Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease (COPD), efficacy, safety, inhalation, long-acting muscarinic receptor antagonist (LAMA)
Brief summary
Chronic Obstructive Pulmonary Disease (COPD) is a chronic respiratory condition with deteriorating lung function over the years. Patients with COPD experience symptoms of shortness of breath, cough and sputum production. This study is to assess the treatment effects after inhalation of three different single doses of AZD9164 (100, 400 and 1200 mcg) and one single dose of tiotropium (18 mcg). One dose of placebo will be given as comparator. 25 patients are to participate in the study and all will be recruited in Sweden. Each patient will visit the study doctor 9 times during the study, whereof 5 visits will be overnight visits. All examinations, treatment and the follow-up is free of charge.
Interventions
DRUGAZD9164
Solution for inhalation through nebulization, single dose
DRUGTiotropium
Dry powder for inhalation, single dose
DRUGPlacebo
Placebo
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A clinical diagnosis of COPD * FEV1 40 - 80% of the predicted normal value (post-bronchodilator) and post- bronchodilator FEV1/FVC \< 70%
Exclusion criteria
* Any clinically relevant abnormal findings at screening examinations * Any clinically significant disease or disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 0, 15 min, 30 min, 60 min, 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, 15 min, 30 min, 60 min, 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 |
| Plasma AZD9164 Cmax | 0, 5 min, 15 min, 30 min, 60 min, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h | Maximum plasma concentration of AZD9164 |
| Plasma AZD9164 AUC0-24 | 0, 5 min, 15 min, 30 min, 60 min, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h | Area under the AZD9164 plasma concentration curve |
| Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 0, 30 min, 2 h, 4 h | Average heart rate value |
| Forced Expiratory Volume in One Second (FEV1), Effect at 15 Minutes Post-dose | 15 min | 15 min FEV1 value |
Countries
Sweden
Participant flow
Recruitment details
The study has been performed at four centers in Sweden. The first subject entered the study on 23 June 2009 and the last subject completed the study on 6 November 2009.
Participants by arm
| Arm | Count |
|---|---|
| Overall Number of Baseline Participants | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | Overall Number of Baseline Participants |
|---|---|
| Age Continuous | 64.2 years |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 28 | 15 / 28 | 27 / 28 | 2 / 28 | 3 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | 1.58 L | Standard Deviation 0.38 |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | 1.63 L | Standard Deviation 0.38 |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | 1.62 L | Standard Deviation 0.38 |
| Spiriva 18 Mcg First, Then Placebo for AZD9164 | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | 1.57 L | Standard Deviation 0.35 |
| Placebo for Spiriva First, Then Placebo for AZD9164 | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | 1.52 L | Standard Deviation 0.39 |
Primary
Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose
Maximum FEV1 value
Time frame: 0, 15 min, 30 min, 60 min, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 1.71 L | Standard Deviation 0.36 |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 1.79 L | Standard Deviation 0.39 |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 1.72 L | Standard Deviation 0.39 |
| Spiriva 18 Mcg First, Then Placebo for AZD9164 | Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 1.71 L | Standard Deviation 0.35 |
| Placebo for Spiriva First, Then Placebo for AZD9164 | Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | 1.63 L | Standard Deviation 0.41 |
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 73.1 mmHg | Standard Deviation 7.9 |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 75.6 mmHg | Standard Deviation 8.2 |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 74.2 mmHg | Standard Deviation 6.7 |
| Spiriva 18 Mcg First, Then Placebo for AZD9164 | Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 74.8 mmHg | Standard Deviation 6.2 |
| Placebo for Spiriva First, Then Placebo for AZD9164 | Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 73.5 mmHg | Standard Deviation 8.6 |
Secondary
Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post Dose
Average FEV1 value
Time frame: 0, 15 min, 30 min, 60 min, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post Dose | 1.57 L | Standard Deviation 0.36 |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post Dose | 1.63 L | Standard Deviation 0.39 |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post Dose | 1.56 L | Standard Deviation 0.38 |
| Spiriva 18 Mcg First, Then Placebo for AZD9164 | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post Dose | 1.58 L | Standard Deviation 0.35 |
