Trial Outcomes & Findings for A Single Dose PD & PK Study With Two Formulations of Abediterol in Patients With Asthma (NCT NCT02777827)
NCT ID: NCT02777827
Last Updated: 2019-01-24
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1
Results posted on
2019-01-24
Participant Flow
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.
In total, 42 patients were screened; 30 patients were eligible to participate and were randomised.
Participant milestones
| Measure |
Sequence 1
Abediterol dry powder inhaler (DPI) 0.156 μg, followed by Abediterol pressurised metered-dose inhaler (pMDI) 0.05 μg; Placebo; Abediterol pMDI 0.156 μg; Abediterol DPI 2.5 μg; Abediterol pMDI 2.5 μg
|
Sequence 2
Abediterol pressurised metered-dose inhaler (pMDI) 0.05 μg, followed by Abediterol pMDI 0.156 μg; Abediterol dry powder inhaler (DPI) 0.156 μg; Abediterol pMDI 2.5 μg; Placebo; Abediterol DPI 2.5 μg
|
Sequence 3
Abediterol pressurised metered-dose inhaler (pMDI) 0.156 μg, followed by Abediterol pMDI 2.5 μg; Abediterol pMDI 0.05 μg; Abediterol dry powder inhaler (DPI) 2.5 μg; Abediterol DPI 0.156 μg; Placebo
|
Sequence 4
Abediterol dry powder inhaler (DPI) 2.5 μg, followed by Placebo; Abediterol pressurised metered-dose inhaler (pMDI) 2.5 μg; Abediterol DPI 0.156 μg; Abediterol pMDI 0.156 μg; Abediterol pMDI 0.05 μg
|
Sequence 5
Abediterol pressurised metered-dose inhaler (pMDI) 2.5 μg, followed by Abediterol dry powder inhaler (DPI) 2.5 μg; Abediterol pMDI 0.156 μg; Placebo; Abediterol pMDI 0.05 μg; Abediterol DPI 0.156 μg
|
Sequence 6
Placebo, followed by Abediterol dry powder inhaler (DPI) 0.156 μg; Abediterol DPI 2.5 μg; Abediterol pressurised metered-dose inhaler (pMDI) 0.05 μg; Abediterol pMDI 2.5 μg; Abediterol pMDI 0.156 μg
|
|---|---|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Treatment Period 1
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Between Periods 1 and 2
STARTED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Washout Between Periods 1 and 2
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Washout Between Periods 1 and 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2
STARTED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Treatment Period 2
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Between Periods 2 and 3
STARTED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Washout Between Periods 2 and 3
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Washout Between Periods 2 and 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3
STARTED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Treatment Period 3
COMPLETED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Treatment Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Between Periods 3 and 4
STARTED
|
5
|
5
|
5
|
5
|
4
|
6
|
|
Washout Between Periods 3 and 4
COMPLETED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Washout Between Periods 3 and 4
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Treatment Period 4
STARTED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Treatment Period 4
COMPLETED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Treatment Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Between Periods 4 and 5
STARTED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Washout Between Periods 4 and 5
COMPLETED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Washout Between Periods 4 and 5
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 5
STARTED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Treatment Period 5
COMPLETED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Treatment Period 5
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Between Periods 5 and 6
STARTED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Washout Between Periods 5 and 6
COMPLETED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Washout Between Periods 5 and 6
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 6
STARTED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Treatment Period 6
COMPLETED
|
5
|
5
|
4
|
5
|
4
|
6
|
|
Treatment Period 6
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1
Abediterol dry powder inhaler (DPI) 0.156 μg, followed by Abediterol pressurised metered-dose inhaler (pMDI) 0.05 μg; Placebo; Abediterol pMDI 0.156 μg; Abediterol DPI 2.5 μg; Abediterol pMDI 2.5 μg
|
Sequence 2
Abediterol pressurised metered-dose inhaler (pMDI) 0.05 μg, followed by Abediterol pMDI 0.156 μg; Abediterol dry powder inhaler (DPI) 0.156 μg; Abediterol pMDI 2.5 μg; Placebo; Abediterol DPI 2.5 μg
|
Sequence 3
Abediterol pressurised metered-dose inhaler (pMDI) 0.156 μg, followed by Abediterol pMDI 2.5 μg; Abediterol pMDI 0.05 μg; Abediterol dry powder inhaler (DPI) 2.5 μg; Abediterol DPI 0.156 μg; Placebo
|
Sequence 4
Abediterol dry powder inhaler (DPI) 2.5 μg, followed by Placebo; Abediterol pressurised metered-dose inhaler (pMDI) 2.5 μg; Abediterol DPI 0.156 μg; Abediterol pMDI 0.156 μg; Abediterol pMDI 0.05 μg
|
Sequence 5
Abediterol pressurised metered-dose inhaler (pMDI) 2.5 μg, followed by Abediterol dry powder inhaler (DPI) 2.5 μg; Abediterol pMDI 0.156 μg; Placebo; Abediterol pMDI 0.05 μg; Abediterol DPI 0.156 μg
|
Sequence 6
Placebo, followed by Abediterol dry powder inhaler (DPI) 0.156 μg; Abediterol DPI 2.5 μg; Abediterol pressurised metered-dose inhaler (pMDI) 0.05 μg; Abediterol pMDI 2.5 μg; Abediterol pMDI 0.156 μg
|
|---|---|---|---|---|---|---|
|
Washout Between Periods 3 and 4
Protocol Violation
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Single Dose PD & PK Study With Two Formulations of Abediterol in Patients With Asthma
Baseline characteristics by cohort
| Measure |
Overall Study Population
n=30 Participants
|
|---|---|
|
Age, Continuous
|
54.2 Years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
|
Sex/Gender, Customized
Female
|
10 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1).
