution for Abediterol at Terminal Phase (Vz/F). | 3690 Liters | Geometric Coefficient of Variation 49.93 |
Secondary
AUClast of Abediterol
Area under the plasma concentration-curve of Abediterol from time zero to the time of last quantifiable analyte concentration.
Time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Population: The PK analysis set, defined as all randomised subjects who took at least one dose of IP and had at least one evaluable relevant PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 2.5 μg | AUClast of Abediterol | 9.092 pg.h/mL | Geometric Coefficient of Variation 53.95 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | AUClast of Abediterol | 7.674 pg.h/mL | Geometric Coefficient of Variation 132.5 |
Secondary
AUC of Abediterol.
Area under the Abediterol concentration-time curve from time zero extrapolated to infinity (AUC). AUC is estimated by AUClast + Clast/λz where Clast is the last observed quantifiable concentration (AUC). PK blood samples were collected 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1 (Note that 24 h and 36 h time-points post-dose correspond to Day 2).
Time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Population: The PK analysis set, defined as all randomised subjects who took at least one dose of IP and had at least one evaluable relevant PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 2.5 μg | AUC of Abediterol. | 12.73 pg.h/mL | Geometric Coefficient of Variation 43.26 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | AUC of Abediterol. | 11.08 pg.h/mL | Geometric Coefficient of Variation 50.01 |
Secondary
Change From Baseline in Normalised FEV1 AUC0-12.
Change from baseline in normalised FEV1 area under the concentration time curve for Abediterol from time zero to 12 hours post-dose. Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead.
Time frame: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, and 12 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Change From Baseline in Normalised FEV1 AUC0-12. | 0.3194 Liters | Standard Error 0.0504 |
| Abediterol Dry Powder Inhaler 2.5 μg | Change From Baseline in Normalised FEV1 AUC0-12. | 0.5135 Liters | Standard Error 0.0504 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Change From Baseline in Normalised FEV1 AUC0-12. | 0.1575 Liters | Standard Error 0.05 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Change From Baseline in Normalised FEV1 AUC0-12. | 0.2770 Liters | Standard Error 0.05 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Change From Baseline in Normalised FEV1 AUC0-12. | 0.5104 Liters | Standard Error 0.05 |
| Placebo | Change From Baseline in Normalised FEV1 AUC0-12. | 0.0629 Liters | Standard Error 0.0507 |
Secondary
Change From Baseline in Normalised FEV1 AUC0-24.
Change from baseline in normalised FEV1 area under the concentration-curve of Abediterol from time zero to 24 hours post-dose. Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead.
Time frame: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Change From Baseline in Normalised FEV1 AUC0-24. | 0.2767 Liters | Standard Error 0.0468 |
| Abediterol Dry Powder Inhaler 2.5 μg | Change From Baseline in Normalised FEV1 AUC0-24. | 0.4813 Liters | Standard Error 0.0468 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Change From Baseline in Normalised FEV1 AUC0-24. | 0.0933 Liters | Standard Error 0.0465 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Change From Baseline in Normalised FEV1 AUC0-24. | 0.2091 Liters | Standard Error 0.0464 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Change From Baseline in Normalised FEV1 AUC0-24. | 0.4635 Liters | Standard Error 0.0464 |
| Placebo | Change From Baseline in Normalised FEV1 AUC0-24. | 0.0124 Liters | Standard Error 0.0472 |
Secondary
Change From Baseline in Normalised FEV1 AUC0-6.
Change from baseline in normalised FEV1 area under the concentration-curve for Abediterol from time zero to 6 hours post-dose. Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead.
Time frame: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, and 6 h post dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Change From Baseline in Normalised FEV1 AUC0-6. | 0.3198 Liters | Standard Error 0.0485 |
| Abediterol Dry Powder Inhaler 2.5 μg | Change From Baseline in Normalised FEV1 AUC0-6. | 0.5044 Liters | Standard Error 0.0485 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Change From Baseline in Normalised FEV1 AUC0-6. | 0.1646 Liters | Standard Error 0.0481 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Change From Baseline in Normalised FEV1 AUC0-6. | 0.2987 Liters | Standard Error 0.048 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Change From Baseline in Normalised FEV1 AUC0-6. | 0.5127 Liters | Standard Error 0.0481 |
| Placebo | Change From Baseline in Normalised FEV1 AUC0-6. | 0.0654 Liters | Standard Error 0.0484 |
Secondary
Change From Baseline in Normalised FEV1 AUC12-24.
Change from baseline in normalised FEV1 area under the concentration-curve for Abediterol from time 12 hours post-dose to 24 hours post-dose. Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead.
