Trial Outcomes & Findings for Efficacy, Pharmacokinetics (PK), Safety and Tolerability Study of Inhaled AZD8871 (NCT NCT02971293)

NCT ID: NCT02971293

Last Updated: 2019-06-18

Results Overview

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 15

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

On Day 15

Results posted on

2019-06-18

Participant Flow

This study was conducted at two centres, one each in Germany and the UK. The first patient was enrolled in December 2016 and the last patient last visit was in August 2017.

A total of 103 patients were screened; 42 patients were eligible to participate and were randomised.

Participant milestones

Participant milestones
Measure
All Participants
All subjects received AZD8871 100 µg, AZD8871 600 µg or placebo, once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products. Each subject was randomized to one of three sequences in a 3-way, complete crossover William's design, and received all 3 treatments in turn, in three 14-day treatment periods, each (except the last one) followed by a wash-out period of 28-35 days.
Overall Study
STARTED
42
Overall Study
COMPLETED
31
Overall Study
NOT COMPLETED
11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy, Pharmacokinetics (PK), Safety and Tolerability Study of Inhaled AZD8871

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Overall Study Population
n=42 Participants
Full analysis set: All randomised participants who received at least one dose of investigational product.
Age, Continuous
63.6 Years
STANDARD_DEVIATION 6.6 • n=5 Participants
Sex/Gender, Customized
Female
14 Participants
n=5 Participants
Sex/Gender, Customized
Male
28 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
42 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: On Day 15

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 15

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)
0.168 L
Standard Error 0.037
0.267 L
Standard Error 0.035
0.007 L
Standard Error 0.036

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 1 of each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Single Dose)
AZD8871
61.05 pg/mL
Geometric Coefficient of Variation 47.47
290.8 pg/mL
Geometric Coefficient of Variation 36.30
Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Single Dose)
LAS191861
7.796 pg/mL
Geometric Coefficient of Variation 38.67
33.87 pg/mL
Geometric Coefficient of Variation 33.05
Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Single Dose)
LAS34850
187.7 pg/mL
Geometric Coefficient of Variation 55.41
1016 pg/mL
Geometric Coefficient of Variation 50.72

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 14 of each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
AZD8871
72.52 pg/mL
Geometric Coefficient of Variation 45.69
381.8 pg/mL
Geometric Coefficient of Variation 36.09
Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
LAS191861
11.89 pg/mL
Geometric Coefficient of Variation 39.41
63.17 pg/mL
Geometric Coefficient of Variation 38.23
Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
LAS34850
221.4 pg/mL
Geometric Coefficient of Variation 69.96
1152 pg/mL
Geometric Coefficient of Variation 55.11

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 1 of each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Single Dose)
AZD8871
0.93 h
Interval 0.42 to 2.0
1.46 h
Interval 0.48 to 2.03
Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Single Dose)
LAS191861
1.92 h
Interval 0.93 to 4.83
2.02 h
Interval 1.0 to 4.03
Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Single Dose)
LAS34850
3.94 h
Interval 1.92 to 6.0
3.98 h
Interval 3.92 to 6.03

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 14 of each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
AZD8871
0.93 h
Interval 0.42 to 1.0
1.00 h
Interval 0.5 to 2.22
Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
LAS191861
1.96 h
Interval 0.98 to 3.95
2.00 h
Interval 0.98 to 3.98
Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
LAS34850
3.92 h
Interval 0.0 to 4.0
4.02 h
Interval 3.9 to 6.05

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 1 of each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
AUClast of AZD8871 and Its Metabolites (Single Dose)
AZD8871
301.0 pg*h/mL
Geometric Coefficient of Variation 54.52
1777 pg*h/mL
Geometric Coefficient of Variation 40.93
AUClast of AZD8871 and Its Metabolites (Single Dose)
LAS191861
60.06 pg*h/mL
Geometric Coefficient of Variation 94.87
358.5 pg*h/mL
Geometric Coefficient of Variation 32.60
AUClast of AZD8871 and Its Metabolites (Single Dose)
LAS34850
1414 pg*h/mL
Geometric Coefficient of Variation 69.31
9299 pg*h/mL
Geometric Coefficient of Variation 53.88

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 14 of each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
AUClast of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
AZD8871
539.2 pg*h/mL
Geometric Coefficient of Variation 51.23
3156 pg*h/mL
Geometric Coefficient of Variation 42.51
AUClast of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
LAS191861
160.2 pg*h/mL
Geometric Coefficient of Variation 64.39
935.9 pg*h/mL
Geometric Coefficient of Variation 46.56
AUClast of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
LAS34850
1964 pg*h/mL
Geometric Coefficient of Variation 93.81
13050 pg*h/mL
Geometric Coefficient of Variation 52.49

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 1 of each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
AUC0-24 of AZD8871 and Its Metabolites (Single Dose)
AZD8871
326.1 pg*h/mL
Geometric Coefficient of Variation 49.18
1776 pg*h/mL
Geometric Coefficient of Variation 40.95
AUC0-24 of AZD8871 and Its Metabolites (Single Dose)
LAS191861
135.6 pg*h/mL
Geometric Coefficient of Variation 25.79
358.1 pg*h/mL
Geometric Coefficient of Variation 32.56
AUC0-24 of AZD8871 and Its Metabolites (Single Dose)
LAS34850
0 pg*h/mL
Geometric Coefficient of Variation 0
10440 pg*h/mL
Geometric Coefficient of Variation 49.47

