Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease (COPD), safety, inhalation, long-acting muscarinic receptor antagonist (LAMA)
Brief summary
The purpose of this study is to investigate effects of inhaled AZD8683 compared to placebo in COPD patients.
Detailed description
A double-blind, placebo-controlled, randomised, multi-centre, 3-way cross-over, single-dose phase II study to investigate the local and systemic effects of inhaled AZD8683 in patients with chronic obstructive pulmonary disease (COPD)
Interventions
DRUGAZD8683, 50 mcg
Dry powder for inhalation, single dose
DRUGPlacebo
Dry powder for inhalation, single dose
DRUGAZD8683, 200 mcg
Dry powder for inhalation, single dose
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of COPD * Current or ex-smokers * FEV1 40 - 80% of the predicted normal value (post-bronchodilator) and post-bronchodilator FEV1/FVC \< 70%
Exclusion criteria
* Any clinically significant disease or disorder * Any clinically relevant abnormal findings at screening examinations * Family history or presence of glaucoma * Need of long term oxygen therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 0, 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h | Maximum FEV1 value |
| Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | 22 h, 24 h, 26 h | Trough FEV1 value |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 0, 30 min, 2 h, 4 h | Average systolic blood pressure value |
| Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 0, 30 min, 2 h, 4 h | Average diastolic blood pressure value |
| Pulse, Average Effect Over 0 - 4 Hours Post-dose | 0, 30 min, 2 h, 4 h | Average pulse value |
| Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post-dose | 0, 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h | Average FEV1 value |
| QTcF, Average Effect Over 0 - 4 Hours Post-dose | 0, 30 min, 2 h, 4 h | Average QTcF value. QTcF = QT interval corrected for heart rate using Fridericia's formula |
| Plasma AZD8683 Cmax | 0, 5 min, 15 min, 30 min, 45 min, 1 h, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h | Maximum plasma concentration of AZD8683 |
| Plasma AZD8683 AUC0-24 | 0, 5 min, 15 min, 30 min, 45 min, 1 h, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h | Area under the AZD8683 plasma concentration curve from 0 to 24 hours |
| Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 0, 30 min, 2 h, 4 h | Average heart rate value |
| Forced Vital Capacity (FVC), Peak Effect Over 0 - 24 Hours Post-dose | 0, 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h | Maximum FVC value |
Countries
Poland
Participant flow
Recruitment details
The study has been performed at four centers in Poland. The first subject entered the study on 10 October 2010 and the last subject completed the study on 17 December 2010. The randomised population consisted of 28 patients, 27 completed the study. All patients were included in the analysis of all variables.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all groups randomized to one of 6 sequences of drug or placebo. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 4 - Washout | Eligibility criteria not fulfilled | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 63.2 years |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 28 | 0 / 28 | 0 / 27 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 27 |
Outcome results
Primary
Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose
Trough FEV1 value
Time frame: 22 h, 24 h, 26 h
Population: Of the 28 randomised patients, 27 completed the study and one discontinued during the last washout period. All 28 randomised patients were included in the analyses of all variables
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8683 50 mcg | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | 1.53 L | Standard Deviation 0.46 |
| AZD8683 200 mcg | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | 1.60 L | Standard Deviation 0.46 |
| Placebo | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | 1.49 L | Standard Deviation 0.46 |
Primary
Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose
Maximum FEV1 value
Time frame: 0, 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h
Population: Of the 28 randomised patients, 27 completed the study and one discontinued during the last washout period. All 28 randomised patients were included in the analyses of all variables
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8683 50 mcg | Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 1.67 L | Standard Deviation 0.48 |
| AZD8683 200 mcg | Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 1.73 L | Standard Deviation 0.47 |
| Placebo | Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 1.64 L | Standard Deviation 0.47 |
Secondary
Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose
Average diastolic blood pressure value
Time frame: 0, 30 min, 2 h, 4 h
Population: Of the 28 randomised patients, 27 completed the study and one discontinued during the last washout period. All 28 randomised patients were included in the analyses of all variables
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8683 50 mcg | Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 77.9 mmHg | Standard Deviation 7.6 |
| AZD8683 200 mcg | Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 77.5 mmHg | Standard Deviation 6.5 |
| Placebo | Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 77.7 mmHg | Standard Deviation 7.9 |