Time frame: 45 mins and 15 mins predose, and 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Change From Baseline in Normalised FEV1 AUC12-24. | 0.2339 Liters | Standard Error 0.0479 |
| Abediterol Dry Powder Inhaler 2.5 μg | Change From Baseline in Normalised FEV1 AUC12-24. | 0.4479 Liters | Standard Error 0.0479 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Change From Baseline in Normalised FEV1 AUC12-24. | 0.0504 Liters | Standard Error 0.0479 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Change From Baseline in Normalised FEV1 AUC12-24. | 0.1421 Liters | Standard Error 0.0474 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Change From Baseline in Normalised FEV1 AUC12-24. | 0.4169 Liters | Standard Error 0.0474 |
| Placebo | Change From Baseline in Normalised FEV1 AUC12-24. | -0.0346 Liters | Standard Error 0.0487 |
Secondary
Change From Baseline in Normalised FVC AUC0-24.
Change from baseline in normalised FVC area under the concentration curve for Abediterol from time zero to 24 hours post-dose. Baseline for FVC was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FVC from Visit 2) was used instead.
Time frame: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Change From Baseline in Normalised FVC AUC0-24. | 0.2057 Liters | Standard Error 0.0513 |
| Abediterol Dry Powder Inhaler 2.5 μg | Change From Baseline in Normalised FVC AUC0-24. | 0.3646 Liters | Standard Error 0.0512 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Change From Baseline in Normalised FVC AUC0-24. | 0.0704 Liters | Standard Error 0.051 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Change From Baseline in Normalised FVC AUC0-24. | 0.1445 Liters | Standard Error 0.0508 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Change From Baseline in Normalised FVC AUC0-24. | 0.3409 Liters | Standard Error 0.0509 |
| Placebo | Change From Baseline in Normalised FVC AUC0-24. | 0.0309 Liters | Standard Error 0.0517 |
Secondary
Change From Baseline in Peak FEV1.
The peak is the highest forced expiratory volume in one second (FEV1) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Time frame: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Change From Baseline in Peak FEV1. | 0.4232 Liters | Standard Error 0.0487 |
| Abediterol Dry Powder Inhaler 2.5 μg | Change From Baseline in Peak FEV1. | 0.6018 Liters | Standard Error 0.0487 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Change From Baseline in Peak FEV1. | 0.2930 Liters | Standard Error 0.0483 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Change From Baseline in Peak FEV1. | 0.4280 Liters | Standard Error 0.0482 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Change From Baseline in Peak FEV1. | 0.6266 Liters | Standard Error 0.0483 |
| Placebo | Change From Baseline in Peak FEV1. | 0.1880 Liters | Standard Error 0.0486 |
Secondary
Change From Baseline in Peak FVC.
Baseline for FVC was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead. The peak is the highest forced vital capacity (FVC) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Time frame: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Change From Baseline in Peak FVC. | 0.3478 Liters | Standard Error 0.0553 |
| Abediterol Dry Powder Inhaler 2.5 μg | Change From Baseline in Peak FVC. | 0.4932 Liters | Standard Error 0.0552 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Change From Baseline in Peak FVC. | 0.2867 Liters | Standard Error 0.055 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Change From Baseline in Peak FVC. | 0.3756 Liters | Standard Error 0.0548 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Change From Baseline in Peak FVC. | 0.5059 Liters | Standard Error 0.0549 |
| Placebo | Change From Baseline in Peak FVC. | 0.2347 Liters | Standard Error 0.0552 |
Secondary
Change From Baseline in Trough FVC.
Baseline for FVC was defined as the mean of the two measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min), prior to the morning investigational product (IP)administration on Day 1 of each treatment period. If both were missing the screening value was used instead. Trough was defined as the mean of the FEV1 values obtained at 23 h and 24 h after the morning IP administration. If one of the values was missing, the other one was used as trough.
Time frame: 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Change From Baseline in Trough FVC. | 0.1702 Liters | Standard Error 0.0523 |
| Abediterol Dry Powder Inhaler 2.5 μg | Change From Baseline in Trough FVC. | 0.3023 Liters | Standard Error 0.0523 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Change From Baseline in Trough FVC. | 0.0931 Liters | Standard Error 0.0519 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Change From Baseline in Trough FVC. | 0.1218 Liters | Standard Error 0.0517 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Change From Baseline in Trough FVC. | 0.3134 Liters | Standard Error 0.0518 |
| Placebo | Change From Baseline in Trough FVC. | 0.0077 Liters | Standard Error 0.0523 |
Secondary
Mean Residence Time (MRT) of Abediterol.
Mean residence time (h), calculated by AUMC/AUC, where AUMC is the area under the first moment-time curve (MRT).