| Placebo for Spiriva First, Then Placebo for AZD9164 | Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post Dose | 1.50 L | Standard Deviation 0.4 |
Secondary
Forced Expiratory Volume in One Second (FEV1), Effect at 15 Minutes Post-dose
15 min FEV1 value
Time frame: 15 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Effect at 15 Minutes Post-dose | 1.42 L | Standard Deviation 0.38 |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Effect at 15 Minutes Post-dose | 1.30 L | Standard Deviation 0.42 |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Forced Expiratory Volume in One Second (FEV1), Effect at 15 Minutes Post-dose | 1.25 L | Standard Deviation 0.44 |
| Spiriva 18 Mcg First, Then Placebo for AZD9164 | Forced Expiratory Volume in One Second (FEV1), Effect at 15 Minutes Post-dose | 1.55 L | Standard Deviation 0.36 |
| Placebo for Spiriva First, Then Placebo for AZD9164 | Forced Expiratory Volume in One Second (FEV1), Effect at 15 Minutes Post-dose | 1.49 L | Standard Deviation 0.42 |
Secondary
Heart Rate, Average Effect Over 0 - 4 Hours Post-dose
Average heart rate value
Time frame: 0, 30 min, 2 h, 4 h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 61.0 bpm | Standard Deviation 6.9 |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 62.8 bpm | Standard Deviation 7.8 |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 65.2 bpm | Standard Deviation 7.4 |
| Spiriva 18 Mcg First, Then Placebo for AZD9164 | Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 61.1 bpm | Standard Deviation 7.4 |
| Placebo for Spiriva First, Then Placebo for AZD9164 | Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | 61.3 bpm | Standard Deviation 7.4 |
Secondary
Plasma AZD9164 AUC0-24
Area under the AZD9164 plasma concentration curve
Time frame: 0, 5 min, 15 min, 30 min, 60 min, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Plasma AZD9164 AUC0-24 | 2.90 nmol*h/L |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Plasma AZD9164 AUC0-24 | 15.2 nmol*h/L |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Plasma AZD9164 AUC0-24 | 58.1 nmol*h/L |
Secondary
Plasma AZD9164 Cmax
Maximum plasma concentration of AZD9164
Time frame: 0, 5 min, 15 min, 30 min, 60 min, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Plasma AZD9164 Cmax | 0.529 nmol/L |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Plasma AZD9164 Cmax | 3.629 nmol/L |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Plasma AZD9164 Cmax | 20.02 nmol/L |
Secondary
Pulse, Average Effect Over 0 - 4 Hours Post-dose
Average pulse value
Time frame: 0, 30 min, 2 h, 4 h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Pulse, Average Effect Over 0 - 4 Hours Post-dose | 61.1 bpm | Standard Deviation 7.6 |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Pulse, Average Effect Over 0 - 4 Hours Post-dose | 62.9 bpm | Standard Deviation 7.1 |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Pulse, Average Effect Over 0 - 4 Hours Post-dose | 64.8 bpm | Standard Deviation 8 |
| Spiriva 18 Mcg First, Then Placebo for AZD9164 | Pulse, Average Effect Over 0 - 4 Hours Post-dose | 60.2 bpm | Standard Deviation 7.6 |
| Placebo for Spiriva First, Then Placebo for AZD9164 | Pulse, Average Effect Over 0 - 4 Hours Post-dose | 61.3 bpm | Standard Deviation 7.5 |
Secondary
QTcF, Average Effect Over 0 - 4 Hours Post-dose
Average QTcF value
Time frame: 0, 30 min, 2 h, 4 h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | QTcF, Average Effect Over 0 - 4 Hours Post-dose | 400 ms | Standard Deviation 23.1 |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | QTcF, Average Effect Over 0 - 4 Hours Post-dose | 399 ms | Standard Deviation 25.8 |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | QTcF, Average Effect Over 0 - 4 Hours Post-dose | 396 ms | Standard Deviation 25 |
| Spiriva 18 Mcg First, Then Placebo for AZD9164 | QTcF, Average Effect Over 0 - 4 Hours Post-dose | 401 ms | Standard Deviation 26.8 |
| Placebo for Spiriva First, Then Placebo for AZD9164 | QTcF, Average Effect Over 0 - 4 Hours Post-dose | 398 ms | Standard Deviation 23.1 |
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD9164 100 Mcg First, Then Placebo for Spiriva | Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 125.5 mmHg | Standard Deviation 15.6 |
| AZD9164 400 Mcg First, Then Placebo for Spiriva | Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 127.9 mmHg | Standard Deviation 14.8 |
| AZD9164 1200 Mcg First, Then Placebo for Spiriva | Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 127.3 mmHg | Standard Deviation 14.9 |
| Spiriva 18 Mcg First, Then Placebo for AZD9164 | Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 128.0 mmHg | Standard Deviation 13.3 |
| Placebo for Spiriva First, Then Placebo for AZD9164 | Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | 126.5 mmHg | Standard Deviation 16.6 |