|
0.225 Liters
Standard Deviation 0.192
|
0.400 Liters
Standard Deviation 0.269
|
0.108 Liters
Standard Deviation 0.212
|
0.170 Liters
Standard Deviation 0.207
|
0.407 Liters
Standard Deviation 0.240
|
-0.001 Liters
Standard Deviation 0.244
|
SECONDARY outcome
Timeframe: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1.
|
72.41 Percentage of participants
|
82.76 Percentage of participants
|
56.67 Percentage of participants
|
73.33 Percentage of participants
|
90.00 Percentage of participants
|
24.14 Percentage of participants
|
SECONDARY outcome
Timeframe: 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Time to Peak FEV1 at Day 1
|
3.7 Hours
Standard Deviation 1.8
|
3.3 Hours
Standard Deviation 1.8
|
3.0 Hours
Standard Deviation 1.9
|
3.5 Hours
Standard Deviation 1.7
|
3.6 Hours
Standard Deviation 2.0
|
2.9 Hours
Standard Deviation 2.2
|
SECONDARY outcome
Timeframe: 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.
Observed maximum concentration (Cmax) of Abediterol, taken directly from the individual concentration-time curve.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=3 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=6 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Observed Maximum Concentration of Abediterol (Cmax)
|
0.2299 pg/mL
Geometric Coefficient of Variation 117.3
|
1.092 pg/mL
Geometric Coefficient of Variation 47.34
|
—
|
0.2460 pg/mL
Geometric Coefficient of Variation 128.7
|
1.211 pg/mL
Geometric Coefficient of Variation 82.21
|
—
|
SECONDARY outcome
Timeframe: 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.
Time to maximum concentration (Tmax) of Abediterol (h), taken directly from the individual concentration-time curve.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=3 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=6 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Time (h) to Maximum Concentration of Abediterol (Tmax).
|
0.980 Hours
Interval 0.23 to 1.0
|
0.500 Hours
Interval 0.23 to 1.0
|
—
|
0.735 Hours
Interval 0.48 to 35.6
|
0.620 Hours
Interval 0.07 to 12.0
|
—
|
SECONDARY outcome
Timeframe: 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.
Terminal rate constant (λz) of Abediterol, estimated by log-linear least square regression of the terminal part of the concentration-time curve.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=23 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=21 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Terminal Rate Constant of Abediterol (λz)
|
—
|
0.0526 l/hour
Standard Deviation 0.0228
|
—
|
—
|
0.0640 l/hour
Standard Deviation 0.0201
|
—
|
SECONDARY outcome
Timeframe: 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.
Terminal half-life (h), estimated as (ln2)/λz (t1/2λz).
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=23 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=21 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Terminal Half-life (h) of Abediterol (t½λz)
|
—
|
14.99 Hours
Standard Deviation 4.827
|
—
|
—
|
11.85 Hours
Standard Deviation 3.533
|
—
|
SECONDARY outcome
Timeframe: 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.
Area under the plasma concentration-curve of Abediterol from time zero to the time of last quantifiable analyte concentration.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
AUClast of Abediterol
|
—
|
9.092 pg.h/mL
Geometric Coefficient of Variation 53.95
|
—
|
—
|
7.674 pg.h/mL
Geometric Coefficient of Variation 132.5
|
—
|
SECONDARY outcome
Timeframe: 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.