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations

Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 14 of each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
AUC0-24 of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
AZD8871
538.4 pg*h/mL
Geometric Coefficient of Variation 51.16
3152 pg*h/mL
Geometric Coefficient of Variation 42.53
AUC0-24 of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
LAS191861
179.4 pg*h/mL
Geometric Coefficient of Variation 38.81
933.8 pg*h/mL
Geometric Coefficient of Variation 46.65
AUC0-24 of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
LAS34850
3281 pg*h/mL
Geometric Coefficient of Variation 66.13
13030 pg*h/mL
Geometric Coefficient of Variation 52.51

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 14.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Accumulation ratio for Cmax estimated as (Cmax on Day 14 / Cmax on Day 1) in each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Accumulation Ratio for Cmax (RacCmax) of AZD8871 and Its Metabolites (Day 14)
AZD8871
1.263 pg/mL
Interval 0.765 to 2.3
1.385 pg/mL
Interval 0.7 to 1.9
Accumulation Ratio for Cmax (RacCmax) of AZD8871 and Its Metabolites (Day 14)
LAS191861
1.594 pg/mL
Interval 0.946 to 2.86
1.968 pg/mL
Interval 0.929 to 2.74
Accumulation Ratio for Cmax (RacCmax) of AZD8871 and Its Metabolites (Day 14)
LAS34850
1.257 pg/mL
Interval 0.757 to 3.388
1.133 pg/mL
Interval 0.545 to 1.64

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 14.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Accumulation ratio for AUC0-24 estimated as AUC0-24 on Day 14 / AUC0-24 on Day 1 in each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Accumulation Ratio for AUC0-24 (RacAUC[0-24]) of AZD8871 and Its Metabolites (Day 14)
AZD8871
1.893 pg*h/mL
Interval 1.06 to 3.86
1.878 pg*h/mL
Interval 1.09 to 2.87
Accumulation Ratio for AUC0-24 (RacAUC[0-24]) of AZD8871 and Its Metabolites (Day 14)
LAS191861
1.576 pg*h/mL
Interval 1.1 to 2.44
2.721 pg*h/mL
Interval 1.41 to 3.55
Accumulation Ratio for AUC0-24 (RacAUC[0-24]) of AZD8871 and Its Metabolites (Day 14)
LAS34850
1.24 pg*h/mL
Interval 1.24 to 1.24
1.326 pg*h/mL
Interval 0.713 to 1.77

SECONDARY outcome

Timeframe: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.

Population: Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.

Average plasma concentration during a dosing interval calculated on Day 14 of each treatment period.

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=16 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=18 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Cavg of AZD8871 and Its Metabolites During a Dosing Interval (Day 14)
AZD8871
22.44 pg/mL
Geometric Coefficient of Variation 51.13
131.4 pg/mL
Geometric Coefficient of Variation 42.49
Cavg of AZD8871 and Its Metabolites During a Dosing Interval (Day 14)
LAS191861
7.478 pg/mL
Geometric Coefficient of Variation 38.81
38.94 pg/mL
Geometric Coefficient of Variation 46.62
Cavg of AZD8871 and Its Metabolites During a Dosing Interval (Day 14)
LAS34850
136.7 pg/mL
Geometric Coefficient of Variation 66.11
543.3 pg/mL
Geometric Coefficient of Variation 52.44

SECONDARY outcome

Timeframe: on Day 1

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 1

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Trough FEV1 at Day 1 (Single Dose)
0.092 L
Standard Error 0.029
0.161 L
Standard Error 0.027
0.006 L
Standard Error 0.028

SECONDARY outcome

Timeframe: on Day 8 (pre-dose)

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 8 (pre-dose)

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Trough FEV1 at Day 8 (Pre-dose)
0.180 L
Standard Error 0.033
0.232 L
Standard Error 0.030
0.032 L
Standard Error 0.031

SECONDARY outcome

Timeframe: Days 1-15

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 over the treatment duration from Day 1 to Day 15

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Trough FEV1 Over the Treatment Duration (Days 1-15)
0.146 L
Standard Error 0.029
0.215 L
Standard Error 0.027
0.016 L
Standard Error 0.027

SECONDARY outcome

Timeframe: on Day 1

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Peak FEV1 at Day 1 (Single Dose)
0.376 L
Standard Error 0.026
0.469 L
Standard Error 0.025
0.076 L
Standard Error 0.025

SECONDARY outcome

Timeframe: on Day 8

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Peak FEV1 at Day 8
0.486 L
Standard Error 0.040
0.556 L
Standard Error 0.037
0.136 L
Standard Error 0.038

SECONDARY outcome

Timeframe: on Day 14

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Peak FEV1 at Day 14
0.476 L
Standard Error 0.037
0.522 L
Standard Error 0.035
0.095 L
Standard Error 0.036

