Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Moderate to severe COPD
Brief summary
The purpose of this study is to study histological changes, cellularity, clinical efficacy and safety of AZD1981 in patients with Chronic Obstructive Pulmonary Disease
Interventions
DRUGAZD1981
Oral tablet, twice daily, 4 weeks treatment
DRUGPlacebo
Placebo
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
* Men or women 40 years or above * FEV1 between 40 and 80% of predicted normal value post-bronchodilator * Clinical diagnosis of COPD
Exclusion criteria
* Other clinically relevant disease or disorders * Exacerbation of COPD within 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induced Sputum: Total Cells Count | Before and after 3 week treatment | Change in Induced sputum Total cells count from baseline |
| Induced Sputum: Eosinophil Count (%) | Before and after 3 week treatment | Change in Induced sputum Eosinophil count (% of total) from baseline |
| Aggregated Pathology Score | Before and after 1 month treatment | Composite endpoint subscores: histological grade, immunohistochemistry grade, leucocyte counts. Each subscore measured on scale 1 (normal) to 5 (worst outcome). Composite score summed across the subscores, ranging from 3 (normal) to 15 (worst outcome). Change from baseline. |
| Bronchoalveolar Lavage (BAL): Eosinophil Count (%) | Before and after 1 month treatment | Change in Bronchoalveolar Lavage (BAL): Eosinophil count (% of total) from baseline |
| Bronchoalveolar Lavage (BAL): Neutrophil Count (%) | Before and after 1 month treatment | Change in Bronchoalveolar Lavage (BAL): Neutrophil count (% of total) from baseline |
| Bronchoalveolar Lavage (BAL): Macrophages Count (%) | Before and after 1 month treatment | Change in Bronchoalveolar Lavage (BAL): Macrophages count (% of total) from baseline |
| Bronchoalveolar Lavage (BAL): Lymphocytes Count (%) | Before and after 1 month treatment | Change in Bronchoalveolar Lavage (BAL): Lymphocytes count (% of total) from baseline |
| Bronchoalveolar Lavage (BAL): Epithelial Cells Count (%) | Before and after 1 month treatment | Change in Bronchoalveolar Lavage (BAL): Epithelial cells count (% of total) from baseline |
| Bronchoalveolar Lavage (BAL): Total Cells Count | Before and after 1 month treatment | Change in Bronchoalveolar Lavage (BAL): Total cells count from baseline |
| Induced Sputum: Epithelial Cells Count (%) | Before and after 3 week treatment | Change in Induced sputum Epithelial cells count (% of total) from baseline |
| Induced Sputum: Neutrophils Count (%) | Before and after 3 week treatment | Change in Induced sputum Neutrophils count (% of total) from baseline |
| Induced Sputum: Macrophages Count (%) | Before and after 3 week treatment | Change in Induced sputum Macrophages count (% of total) from baseline |
| Induced Sputum: Lymphocytes Count (%) | Before and after 3 week treatment | Change in Induced sputum Lymphocytes count (% of total) from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Chronic Obstructive Pulmonary Disease (COPD) The Clinical COPD Questionnaire (CCQ) | Before and after 1 month treatment | Change in total CCQ score from baseline to last measurement on treatment. scored on a scale of 0 - 6. 0 =(low symptoms)-6 =(high symptoms) |
| Peak Expiratory Flow (PEF) Morning | Before and after 1 month treatment | Mean change in Peak Expiratory Flow (PEF) morning from baseline to the average of the treatment period |
| Peak Expiratory Flow (PEF) Evening | Before and after 1 month treatment | Mean change in Peak Expiratory Flow (PEF) evening from baseline to the average of the treatment period |
| Chronic Obstructive Pulmonary Disease (COPD) Symptom Night-time Awakenings Score | Before and after 1 month treatment | Mean change in COPD symptom night-time awakening score from baseline to the average of the treatment period. 0=(no symptom)-4=(no sleep) |
| Chronic Obstructive Pulmonary Disease (COPD) Symptom Breathing Score | Before and after 1 month treatment | Mean change in COPD symptom breathing score from baseline to the average of the treatment period. 0= (none) - 4 =(severe). |
| Chronic Obstructive Pulmonary Disease (COPD) Symptom Cough Score | Before and after 1 month treatment | Mean change in COPD symptom cough score from baseline to the average of the treatment period. 0= (none) - 4= (almost constant) |
| Chronic Obstructive Pulmonary Disease (COPD) Symptom Sputum Score | Before and after 1 month treatment | Mean change in COPD symptom sputum score from baseline to the average of the treatment period. 0= (none) - 4= (severe). |
| Adverse Event (AE) | 1 month | Number of participants with an Adverse Event |
| Forced Expiratory Volume in 1 Second (FEV1) | Before and after 1 month treatment | Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to end of treatment |
Countries
Germany, Netherlands, United Kingdom
Participant flow
Recruitment details
84 patients enrolled, 52 were randomised, 1 patient discontinued before treatment start and 51 patients completed the study. First patient entered the study on 17 November 2008 and the last patient finished the study on 10 June 2009.
Participants by arm
| Arm | Count |
|---|---|
| AZD1981 AZD1981 1000 mg, twice daily | 25 |
| Placebo Placebo, twice daily | 26 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | AZD1981 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 61 Years | 61.1 Years | 61 Years |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 16 Participants | 22 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 25 | 7 / 26 |
| serious Total, serious adverse events | 1 / 25 | 0 / 26 |
Outcome results
Primary
Aggregated Pathology Score
Composite endpoint subscores: histological grade, immunohistochemistry grade, leucocyte counts. Each subscore measured on scale 1 (normal) to 5 (worst outcome). Composite score summed across the subscores, ranging from 3 (normal) to 15 (worst outcome). Change from baseline.
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Aggregated Pathology Score | 7.88 Score on a scale | 95% Confidence Interval 7.43 |
| Placebo | Aggregated Pathology Score | 8.15 Score on a scale | 95% Confidence Interval 7.68 |
Primary
Bronchoalveolar Lavage (BAL): Eosinophil Count (%)
Change in Bronchoalveolar Lavage (BAL): Eosinophil count (% of total) from baseline
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Bronchoalveolar Lavage (BAL): Eosinophil Count (%) | -1.58 percentage | 95% Confidence Interval -2.22 |
| Placebo | Bronchoalveolar Lavage (BAL): Eosinophil Count (%) | -1.45 percentage | 95% Confidence Interval -2.13 |
Primary
Bronchoalveolar Lavage (BAL): Epithelial Cells Count (%)
Change in Bronchoalveolar Lavage (BAL): Epithelial cells count (% of total) from baseline
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Bronchoalveolar Lavage (BAL): Epithelial Cells Count (%) | -4.18 percentage | 95% Confidence Interval -11.8 |
| Placebo | Bronchoalveolar Lavage (BAL): Epithelial Cells Count (%) | -2.98 percentage | 95% Confidence Interval -10.98 |
Primary
Bronchoalveolar Lavage (BAL): Lymphocytes Count (%)
Change in Bronchoalveolar Lavage (BAL): Lymphocytes count (% of total) from baseline
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Bronchoalveolar Lavage (BAL): Lymphocytes Count (%) | -1.47 percentage | 95% Confidence Interval -3.04 |
| Placebo | Bronchoalveolar Lavage (BAL): Lymphocytes Count (%) | -0.37 percentage | 95% Confidence Interval -2.02 |
Primary
Bronchoalveolar Lavage (BAL): Macrophages Count (%)
Change in Bronchoalveolar Lavage (BAL): Macrophages count (% of total) from baseline
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Bronchoalveolar Lavage (BAL): Macrophages Count (%) | 9.84 percentage | 95% Confidence Interval -1.51 |
| Placebo | Bronchoalveolar Lavage (BAL): Macrophages Count (%) | 10.68 percentage | 95% Confidence Interval -1.24 |
Primary
Bronchoalveolar Lavage (BAL): Neutrophil Count (%)
Change in Bronchoalveolar Lavage (BAL): Neutrophil count (% of total) from baseline
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Bronchoalveolar Lavage (BAL): Neutrophil Count (%) | -2.24 percentage | 95% Confidence Interval -12.94 |
| Placebo | Bronchoalveolar Lavage (BAL): Neutrophil Count (%) | -5.67 percentage | 95% Confidence Interval -16.75 |
Primary
Bronchoalveolar Lavage (BAL): Total Cells Count
Change in Bronchoalveolar Lavage (BAL): Total cells count from baseline
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Bronchoalveolar Lavage (BAL): Total Cells Count | 0.02 10^6/g | 95% Confidence Interval -0.1 |
| Placebo | Bronchoalveolar Lavage (BAL): Total Cells Count | 0.04 10^6/g | 95% Confidence Interval -0.1 |
Primary
Induced Sputum: Eosinophil Count (%)
Change in Induced sputum Eosinophil count (% of total) from baseline
Time frame: Before and after 3 week treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Induced Sputum: Eosinophil Count (%) | -2.14 percentage | 95% Confidence Interval -3.3 |
| Placebo | Induced Sputum: Eosinophil Count (%) | -0.81 percentage | 95% Confidence Interval -1.92 |
Primary
Induced Sputum: Epithelial Cells Count (%)
Change in Induced sputum Epithelial cells count (% of total) from baseline
Time frame: Before and after 3 week treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Induced Sputum: Epithelial Cells Count (%) | -0.50 percentage | 95% Confidence Interval -6.01 |
| Placebo | Induced Sputum: Epithelial Cells Count (%) | 4.11 percentage | 95% Confidence Interval -1.04 |
Primary
Induced Sputum: Lymphocytes Count (%)
Change in Induced sputum Lymphocytes count (% of total) from baseline
Time frame: Before and after 3 week treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Induced Sputum: Lymphocytes Count (%) | -0.01 percentage | 95% Confidence Interval -0.21 |
| Placebo | Induced Sputum: Lymphocytes Count (%) | 0.02 percentage | 95% Confidence Interval -0.17 |
Primary
Induced Sputum: Macrophages Count (%)
Change in Induced sputum Macrophages count (% of total) from baseline
Time frame: Before and after 3 week treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Induced Sputum: Macrophages Count (%) | 1.31 percentage | 95% Confidence Interval -11.95 |
| Placebo | Induced Sputum: Macrophages Count (%) | -7.79 percentage | 95% Confidence Interval -20.27 |
Primary
Induced Sputum: Neutrophils Count (%)
Change in Induced sputum Neutrophils count (% of total) from baseline
Time frame: Before and after 3 week treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Induced Sputum: Neutrophils Count (%) | 0.70 percentage | 95% Confidence Interval -12.79 |
| Placebo | Induced Sputum: Neutrophils Count (%) | 3.73 percentage | 95% Confidence Interval -8.84 |
Primary
Induced Sputum: Total Cells Count
Change in Induced sputum Total cells count from baseline
Time frame: Before and after 3 week treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Induced Sputum: Total Cells Count | -1.07 10^6/g | 95% Confidence Interval -3.21 |
| Placebo | Induced Sputum: Total Cells Count | -1.69 10^6/g | 95% Confidence Interval -4.07 |
Secondary
Adverse Event (AE)
Number of participants with an Adverse Event
Time frame: 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD1981 | Adverse Event (AE) | 17 Participants |
| Placebo | Adverse Event (AE) | 14 Participants |
Secondary
Chronic Obstructive Pulmonary Disease (COPD) Symptom Breathing Score
Mean change in COPD symptom breathing score from baseline to the average of the treatment period. 0= (none) - 4 =(severe).
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Chronic Obstructive Pulmonary Disease (COPD) Symptom Breathing Score | -0.25 Score on a scale | 95% Confidence Interval -0.47 |
| Placebo | Chronic Obstructive Pulmonary Disease (COPD) Symptom Breathing Score | -0.21 Score on a scale | 95% Confidence Interval -0.45 |
Secondary
Chronic Obstructive Pulmonary Disease (COPD) Symptom Cough Score
Mean change in COPD symptom cough score from baseline to the average of the treatment period. 0= (none) - 4= (almost constant)
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Chronic Obstructive Pulmonary Disease (COPD) Symptom Cough Score | -0.39 Score on a scale | 95% Confidence Interval -0.63 |
| Placebo | Chronic Obstructive Pulmonary Disease (COPD) Symptom Cough Score | -0.35 Score on a scale | 95% Confidence Interval -0.61 |
Secondary
Chronic Obstructive Pulmonary Disease (COPD) Symptom Night-time Awakenings Score
Mean change in COPD symptom night-time awakening score from baseline to the average of the treatment period. 0=(no symptom)-4=(no sleep)
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Chronic Obstructive Pulmonary Disease (COPD) Symptom Night-time Awakenings Score | -0.23 Score on a scale | 95% Confidence Interval -0.47 |
| Placebo | Chronic Obstructive Pulmonary Disease (COPD) Symptom Night-time Awakenings Score | -0.24 Score on a scale | 95% Confidence Interval -0.49 |
Secondary
Chronic Obstructive Pulmonary Disease (COPD) Symptom Sputum Score
Mean change in COPD symptom sputum score from baseline to the average of the treatment period. 0= (none) - 4= (severe).
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Chronic Obstructive Pulmonary Disease (COPD) Symptom Sputum Score | -0.32 Score on a scale | 95% Confidence Interval -0.52 |
| Placebo | Chronic Obstructive Pulmonary Disease (COPD) Symptom Sputum Score | -0.38 Score on a scale | 95% Confidence Interval -0.6 |
Secondary
Clinical Chronic Obstructive Pulmonary Disease (COPD) The Clinical COPD Questionnaire (CCQ)
Change in total CCQ score from baseline to last measurement on treatment. scored on a scale of 0 - 6. 0 =(low symptoms)-6 =(high symptoms)
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Clinical Chronic Obstructive Pulmonary Disease (COPD) The Clinical COPD Questionnaire (CCQ) | -0.38 Scores on a scale | 95% Confidence Interval -0.69 |
| Placebo | Clinical Chronic Obstructive Pulmonary Disease (COPD) The Clinical COPD Questionnaire (CCQ) | -0.34 Scores on a scale | 95% Confidence Interval -0.68 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1)
Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to end of treatment
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Forced Expiratory Volume in 1 Second (FEV1) | -4.77 percentage change | 95% Confidence Interval -15.94 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) | 6.16 percentage change | 95% Confidence Interval -5.66 |
Secondary
Peak Expiratory Flow (PEF) Evening
Mean change in Peak Expiratory Flow (PEF) evening from baseline to the average of the treatment period
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Peak Expiratory Flow (PEF) Evening | 1.31 L/min | 95% Confidence Interval -13.03 |
| Placebo | Peak Expiratory Flow (PEF) Evening | 1.46 L/min | 95% Confidence Interval -14.27 |
Secondary
Peak Expiratory Flow (PEF) Morning
Mean change in Peak Expiratory Flow (PEF) morning from baseline to the average of the treatment period
Time frame: Before and after 1 month treatment
Population: Efficacy analyses were performed on the full-analysis set, comprised of 51 patients: 25 in the AZD1981 group and 26 in the placebo group. However, not all patients will have valid, non-missing values for a given outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1981 | Peak Expiratory Flow (PEF) Morning | 2.57 L/min | 95% Confidence Interval -9.55 |
| Placebo | Peak Expiratory Flow (PEF) Morning | -4.14 L/min | 95% Confidence Interval -16.96 |