A 4 Week Study to Investigate the Safety and Tolerability of AZD5069 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of this study is the evaluate the safety and tolerability of AZD5069 in patients with Chronic Obstructive Pulmonary Disease

Official Title
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A 4 Week, Double Blind, Placebo Controlled, Randomised, Parallel Group, Multicentre, Phase IIa Study to Investigate the Safety and Tolerability of AZD5069 as Oral Capsules in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Conditions
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Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD), Laymen Terminology Chronic Bronchitis and Emphysema

Intervention / Treatment
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* Drug: Placebo
* Drug: AZD5069 50mg
* Drug: AZD5069 80mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of COPD with symptoms for more than one year before screening Body mass index of 18-30 kg/m2 and weight of 50-100kg Current or ex-smokers with a smoking history of at least 10 pack years (1 pack year = tobacco consumption corresponding to 20 cigarettes smoked per day for one year) at screening FEV1 of 30% or above and less than 80% of the predicted normal value post-bronchodilator at screening FEV1/FVC less than 70% post-bronchodilator at screening Exclusion Criteria: Any clinically significant disease or disorder Exacerbation of COPD which was not resolved within 30 days of first dosing Patients who have received live or live-attenuated vaccine in the 2 weeks prior to first dosing Asthma and any current respiratory tract disorder other than COPD which is considered to be clinically significant Disease history suggesting reduced or abnormal immune function other than that related to COPD

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo dose | Drug: Placebo<br>* Oral dose bid<br>|
| Experimental: 2<br>Treatment arm AZD5069 50mg | Drug: AZD5069 50mg<br>* Oral dose bid<br>|
| Experimental: 3<br>Treatment arm AZD5069 80mg | Drug: AZD5069 80mg<br>* Oral dose bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients Who Experienced at Least One Adverse Events(s) | Adverse event (AE) data, both serious and non-serious. An AE is the development of an undesirable medical condition (eg, nausea, chest pain, tachycardia, laboratory findings) or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. | From start of treatment (Day 0) up to 28 days (End of Treatment) | 
| Number of Participants With Abnormal Physical Examination Findings | Physical examination includes assessment of general appearance, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, musculo-skeletal (including spine and extremities), cardiovascular, lungs and abdomen. The findings were deemed to be normal/abnormal based on the clinical judgment of the investigator. | Last Observation on Treatment (up to Day 28) | 
| Number of Participants With Abnormal Electrocardiogram (ECG) | ECGs were recorded in the supine position after the patient has rested for 10 minutes. Heart rate, QRS duration, PR, RR and QT intervals were recorded. Overall evaluation of the ECG is classified as normal, abnormal or borderline. Only participants with ECG at baseline classified as normal are reported (ie, only changes from normal to abnormal). | Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) | 
| Change From Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample) | The change in circulating leucocyte counts (including neutrophils) is calculated as the End of Treatment value minus the Baseline value. | Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) | 
| Change From Baseline to End of Treatment for Body Temperature | The change in body temperature (oral) is calculated as the End of Treatment value minus the Baseline value. | Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) | 
| Change From Baseline to End of Treatment for Systolic Blood Preassure (Vital Signs) | The change in systolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value. | Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) | 
| Change From Baseline to End of Treatment for Diastolic Blood Pressure (Vital Signs) | The change in diastolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value. | Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) | 
| Change From Baseline to End of Treatment for Pulse Rate (Vital Signs) | The change in pulse rate (Vital Sign) is calculated as the End of Treatment value minus the Baseline value. | Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) | 
| Change From Baseline to End of Treatment for FEV1 Pre-bronchodilator (Lung Function Test) | The change in FEV1 Pre-bronchodilator is calculated as the End of Treatment value minus the Baseline value. | Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) | 
| Change From Baseline to End of Treatment for FEV1 Post-bronchodilator (Lung Function Test) | The change in FEV1 Post-bronchodilator is calculated as the End of Treatment value minus the Baseline value. | Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) | 
| Number of Participants Who Developed High Transaminase Values (Clinical Chemistry) | High Transaminase Values are defined as a measurment of ALT (alanine aminotransferase) or AST (aspartate aminotransferase) greater than or equal to 3 times the upper limit of normal (ALT ULN = 36 IU/L, AST ULN = 33 IU/L). | Up to Follow-up Visit (3 to 18 days after End of Treatment [Day 28]) | 
| Change From Baseline to End of Treatment for Total Protein (Urinalysis) | The change in total protein in urine is calculated as the End of Treatment value minus the Baseline value. | Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of AZD5069 After 1 Hour of Dosing | At this visit, approximately 1 hour after dosing (at the clinic), a blood sample was collected for determination of drug concentration in plasma. | End of Treatment (Day 28), 1 hour after dosing | 
| Area Under the Plasma Concentration Curve of AZD5069 | The area under the plasma concentration curve is estimated from time 0 (dosing) to 24 hours after dosing. | End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing | 
| Maximum Plasma Concentration for AZD5069 | The maximum plasma concentration (Cmax) is the highest level of drug in plasma. | End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing | 
| Time to Maximum Plasma Concentration for AZD5069 | Time (in relation to dosing) at which the maximum plasma concentration is observed. | End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing | 
| Maximum Reduction of Circulating Neutrophils in Blood, From Baseline | The change in circulating neutrophils in blood is calculated as the visit value minus the Baseline value. Only participants with reduction are considered. | Baseline (last non-missing assessment prior to first dose of study medication), weeks 1, 2 and 3, and End of Treatment (Day 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, Neutrophil, Respiratory Disease