A Phase IIa Study Assessing the Effects of AZD1236 on Biomarkers in Chronic Obstructive Pulmonary Disease (COPD) Patients

Study Overview
=================
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.

Official Title
-----------------
A Double-blind, Randomised, Placebo-controlled, Parallel Group Multi-centre Phase IIa Study to Assess the Effects on Biomarkers in Induced Sputum, Bood and Uine of AZD1236 Administered as Oral Tablet in Moderate to Severe COPD Patients During a 6 Week Period.

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: AZD1236
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD1236<br>oral tablet, 75 mg, twice daily during 6 weeks | Drug: AZD1236<br>* oral tablet, 75 mg, twice daily during 6 weeks<br>|
| Placebo Comparator: Placebo<br>Dosing to match AZD1236 | Drug: Placebo<br>* Dosing to match AZD1236<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline and Week 6 | 
| 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). | Baseline and Week 6 | 
| 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. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | Number of patients who had an AE | all study visits | 
| 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. | Baseline and Week 6 | 
| 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. | Baseline and Week 6 | 
| 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. | Baseline and Week 6 | 
| 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. | Baseline and Week 6 | 
| 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. | Baseline and Week 6 | 
| 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. | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | 
| 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. | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | 
| 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) | Baseline and Week 6 | 
| 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). | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | 
| 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). | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | 
| 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). | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | 
| 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). | Baseline and last 4 week on treatment(Week 1, Week 2, Week 4 and Week 6) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD