Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD
Brief summary
The primary aim of this study is to investigate the effects of AZD1236 compared with placebo (inactive substance) in COPD patients by analysing biomarkers for inflammation and tissue degradation in blood, urine and sputum.
Interventions
DRUGAZD1236
oral tablet, 75 mg, twice daily during 6 weeks
DRUGPlacebo
Dosing to match AZD1236
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of COPD for 1 month * Men or postmenopausal women * Spirometry values indicating symptomatic patients * Smoking history equivalent to using 20 cigarettes a day for 10 years.
Exclusion criteria
* Any current respiratory tract disorders other than COPD * Requirement for regular oxygen therapy * Acute worsening of COPD (exacerbation) 1,5 month prior to study drug administration * Use of oral or parenteral glucocorticosteroids within 30 days and use of inhaled steroids 14 days prior to the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of TNF Alpha at Week 6 to Baseline | Baseline and Week 6 | Ratio reflects Sputum Tumor Necrosis Factor alpha (TNF alpha) at week 6 value divide by baseline value. Baseline is geometric mean of Visit 2 (last value during run-in) and Visit 3 (Randomization). |
| Ratio of Sputum Total Cells at Week 6 to Baseline | Baseline and Week 6 | Ratio reflects Sputum Total Cells at week 6 value divide by baseline value. Baseline is geometric mean of Visit 2 (last value during run-in) and Visit 3 (Randomization). |
| Ratio of Total Urine Desmosine at Week 6 to Baseline | Baseline and Week 6 | Ratio reflects Total Urine Desmosine at week 6 value divide by baseline value. Baseline is visit 3(Randomization) value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Vital Capacity (VC) at Week 6 | Baseline and Week 6 | Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value. |
| Change From Baseline in Inspiratory Capacity (IC) at Week 6 | Baseline and Week 6 | Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value. |
| Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Week 6 | Baseline and Week 6 | Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value. |
| Change From Baseline in Peak Expiratory Flow (PEF) Morning at Average of Last 4 Week Treatment | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. |
| Change From Baseline in Peak Expiratory Flow (PEF) Evening at Average of Last 4 Week Treatment | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. |
| Incidence of Adverse Events | all study visits | Number of patients who had an AE |
| Change From Baseline in COPD Symptoms, Breathlessness at Average of Last 4 Week Treatment | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Severe). |
| Change From Baseline in COPD Symptoms, Chest Tightness at Average of Last 4 Week Treatment | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Severe). |
| Change From Baseline in COPD Symptoms, Cough Score at Average of Last 4 Week Treatment | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Almost Constant). |
| Change From Baseline in COPD Symptoms, Night Time Awakenings at Average of Last 4 Week Treatment | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Almost Constant). |
| Change From Baseline in Clinical COPD Questionnaire(CCQ) Total | Baseline and Week 6 | Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value. The total scores vary between 0 (never/not limited at all) to 6 (almost all the time/totally limited) |
| Change From Baseline in Forced Expiratory Volume (FEV1) at Week 6 | Baseline and Week 6 | Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value. |
| Change From Baseline in Forced Vital Capacity (FVC) at Week 6 | Baseline and Week 6 | Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value. |
Countries
Denmark, Finland, Netherlands, Norway
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZD1236 AZD1236 75mg oral tablet twice daily(bid) | 26 |
| Placebo Placebo to AZD1236 twice daily(bid) | 29 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 |
Baseline characteristics
| Characteristic | AZD1236 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.9 Year | 65.7 Year | 64.1 Year |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 19 Participants | 20 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 26 | 10 / 29 |
| serious Total, serious adverse events | 4 / 26 | 0 / 29 |
Outcome results
Primary
Ratio of Sputum Total Cells at Week 6 to Baseline
Ratio reflects Sputum Total Cells at week 6 value divide by baseline value. Baseline is geometric mean of Visit 2 (last value during run-in) and Visit 3 (Randomization).
Time frame: Baseline and Week 6
Population: Full analysis set excluded participants without baseline or post-baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Ratio of Sputum Total Cells at Week 6 to Baseline | 1.07 ratio | Full Range 0.209 |
| Placebo | Ratio of Sputum Total Cells at Week 6 to Baseline | 0.876 ratio | Full Range 0.002 |
Primary
Ratio of TNF Alpha at Week 6 to Baseline
Ratio reflects Sputum Tumor Necrosis Factor alpha (TNF alpha) at week 6 value divide by baseline value. Baseline is geometric mean of Visit 2 (last value during run-in) and Visit 3 (Randomization).
Time frame: Baseline and Week 6
Population: Full analysis set excluded participants without baseline or post-baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Ratio of TNF Alpha at Week 6 to Baseline | 1.37 ratio | Full Range 0.532 |
| Placebo | Ratio of TNF Alpha at Week 6 to Baseline | 1.21 ratio | Full Range 0.27 |
Primary
Ratio of Total Urine Desmosine at Week 6 to Baseline
Ratio reflects Total Urine Desmosine at week 6 value divide by baseline value. Baseline is visit 3(Randomization) value.