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).
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=23 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=21 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
AUC of Abediterol.
|
—
|
12.73 pg.h/mL
Geometric Coefficient of Variation 43.26
|
—
|
—
|
11.08 pg.h/mL
Geometric Coefficient of Variation 50.01
|
—
|
SECONDARY outcome
Timeframe: 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
Apparent plasma clearance for parent drug estimated as dose divided by AUC (CL/F).
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=23 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=21 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Apparent Plasma Clearance for Abediterol (CL/F).
|
—
|
196.4 L/h
Geometric Coefficient of Variation 43.26
|
—
|
—
|
225.6 L/h
Geometric Coefficient of Variation 50.01
|
—
|
SECONDARY outcome
Timeframe: 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
Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz (Vz/F).
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=23 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=21 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Apparent Volume of Distribution for Abediterol at Terminal Phase (Vz/F).
|
—
|
4008 Liters
Geometric Coefficient of Variation 37.41
|
—
|
—
|
3690 Liters
Geometric Coefficient of Variation 49.93
|
—
|
SECONDARY outcome
Timeframe: 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
Mean residence time (h), calculated by AUMC/AUC, where AUMC is the area under the first moment-time curve (MRT).
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=23 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=21 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Mean Residence Time (MRT) of Abediterol.
|
—
|
19.73 Hours
Geometric Coefficient of Variation 35.48
|
—
|
—
|
15.59 Hours
Geometric Coefficient of Variation 29.57
|
—
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Number of Participants With Any Treatment-emergent Adverse Event
|
7 Number of participants
|
10 Number of participants
|
7 Number of participants
|
6 Number of participants
|
7 Number of participants
|
12 Number of participants
|
SECONDARY outcome
Timeframe: Up to last treatment visit (Day 112)Population: All randomised participants who received at least one dose of investigational product
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QTcB interval >450-<=480msec(Day 1,1h)
|
2 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QT interval >450-<=480msec(Day 1,1h)
|
2 Participants
|
1 Participants
|
2 Participants
|
4 Participants
|
2 Participants
|
3 Participants
|
|
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
|
3 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
4 Participants
|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QT interval >450-<=480msec(Day 1,4h)
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QTcB interval >450-<=480msec(Day 2,24h)
|
0 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QTcF interval >450-<=480msec(Day 1,1h)
|
0 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QTcF interval >450-<=480msec(Day 2,24h)
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
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
|
3 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QT interval BL incr. >60msec(Day 1,4h)
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QT interval >450-<=480msec(Day 2,24h)
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
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
|
1 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QTcB interval >450-<=480msec(Day 1,4h)
|
1 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
|
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
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
QTcF interval >450-<=480msec(Day 1,4h)
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
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
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
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
|
2 Participants
|
0 Participants
|
4 Participants
|
1 Participants
|
2 Participants
|
|
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
|
1 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Time to Peak FVC at Day 1
|
2.8 Hours
Standard Deviation 1.8
|
2.3 Hours
Standard Deviation 1.9
|
2.8 Hours
Standard Deviation 2.2
|
3.2 Hours
Standard Deviation 2.3
|
3.4 Hours
Standard Deviation 2.2
|
1.9 Hours
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1.
|
31.03 Percentage of patients
|
72.41 Percentage of patients
|
23.33 Percentage of patients
|
26.67 Percentage of patients
|
76.67 Percentage of patients
|
10.34 Percentage of patients
|
SECONDARY outcome
Timeframe: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Peak FEV1.
|
0.4232 Liters
Standard Error 0.0487
|
0.6018 Liters
Standard Error 0.0487
|
0.2930 Liters
Standard Error 0.0483
|
0.4280 Liters
Standard Error 0.0482
|
0.6266 Liters
Standard Error 0.0483
|
0.1880 Liters
Standard Error 0.0486
|
SECONDARY outcome
Timeframe: 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 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=28 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Normalised FEV1 AUC0-24.
|
0.2767 Liters
Standard Error 0.0468
|
0.4813 Liters
Standard Error 0.0468
|
0.0933 Liters
Standard Error 0.0465
|
0.2091 Liters
Standard Error 0.0464
|
0.4635 Liters
Standard Error 0.0464
|
0.0124 Liters
Standard Error 0.0472
|
SECONDARY outcome
Timeframe: 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 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=28 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Normalised FEV1 AUC0-12.
|
0.3194 Liters
Standard Error 0.0504
|
0.5135 Liters
Standard Error 0.0504
|
0.1575 Liters
Standard Error 0.0500
|
0.2770 Liters
Standard Error 0.0500
|
0.5104 Liters
Standard Error 0.0500
|
0.0629 Liters
Standard Error 0.0507
|
SECONDARY outcome
Timeframe: 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 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Normalised FEV1 AUC0-6.
|
0.3198 Liters
Standard Error 0.0485
|
0.5044 Liters
Standard Error 0.0485
|
0.1646 Liters
Standard Error 0.0481
|
0.2987 Liters
Standard Error 0.0480
|
0.5127 Liters
Standard Error 0.0481
|
0.0654 Liters
Standard Error 0.0484
|
SECONDARY outcome
Timeframe: 45 mins and 15 mins predose, and 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=29 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=27 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Normalised FEV1 AUC12-24.
|
0.2339 Liters
Standard Error 0.0479
|
0.4479 Liters
Standard Error 0.0479
|
0.0504 Liters
Standard Error 0.0479
|
0.1421 Liters
Standard Error 0.0474
|
0.4169 Liters
Standard Error 0.0474
|
-0.0346 Liters
Standard Error 0.0487
|
SECONDARY outcome
Timeframe: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Peak FVC.
|
0.3478 Liters
Standard Error 0.0553
|
0.4932 Liters
Standard Error 0.0552
|
0.2867 Liters
Standard Error 0.0550
|
0.3756 Liters
Standard Error 0.0548
|
0.5059 Liters
Standard Error 0.0549
|
0.2347 Liters
Standard Error 0.0552
|
SECONDARY outcome
Timeframe: 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Trough FVC.
|
0.1702 Liters
Standard Error 0.0523
|
0.3023 Liters
Standard Error 0.0523
|
0.0931 Liters
Standard Error 0.0519
|
0.1218 Liters
Standard Error 0.0517
|
0.3134 Liters
Standard Error 0.0518
|
0.0077 Liters
Standard Error 0.0523
|
SECONDARY outcome
Timeframe: 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 1Population: All randomised participants who received investigational product, irrespective of protocol adherence and continued participation in the study
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.
Outcome measures
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 Participants
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 Participants
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 Participants
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 Participants
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 Participants
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=28 Participants
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Normalised FVC AUC0-24.
|
0.2057 Liters
Standard Error 0.0513
|
0.3646 Liters
Standard Error 0.0512
|
0.0704 Liters
Standard Error 0.0510
|
0.1445 Liters
Standard Error 0.0508
|
0.3409 Liters
Standard Error 0.0509
|
0.0309 Liters
Standard Error 0.0517
|
Adverse Events
Abediterol Dry Powder Inhaler 0.156 μg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Abediterol Dry Powder Inhaler 2.5 μg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Abediterol Pressurised Metered-dose Inhaler 2.5μg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Abediterol Dry Powder Inhaler 0.156 μg
n=29 participants at risk
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
|
Abediterol Dry Powder Inhaler 2.5 μg
n=29 participants at risk
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
|
Abediterol Pressurised Metered-dose Inhaler 0.05μg
n=30 participants at risk
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
n=30 participants at risk
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
|
Abediterol Pressurised Metered-dose Inhaler 2.5μg
n=30 participants at risk
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
|
Placebo
n=29 participants at risk
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/29 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
0.00%
0/29 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
6.7%
2/30 • Number of events 3 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
0.00%
0/30 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
0.00%
0/30 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
0.00%
0/29 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/29 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
3.4%
1/29 • Number of events 1 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
3.3%
1/30 • Number of events 1 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
6.7%
2/30 • Number of events 2 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
0.00%
0/30 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
0.00%
0/29 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/29 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
3.4%
1/29 • Number of events 1 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
0.00%
0/30 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
0.00%
0/30 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
0.00%
0/30 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
6.9%
2/29 • Number of events 2 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
|
Nervous system disorders
Headache
|
10.3%
3/29 • Number of events 3 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
6.9%
2/29 • Number of events 2 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
10.0%
3/30 • Number of events 6 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
10.0%
3/30 • Number of events 3 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
10.0%
3/30 • Number of events 4 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
20.7%
6/29 • Number of events 7 • From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.
The safety analysis set consisted of all randomised subjects who received at least one dose of investigational product.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Publication of the results by the Principal Investigator (PI) will be subject to mutual agreement between the PI and the sponsor.
- Publication restrictions are in place
Restriction type: OTHER