Secondary
Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post-dose
Average FEV1 value
Time frame: 0, 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h
Population: Of the 28 randomised patients, 27 completed the study and one discontinued during the last washout period. All 28 randomised patients were included in the analyses of all variables
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8683 50 mcg | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post-dose | 1.49 L | Standard Deviation 0.42 |
| AZD8683 200 mcg | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post-dose | 1.54 L | Standard Deviation 0.42 |
| Placebo | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post-dose | 1.44 L | Standard Deviation 0.42 |
Secondary
Forced Vital Capacity (FVC), Peak Effect Over 0 - 24 Hours Post-dose
Maximum FVC value
Time frame: 0, 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h
Population: Of the 28 randomised patients, 27 completed the study and one discontinued during the last washout period. All 28 randomised patients were included in the analyses of all variables
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8683 50 mcg | Forced Vital Capacity (FVC), Peak Effect Over 0 - 24 Hours Post-dose | 3.35 L | Standard Deviation 0.87 |
| AZD8683 200 mcg | Forced Vital Capacity (FVC), Peak Effect Over 0 - 24 Hours Post-dose | 3.39 L | Standard Deviation 0.81 |
| Placebo | Forced Vital Capacity (FVC), Peak Effect Over 0 - 24 Hours Post-dose | 3.28 L | Standard Deviation 0.78 |
Secondary
Heart Rate, Average Effect Over 0 - 4 Hours Post-dose
Average heart rate value
Time frame: 0, 30 min, 2 h, 4 h
Population: Of the 28 randomised patients, 27 completed the study and one discontinued during the last washout period. All 28 randomised patients were included in the analyses of all variables
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8683 50 mcg | Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 76.2 bpm | Standard Deviation 12.1 |
| AZD8683 200 mcg | Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 75.0 bpm | Standard Deviation 13.4 |
| Placebo | Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 72.8 bpm | Standard Deviation 11.4 |
Secondary
Plasma AZD8683 AUC0-24
Area under the AZD8683 plasma concentration curve from 0 to 24 hours
Time frame: 0, 5 min, 15 min, 30 min, 45 min, 1 h, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h
Population: Plasma concentrations were below the LLOQ for all post-dose samples for some patients and treatments. PK parameters for these 3 treatments have been set to missing and are not included in the descriptive statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD8683 50 mcg | Plasma AZD8683 AUC0-24 | 0.1872 nmol*h/L |
| AZD8683 200 mcg | Plasma AZD8683 AUC0-24 | 0.8427 nmol*h/L |
Secondary
Plasma AZD8683 Cmax
Maximum plasma concentration of AZD8683
Time frame: 0, 5 min, 15 min, 30 min, 45 min, 1 h, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h
Population: Plasma concentrations were below the LLOQ for all post-dose samples for some patients and treatments. PK parameters for these 3 treatments have been set to missing and are not included in the descriptive statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD8683 50 mcg | Plasma AZD8683 Cmax | 0.0578 nmol/L |
| AZD8683 200 mcg | Plasma AZD8683 Cmax | 0.2791 nmol/L |
Secondary
Pulse, Average Effect Over 0 - 4 Hours Post-dose
Average pulse value
Time frame: 0, 30 min, 2 h, 4 h
Population: Of the 28 randomised patients, 27 completed the study and one discontinued during the last washout period. All 28 randomised patients were included in the analyses of all variables
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8683 50 mcg | Pulse, Average Effect Over 0 - 4 Hours Post-dose | 77.3 bpm | Standard Deviation 10.5 |
| AZD8683 200 mcg | Pulse, Average Effect Over 0 - 4 Hours Post-dose | 76.0 bpm | Standard Deviation 11.9 |
| Placebo | Pulse, Average Effect Over 0 - 4 Hours Post-dose | 74.9 bpm | Standard Deviation 9.5 |
Secondary
QTcF, Average Effect Over 0 - 4 Hours Post-dose
Average QTcF value. QTcF = QT interval corrected for heart rate using Fridericia's formula
Time frame: 0, 30 min, 2 h, 4 h
Population: Of the 28 randomised patients, 27 completed the study and one discontinued during the last washout period. All 28 randomised patients were included in the analyses of all variables
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8683 50 mcg | QTcF, Average Effect Over 0 - 4 Hours Post-dose | 412.8 ms | Standard Deviation 22.4 |
| AZD8683 200 mcg | QTcF, Average Effect Over 0 - 4 Hours Post-dose | 409.1 ms | Standard Deviation 23.7 |
| Placebo | QTcF, Average Effect Over 0 - 4 Hours Post-dose | 411.9 ms | Standard Deviation 22 |
Secondary
Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose
Average systolic blood pressure value
Time frame: 0, 30 min, 2 h, 4 h
Population: Of the 28 randomised patients, 27 completed the study and one discontinued during the last washout period. All 28 randomised patients were included in the analyses of all variables
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8683 50 mcg | Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 130.7 mmHg | Standard Deviation 14.1 |
| AZD8683 200 mcg | Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 131.2 mmHg | Standard Deviation 12 |
| Placebo | Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 132.2 mmHg | Standard Deviation 13.3 |