Time frame: Baseline and Week 6
Population: Full analysis set excluded participants without baseline or post-baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Ratio of Total Urine Desmosine at Week 6 to Baseline | 0.946 ratio | Full Range 0.24 |
| Placebo | Ratio of Total Urine Desmosine at Week 6 to Baseline | 1.27 ratio | Full Range 0.387 |
Secondary
Change From Baseline in Clinical COPD Questionnaire(CCQ) Total
Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value. The total scores vary between 0 (never/not limited at all) to 6 (almost all the time/totally limited)
Time frame: Baseline and Week 6
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in Clinical COPD Questionnaire(CCQ) Total | 0.011 Score on scale | Full Range -0.8 |
| Placebo | Change From Baseline in Clinical COPD Questionnaire(CCQ) Total | -0.241 Score on scale | Full Range -1.74 |
Secondary
Change From Baseline in COPD Symptoms, Breathlessness at Average of Last 4 Week Treatment
Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Severe).
Time frame: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in COPD Symptoms, Breathlessness at Average of Last 4 Week Treatment | -0.191 Score on scale | Full Range -1.51 |
| Placebo | Change From Baseline in COPD Symptoms, Breathlessness at Average of Last 4 Week Treatment | -0.338 Score on scale | Full Range -1.74 |
Secondary
Change From Baseline in COPD Symptoms, Chest Tightness at Average of Last 4 Week Treatment
Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Severe).
Time frame: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in COPD Symptoms, Chest Tightness at Average of Last 4 Week Treatment | -0.149 Score on scale | Full Range -1.11 |
| Placebo | Change From Baseline in COPD Symptoms, Chest Tightness at Average of Last 4 Week Treatment | -0.156 Score on scale | Full Range -1.74 |
Secondary
Change From Baseline in COPD Symptoms, Cough Score at Average of Last 4 Week Treatment
Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Almost Constant).
Time frame: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in COPD Symptoms, Cough Score at Average of Last 4 Week Treatment | -0.114 Score on scale | Full Range -1.81 |
| Placebo | Change From Baseline in COPD Symptoms, Cough Score at Average of Last 4 Week Treatment | -0.324 Score on scale | Full Range -1.94 |
Secondary
Change From Baseline in COPD Symptoms, Night Time Awakenings at Average of Last 4 Week Treatment
Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in. Score vary between 0 (None) to 4 (Almost Constant).
Time frame: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in COPD Symptoms, Night Time Awakenings at Average of Last 4 Week Treatment | 0.072 Score on scale | Full Range -0.556 |
| Placebo | Change From Baseline in COPD Symptoms, Night Time Awakenings at Average of Last 4 Week Treatment | -0.150 Score on scale | Full Range -2.22 |
Secondary
Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Week 6
Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time frame: Baseline and Week 6
Population: Full analysis set completed at week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Week 6 | -0.007 L/s | Full Range -0.41 |
| Placebo | Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Week 6 | -0.067 L/s | Full Range -0.78 |
Secondary
Change From Baseline in Forced Expiratory Volume (FEV1) at Week 6
Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time frame: Baseline and Week 6
Population: Full analysis set completed at week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in Forced Expiratory Volume (FEV1) at Week 6 | -0.025 L | Full Range -0.51 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Week 6 | -0.063 L | Full Range -0.67 |
Secondary
Change From Baseline in Forced Vital Capacity (FVC) at Week 6
Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time frame: Baseline and Week 6
Population: Full analysis set completed at week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in Forced Vital Capacity (FVC) at Week 6 | -0.103 L | Full Range -0.96 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 6 | -0.104 L | Full Range -0.9 |
Secondary
Change From Baseline in Inspiratory Capacity (IC) at Week 6
Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time frame: Baseline and Week 6
Population: Full analysis set completed at week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in Inspiratory Capacity (IC) at Week 6 | -0.082 L | Full Range -0.7 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC) at Week 6 | -0.173 L | Full Range -2.19 |
Secondary
Change From Baseline in Peak Expiratory Flow (PEF) Evening at Average of Last 4 Week Treatment
Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in.
Time frame: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in Peak Expiratory Flow (PEF) Evening at Average of Last 4 Week Treatment | -13.6 L/min | Full Range -80.3 |
| Placebo | Change From Baseline in Peak Expiratory Flow (PEF) Evening at Average of Last 4 Week Treatment | -13.5 L/min | Full Range -102 |
Secondary
Change From Baseline in Peak Expiratory Flow (PEF) Morning at Average of Last 4 Week Treatment
Change from baseline reflects the average of last 4 week on treatment (Week 1, Week 2, Week 4 and Week 6) minus the baseline value. Baseline is the mean of the last 10 days of data during run-in.
Time frame: Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6)
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in Peak Expiratory Flow (PEF) Morning at Average of Last 4 Week Treatment | -9.81 L/min | Full Range -61.2 |
| Placebo | Change From Baseline in Peak Expiratory Flow (PEF) Morning at Average of Last 4 Week Treatment | -7.73 L/min | Full Range -73.2 |
Secondary
Change From Baseline in Vital Capacity (VC) at Week 6
Change from baseline reflects the Week 6 value minus the baseline value. Baseline is visit 3(randomization) value.
Time frame: Baseline and Week 6
Population: Full analysis set completed at week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1236 | Change From Baseline in Vital Capacity (VC) at Week 6 | 0.098 L | Full Range -0.68 |
| Placebo | Change From Baseline in Vital Capacity (VC) at Week 6 | -0.110 L | Full Range -0.84 |
Secondary
Incidence of Adverse Events
Number of patients who had an AE
Time frame: all study visits
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD1236 | Incidence of Adverse Events | 15 Participants |
| Placebo | Incidence of Adverse Events | 15 Participants |