SECONDARY outcome

Timeframe: over the treatment duration (Days 1-15)

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Peak FEV1 Over the Treatment Duration (Days 1-15)
0.438 L
Standard Error 0.028
0.511 L
Standard Error 0.027
0.102 L
Standard Error 0.028

SECONDARY outcome

Timeframe: From Day 1 to Day 8 post-treatment

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire. The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in BCSS Questionnaire Total Score From Day 1 to Day 8 Post-treatment
-0.416 Scores on a scale
Standard Error 0.216
-0.920 Scores on a scale
Standard Error 0.198
-0.071 Scores on a scale
Standard Error 0.205

SECONDARY outcome

Timeframe: From Day 9 to Day 14 post-treatment

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire. The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in BCSS Questionnaire Total Score From Day 9 to Day 14 Post-treatment
-0.491 Scores on a scale
Standard Error 0.237
-1.191 Scores on a scale
Standard Error 0.219
-0.030 Scores on a scale
Standard Error 0.226

SECONDARY outcome

Timeframe: From Day 1 to Day 8 post-treatment

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores. On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Cough Individual Domain Score From Day 1 to Day 8 Post-treatment
-0.186 Scores on a scale
Standard Error 0.091
-0.287 Scores on a scale
Standard Error 0.084
-0.134 Scores on a scale
Standard Error 0.087

SECONDARY outcome

Timeframe: From Day 9 to Day 14 post-treatment

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores. On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Cough Individual Domain Score From Day 9 to Day 14 Post-treatment
-0.160 Scores on a scale
Standard Error 0.096
-0.445 Scores on a scale
Standard Error 0.088
-0.123 Scores on a scale
Standard Error 0.091

SECONDARY outcome

Timeframe: From Day 1 to Day 8 post-treatment

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores. On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Breathlessness Individual Domain Score From Day 1 to Day 8 Post-treatment
-0.122 Scores on a scale
Standard Error 0.097
-0.377 Scores on a scale
Standard Error 0.089
0.099 Scores on a scale
Standard Error 0.092

SECONDARY outcome

Timeframe: From Day 9 to Day 14 post-treatment

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores. On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Breathlessness Individual Domain Score From Day 9 to Day 14 Post-treatment
-0.202 Scores on a scale
Standard Error 0.108
-0.453 Scores on a scale
Standard Error 0.100
0.106 Scores on a scale
Standard Error 0.103

SECONDARY outcome

Timeframe: From Day 1 to Day 8 post-treatment

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores. On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Sputum Individual Domain Score From Day 1 to Day 8 Post-treatment
-0.100 Scores on a scale
Standard Error 0.070
-0.255 Scores on a scale
Standard Error 0.064
-0.035 Scores on a scale
Standard Error 0.066

SECONDARY outcome

Timeframe: From Day 9 to Day 14 post-treatment

Population: Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.

The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores. On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).

Outcome measures

Outcome measures
Measure
AZD8871 100 µg
n=34 Participants
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 Participants
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 Participants
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Change From Baseline in Sputum Individual Domain Score From Day 9 to Day 14 Post-treatment
-0.122 Scores on a scale
Standard Error 0.078
-0.297 Scores on a scale
Standard Error 0.073
-0.011 Scores on a scale
Standard Error 0.075

Adverse Events

AZD8871 100 µg

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

AZD8871 600 µg

Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
AZD8871 100 µg
n=34 participants at risk
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 participants at risk
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 participants at risk
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Infections and infestations
Abdominal wall abscess
0.00%
0/34 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
0.00%
0/39 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
2.8%
1/36 • Number of events 1 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
Infections and infestations
Appendicitis
0.00%
0/34 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
0.00%
0/39 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
2.8%
1/36 • Number of events 1 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease exacerbation
0.00%
0/34 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
2.6%
1/39 • Number of events 1 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
0.00%
0/36 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.

Other adverse events

Other adverse events
Measure
AZD8871 100 µg
n=34 participants at risk
The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
AZD8871 600 µg
n=39 participants at risk
The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
Placebo
n=36 participants at risk
The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
5.9%
2/34 • Number of events 2 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
5.1%
2/39 • Number of events 2 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
0.00%
0/36 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
Nervous system disorders
Headache
11.8%
4/34 • Number of events 5 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
7.7%
3/39 • Number of events 3 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
11.1%
4/36 • Number of events 7 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/34 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
5.1%
2/39 • Number of events 2 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
0.00%
0/36 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
Infections and infestations
Viral upper respiratory tract infections
0.00%
0/34 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
0.00%
0/39 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.
5.6%
2/36 • Number of events 2 • From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)
All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed. Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or \>30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.

Additional Information

Dr Ioannis Psallidas, MD, PhD

AstraZeneca

Phone: 1-877-240-9479

Results disclosure agreements

  • Principal investigator is a sponsor employee Publication and / or presentation whether complete or partial, of any part of the data or results of this study will not be allowed until global publication and study results disclosure by the sponsor as per EMA / FDA regulatory compliance obligations, and only after mutual agreement between the Investigator and AstraZeneca
  • Publication restrictions are in place

Restriction type: OTHER