Chronic Obstructive Pulmonary Disease COPD
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD patients, Exacerbations, ICS, LABA
Brief summary
The purpose of this study is to determine whether AZD7624 can reduce acute Chronic Obstructive Pulmonary Disease (COPD) exacerbations in patients on COPD maintenance therapy with a history of frequent acute exacerbations.
Interventions
DRUGAZD7624 1.0 mg
Inhaled AZD7624 solution, 11 mg/mL
DRUGPlacebo
Inhaled placebo solution
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated written informed consent prior to any study specific procedures. * Male and females aged 40-85 years. Females must have a negative pregnancy test at Visit 1, must not be lactating and must be of non-childbearing potential. Males must be surgically sterile or agree to use an acceptable method of contraception for the duration of the study and for 3 months after the last dose of investigational product to prevent pregnancy in a partner. * A weight of ≥50 kg. * Diagnosis of COPD for more than 1 year at Visit 1, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014 guidelines. * COPD maintenance treatment with at least ICS/LABA for at least 2 months prior to enrolment to be continued unchanged during the study. * A post-bronchodilator FEV1/FVC \<0.70 and a post-bronchodilator FEV1 ≤70% of the predicted normal value. Documented history of 2 or more moderate to severe COPD exacerbations within 12 months of randomisation, but not within the last 6 weeks before randomisation. * Current or ex-smokers with a smoking history of at least 10 pack-years.
Exclusion criteria
* Involvement in the planning and conduct of the study. * Previous randomisation in the present study. * Participation in another clinical study with any investigational medicinal product within 3 months of randomisation. Previously intake of any p38 inhibitor. * Participation in, or scheduled for an intensive COPD rehabilitation programme at any time during the study. * Planned in-patient surgery or hospitalisation during the study. * Significant disease or disorder other than COPD which, may either put the patient at risk because of participation in the study, or influence the results of the study, or the patient's ability to participate in the study. Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines (GINA 2013) or other accepted guidelines. * A clinically relevant abnormal findings in clinical chemistry, haematology and urinalysis. * Plasma myoglobin and CK above the upper reference range of the analysing laboratory at randomization. * A clinically relevant abnormal findings in physical examination, pulse or blood pressure. * A positive result on screening for serum hepatitis B hepatitis C and Human Immunodeficiency Virus (HIV). * History or family history of muscle diseases. Abnormal vital signs, defined as Systolic Blood Pressure (SBP) above 140 mmHg if \<60 years of age and above 150 mmHg if ≥60 years of age; Diastolic Blood Pressure (DBP) above 90 mmHg; Pulse \<50 or \>100 bpm. * Prolonged QTcF \>450 ms or family history of long QT syndrome or sudden death at young age. PR(PQ) interval of clinical significance, PR(PQ) \> 250 ms. * Intermittent AV block of 2nd and 3rd degree or AV dissociation. * Patients with a QRS duration \>120 ms. * Patients with persistent, and/or recurrent symptomatic tachyarrhythmias, as well as patients with an implantable cardioverter-defibrillator (ICD) or a permanent pacemaker. * Patients with recent Cardiovascular (CV) events or unstable CV disease or a myocardial infarction or stroke within 6 months of screening. History of hospitalization within 12 months caused by heart failure or a diagnosis of heart failure higher than New York Heart Association (NYHA) class II. * History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to AZD7624. * Any exacerbation or respiratory infection within 6 weeks of randomization. * Plasma donation within one month of Visit 1, or any blood donation/blood loss \>500 mL during the 3 months prior to Visit 1. * History of, or current alcohol or drug abuse. * Treatment with any GCS (apart from prescribed steroids at run-in) within 6 weeks of Visit 3 regardless of indication. * Treatment with strong CYP3A inhibitors within 4 weeks prior to randomisation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | — |
| Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Event Rate = No. of Events\*365.25 / (Follow-up date - Date of randomization + 1). |
| Time to First Moderate or Severe Exacerbation | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | — |
| Annual Exacerbation Rate of Moderate and Severe Exacerbations | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Exacerbation Rate = No. of Exacerbations\*365.25 / (Follow-up date - Date of randomization + 1). |
| Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | — |
| Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Exacerbation Rate = No. of Exacerbations\*365.25 / (Follow-up date - Date of randomization + 1). |
| Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | — |
| Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Event Rate = No. of Events\*365.25 / (Follow-up date - Date of randomization + 1). |
| Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | The EXACT for Respiratory Symptoms (E-RS) scale is a derivative instrument comprising a subset of 11 of the EXACT items to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity. |
| Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C]) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | The SGRQ-C is a modified version of the St. George's Respiratory Questionnaire, which has been developed to measure the impact of respiratory disease on health status. The SGRQ-C includes 14 questions in 3 domains: symptoms; activity; and impacts. Scores range from 0 to 100 with higher scores indicating benefit. Change in total score from pre study-treatment baseline to Week 12 end of treatment visit are reported. |
| Dyspnea (Transitional Dyspnea Index (TDI) Score) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | The Baseline/Transitional Dyspnea Index (BDI/TDI) provides a multidimensional measure of dyspnea in relation to activities of daily living. The BDI provides a measure of dyspnoea at a single state, the baseline, and the TDI evaluates changes in dyspnoea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference. |
| Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | — |
| Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | — |
| Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | — |
| Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary) | Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days) | For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Exacerbation Rate = No. of Exacerbations\*365.25 / (Follow-up date - Date of randomization + 1). |
Countries
Argentina, Chile, Netherlands, Peru, South Africa, United States
Participant flow
Recruitment details
This was a multi-centre study conducted at 39 study centres in 6 countries: Argentina (37.7% of the patients); United States (34.4%) Peru (9%) Chile (6.6%) The Netherlands (6.1%) and South Africa (6.1%) A seasonal recruitment strategy was undertaken where patients were recruited in the fall and winter months of the geographic locality.
Pre-assignment details
327 patients signed informed consent, of which 213 patients were randomised. The majority of the 114 not randomised were screening failures
Participants by arm
| Arm | Count |
|---|---|
| AZD7624 Active treatment 2 x 0.5mg inhalation qd | 107 |
| Placebo Matching placebo comparator | 105 |
| Total | 212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 3 |
| Overall Study | Completion status not recorded | 1 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Illness in family member | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 7 |
| Overall Study | Withdrawn due to physician decision | 1 | 0 |
Baseline characteristics
| Characteristic | AZD7624 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 58 Participants | 51 Participants | 109 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 54 Participants | 103 Participants |
| Age, Continuous | 65.4 Years STANDARD_DEVIATION 8.73 | 64.2 Years STANDARD_DEVIATION 8.67 | 64.8 Years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 66 Participants | 65 Participants | 131 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 40 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 12 Participants | 11 Participants | 23 Participants |
| Race/Ethnicity, Customized White | 85 Participants | 88 Participants | 173 Participants |
| Sex: Female, Male Female | 40 Participants | 36 Participants | 76 Participants |
| Sex: Female, Male Male | 67 Participants | 69 Participants | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 71 / 108 | 48 / 105 |
| serious Total, serious adverse events | 11 / 108 | 11 / 105 |
Outcome results
Primary
Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD7624 | Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms | NA days |
| Placebo | Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms | 118.0 days |
Comparison: H0: Hazard Ratio (AZD7624/placebo) equals 1 vs. H1: Hazard Ratio does not equal 1.p-value: 0.237195% CI: [0.81, 2.4]Regression, Cox
Secondary
Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause)
For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Event Rate = No. of Events\*365.25 / (Follow-up date - Date of randomization + 1).
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause) | 2.17 Events / year | Standard Error 0.8 |
| Placebo | Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause) | 1.55 Events / year | Standard Error 0.6 |
p-value: 0.15795% CI: [0.88, 2.21]regression, negative binomial
Secondary
Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo)
For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Event Rate = No. of Events\*365.25 / (Follow-up date - Date of randomization + 1).
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo) | 2.16 Events / year | Standard Error 0.8 |
| Placebo | Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo) | 1.62 Events / year | Standard Error 0.63 |
p-value: 0.24995% CI: [0.82, 2.16]regression, negative binomial
Secondary
Annual Exacerbation Rate of Moderate and Severe Exacerbations
For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Exacerbation Rate = No. of Exacerbations\*365.25 / (Follow-up date - Date of randomization + 1).
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Annual Exacerbation Rate of Moderate and Severe Exacerbations | 2.12 Exacerbations / year | Standard Error 0.78 |
| Placebo | Annual Exacerbation Rate of Moderate and Severe Exacerbations | 1.42 Exacerbations / year | Standard Error 0.56 |
p-value: 0.12995% CI: [0.89, 2.52]regression, negative binomial
Secondary
Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)
For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Exacerbation Rate = No. of Exacerbations\*365.25 / (Follow-up date - Date of randomization + 1).
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled) | 1.23 Exacerbations / year | Standard Error 0.39 |
| Placebo | Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled) | 1.09 Exacerbations / year | Standard Error 0.37 |
p-value: 0.75195% CI: [0.55, 2.29]regression, negative binomial
Secondary
Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary)
For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Exacerbation Rate = No. of Exacerbations\*365.25 / (Follow-up date - Date of randomization + 1).
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary) | 1.96 Exacerbations / year | Standard Error 0.54 |
| Placebo | Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary) | 2.33 Exacerbations / year | Standard Error 0.64 |
p-value: 0.4495% CI: [0.55, 1.3]regression, negative binomial
Secondary
Dyspnea (Transitional Dyspnea Index (TDI) Score)
The Baseline/Transitional Dyspnea Index (BDI/TDI) provides a multidimensional measure of dyspnea in relation to activities of daily living. The BDI provides a measure of dyspnoea at a single state, the baseline, and the TDI evaluates changes in dyspnoea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference.
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. Only patients with post-baseline TDI scores were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Dyspnea (Transitional Dyspnea Index (TDI) Score) | 0.41 score on a scale | Standard Error 0.15 |
| Placebo | Dyspnea (Transitional Dyspnea Index (TDI) Score) | 0.54 score on a scale | Standard Error 0.16 |
p-value: 0.269495% CI: [-0.34, 0.1]Mixed Models Analysis
Secondary
Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C])
The SGRQ-C is a modified version of the St. George's Respiratory Questionnaire, which has been developed to measure the impact of respiratory disease on health status. The SGRQ-C includes 14 questions in 3 domains: symptoms; activity; and impacts. Scores range from 0 to 100 with higher scores indicating benefit. Change in total score from pre study-treatment baseline to Week 12 end of treatment visit are reported.
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C]) | -4.03 scores on a scale | Standard Deviation 19.574 |
| Placebo | Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C]) | -5.11 scores on a scale | Standard Deviation 17.809 |
p-value: 0.635295% CI: [-2.62, 4.29]Mixed Models Analysis
Secondary
Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio | 0.0077 L/L | Standard Deviation 0.05269 |
| Placebo | Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio | -0.0072 L/L | Standard Deviation 0.05255 |
p-value: 0.196595% CI: [0, 0.02]Mixed Models Analysis
Secondary
Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1) | -0.003 Litres | Standard Deviation 0.2555 |
| Placebo | Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1) | -0.028 Litres | Standard Deviation 0.2317 |
p-value: 0.514495% CI: [-0.03, 0.07]Mixed Models Analysis
Secondary
Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC)
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC) | -0.045 Litres | Standard Deviation 0.4017 |
| Placebo | Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC) | -0.018 Litres | Standard Deviation 0.389 |
p-value: 0.541695% CI: [-0.1, 0.05]Mixed Models Analysis
Secondary
Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary)
The EXACT for Respiratory Symptoms (E-RS) scale is a derivative instrument comprising a subset of 11 of the EXACT items to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD7624 | Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary) | -0.21 scores on a scale | Standard Error 0.88 |
| Placebo | Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary) | 0.17 scores on a scale | Standard Error 0.91 |
p-value: 0.547495% CI: [-1.6, 0.85]Mixed Models Analysis
Secondary
Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause)
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD7624 | Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause) | NA days |
| Placebo | Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause) | 118.0 days |
p-value: 0.126195% CI: [0.89, 2.5]Regression, Cox
Secondary
Time to First Moderate or Severe Exacerbation
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD7624 | Time to First Moderate or Severe Exacerbation | NA days |
| Placebo | Time to First Moderate or Severe Exacerbation | NA days |
p-value: 0.152995% CI: [0.85, 2.76]Regression, Cox
Secondary
Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD7624 | Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled) | NA days |
| Placebo | Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled) | NA days |
p-value: 0.854395% CI: [0.43, 2.01]Regression, Cox
Secondary
Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary)
Time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
Population: The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD7624 | Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary) | NA days |
| Placebo | Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary) | NA days |
p-value: 0.538195% CI: [0.54, 1.38]Regression, Cox