Time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Population: The PK analysis set, defined as all randomised subjects who took at least one dose of IP and had at least one evaluable relevant PK parameter
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 2.5 μg | Mean Residence Time (MRT) of Abediterol. | 19.73 Hours | Geometric Coefficient of Variation 35.48 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Mean Residence Time (MRT) of Abediterol. | 15.59 Hours | Geometric Coefficient of Variation 29.57 |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event
All treatment emergent adverse events (TEAEs), including serious AEs. An AE is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An AE was considered a TEAE if it was not present prior to the date of the first dose of IP or was present prior to the date of the first dose of IP, but increased in severity after IP administration.
Time frame: From screening (Day -14) up to follow-up phone call (14 days after last IP administration).
Population: All randomised participants who received at least one dose of investigational product
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Any Treatment-emergent Adverse Event | 7 Number of participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Any Treatment-emergent Adverse Event | 10 Number of participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Any Treatment-emergent Adverse Event | 7 Number of participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Any Treatment-emergent Adverse Event | 6 Number of participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Any Treatment-emergent Adverse Event | 7 Number of participants |
| Placebo | Number of Participants With Any Treatment-emergent Adverse Event | 12 Number of participants |
Secondary
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
Standard 12-lead ECG evaluations were performed prior to IP administration and 1, 4 and 24 h post IP administration at randomisation and after each IP administration. ECGs were recorded after approximately 5 minutes resting in supine position before any blood sampling and spirometry test, preferably always by the same technician for each patient. Clinically significant abnormalities were defined as listed in the table below for QT interval, QTcB, QTcF, QRS interval, PR interval and heart rate (HR). BL incr. = increase from baseline.
Time frame: Up to last treatment visit (Day 112)
Population: All randomised participants who received at least one dose of investigational product
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 1,1h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,1h) | 2 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,1h) | 1 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,4h) | 1 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,1h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,1h) | 1 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QRS duration >=100 and incr. >=25%(Day 1,4h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >60msec(Day 1,4h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,1h) | 2 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,4h) | 3 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,4h) | 0 Participants |
| Abediterol Dry Powder Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 2,24h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,1h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,4h) | 3 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 2,24h) | 2 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,4h) | 2 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 2,24h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,1h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 1,1h) | 0 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QRS duration >=100 and incr. >=25%(Day 1,4h) | 0 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 2,24h) | 0 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 2,24h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,1h) | 2 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval BL incr. >30-<=60msec(Day 1,4h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,4h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,1h) | 3 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,1h) | 1 Participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >60msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 2,24h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,4h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,1h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 2,24h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 2,24h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,1h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,1h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 1,1h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >60msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,4h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,1h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,1h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QRS duration >=100 and incr. >=25%(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 2,24h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,1h) | 4 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,1h) | 4 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,4h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,1h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >60msec(Day 1,4h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 2,24h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,1h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,4h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 2,24h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,1h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 2,24h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QRS duration >=100 and incr. >=25%(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 1,1h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,1h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 2,24h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 1,1h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >60msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,4h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QRS duration >=100 and incr. >=25%(Day 1,4h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,4h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,1h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 2,24h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,1h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 2,24h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 1,4h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,1h) | 0 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,1h) | 1 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,4h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 2,24h) | 2 Participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 2,24h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 2,24h) | 2 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >60msec(Day 1,4h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 2,24h) | 1 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,4h) | 1 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,4h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,1h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 1,1h) | 4 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 2,24h) | 1 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | HR <=50 bpm and decr. >=15%(Day 1,1h) | 2 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 2,24h) | 1 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval >450-<=480msec(Day 2,24h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcF interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,1h) | 3 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QRS duration >=100 and incr. >=25%(Day 1,4h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,4h) | 1 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval >450-<=480msec(Day 1,1h) | 1 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | PR interval >=200 and incr. >=25%(Day 1,1h) | 1 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 2,24h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QTcB interval BL incr. >30-<=60msec(Day 1,4h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval >450-<=480msec(Day 1,4h) | 0 Participants |
| Placebo | Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters | QT interval BL incr. >30-<=60msec(Day 2,24h) | 0 Participants |
Secondary
Observed Maximum Concentration of Abediterol (Cmax)
Observed maximum concentration (Cmax) of Abediterol, taken directly from the individual concentration-time curve.
Time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Population: The PK analysis set, defined as all randomised subjects who took at least one dose of IP and had at least one evaluable relevant PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Observed Maximum Concentration of Abediterol (Cmax) | 0.2299 pg/mL | Geometric Coefficient of Variation 117.3 |
| Abediterol Dry Powder Inhaler 2.5 μg | Observed Maximum Concentration of Abediterol (Cmax) | 1.092 pg/mL | Geometric Coefficient of Variation 47.34 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Observed Maximum Concentration of Abediterol (Cmax) | 0.2460 pg/mL | Geometric Coefficient of Variation 128.7 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Observed Maximum Concentration of Abediterol (Cmax) | 1.211 pg/mL | Geometric Coefficient of Variation 82.21 |
Secondary
Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1.
The percentage of patients achieving at least 200 mL and 12% increase from baseline in peak FEV1 on Day 1 of each treatment. The peak was the highest value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Time frame: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1. | 72.41 Percentage of participants |
| Abediterol Dry Powder Inhaler 2.5 μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1. | 82.76 Percentage of participants |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1. | 56.67 Percentage of participants |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1. | 73.33 Percentage of participants |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1. | 90.00 Percentage of participants |
| Placebo | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1. | 24.14 Percentage of participants |
Secondary
Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1.
The percentage of patients achieving at least 200 mL and 12% increase from baseline in trough forced expiratory volume in one second (FEV1). Trough was defined as the mean of the FEV1 values obtained at 23 hours and 24 hours after the morning IP administration.
Time frame: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1. | 31.03 Percentage of patients |
| Abediterol Dry Powder Inhaler 2.5 μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1. | 72.41 Percentage of patients |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1. | 23.33 Percentage of patients |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1. | 26.67 Percentage of patients |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1. | 76.67 Percentage of patients |
| Placebo | Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1. | 10.34 Percentage of patients |
Secondary
Terminal Half-life (h) of Abediterol (t½λz)
Terminal half-life (h), estimated as (ln2)/λz (t1/2λz).
Time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Population: The PK analysis set, defined as all randomised subjects who took at least one dose of IP and had at least one evaluable relevant PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 2.5 μg | Terminal Half-life (h) of Abediterol (t½λz) | 14.99 Hours | Standard Deviation 4.827 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Terminal Half-life (h) of Abediterol (t½λz) | 11.85 Hours | Standard Deviation 3.533 |
Secondary
Terminal Rate Constant of Abediterol (λz)
Terminal rate constant (λz) of Abediterol, estimated by log-linear least square regression of the terminal part of the concentration-time curve.
Time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Population: The PK analysis set, defined as all randomised subjects who took at least one dose of IP and had at least one evaluable relevant PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 2.5 μg | Terminal Rate Constant of Abediterol (λz) | 0.0526 l/hour | Standard Deviation 0.0228 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Terminal Rate Constant of Abediterol (λz) | 0.0640 l/hour | Standard Deviation 0.0201 |
Secondary
Time (h) to Maximum Concentration of Abediterol (Tmax).
Time to maximum concentration (Tmax) of Abediterol (h), taken directly from the individual concentration-time curve.
Time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Population: The PK analysis set, defined as all randomised subjects who took at least one dose of IP and had at least one evaluable relevant PK parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Time (h) to Maximum Concentration of Abediterol (Tmax). | 0.980 Hours |
| Abediterol Dry Powder Inhaler 2.5 μg | Time (h) to Maximum Concentration of Abediterol (Tmax). | 0.500 Hours |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Time (h) to Maximum Concentration of Abediterol (Tmax). | 0.735 Hours |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Time (h) to Maximum Concentration of Abediterol (Tmax). | 0.620 Hours |
Secondary
Time to Peak FEV1 at Day 1
The peak is the highest forced expiratory volume in one second (FEV1) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Time frame: 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Time to Peak FEV1 at Day 1 | 3.7 Hours | Standard Deviation 1.8 |
| Abediterol Dry Powder Inhaler 2.5 μg | Time to Peak FEV1 at Day 1 | 3.3 Hours | Standard Deviation 1.8 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Time to Peak FEV1 at Day 1 | 3.0 Hours | Standard Deviation 1.9 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Time to Peak FEV1 at Day 1 | 3.5 Hours | Standard Deviation 1.7 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Time to Peak FEV1 at Day 1 | 3.6 Hours | Standard Deviation 2 |
| Placebo | Time to Peak FEV1 at Day 1 | 2.9 Hours | Standard Deviation 2.2 |
Secondary
Time to Peak FVC at Day 1
The peak is the highest forced vital capacity (FVC) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Time frame: 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abediterol Dry Powder Inhaler 0.156 μg | Time to Peak FVC at Day 1 | 2.8 Hours | Standard Deviation 1.8 |
| Abediterol Dry Powder Inhaler 2.5 μg | Time to Peak FVC at Day 1 | 2.3 Hours | Standard Deviation 1.9 |
| Abediterol Pressurised Metered-dose Inhaler 0.05μg | Time to Peak FVC at Day 1 | 2.8 Hours | Standard Deviation 2.2 |
| Abediterol Pressurised Metered-dose Inhaler 0.156 μg | Time to Peak FVC at Day 1 | 3.2 Hours | Standard Deviation 2.3 |
| Abediterol Pressurised Metered-dose Inhaler 2.5μg | Time to Peak FVC at Day 1 | 3.4 Hours | Standard Deviation 2.2 |
| Placebo | Time to Peak FVC at Day 1 | 1.9 Hours | Standard Deviation 1.8 |