A Two Week Study to Assess the Tolerability of AZD9668 in Chronic Obstructive Pulmonary Disease (COPD) Patients

Study Overview
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Brief Summary
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The purpose of this study is to assess the tolerability (effect of drug on body) and pharmacokinetics (effect of body on drug) of AZD9668 in patients with mild to moderate COPD

Official Title
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A 2-week, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Tolerability and Pharmacokinetics of Orally Administered AZD9668 in Patients With COPD

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: AZD9668
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild to moderate COPD Smokers or ex-smokers post-menopausal females Exclusion Criteria: Past history or current evidence of clinically significant heart disease Lung disease other than COPD Treatment with systemic steroids within 8 weeks of study visit 2 Treatment with antibiotics within 4 weeks of study visit 1 or study visit 2

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Active Treatment | Drug: AZD9668<br>* 30mg oral tablets twice daily (bid) for 14 days<br>|
| Placebo Comparator: 2<br>Placebo Treatment | Drug: Placebo<br>* Matched placebo to 30mg oral tablet twice daily (bid) for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alanine Aminotransferase (ALT) | ALT level greater than 3 times the upper limit of normal | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| Aspartate Aminotransferase (AST) | AST level greater than 3 times the upper limit of normal | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| Creatine Kinase (CK) | Change from baseline to Day 14 | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| Total Bilirubin | Change from baseline to Day 14 | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| Creatinine | Creatinine level greater than the upper limit of normal | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| Haemoglobin (Hb) | Change from baseline to Day 14 | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| Reticulocytes | Change from baseline to Day 14 | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| Leucocytes | Change from baseline to Day 14 | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| QTcF (QT Interval Corrected for Heart Rate by Fridericia's Method) | QTcF interval greater than 450 ms | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| QTcF | QTcF change from baseline greater than 60 ms | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| FEV1 (Forced Expiratory Volume in the First Second) | Change from baseline to Day 14 | Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose) | 
| Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC(0-12)) | AUC(0-12) following 14 days' dosing | Pre-dose on day -1 to day 15 (end of dosing) | 
| Observed Peak or Maximum Plasma Concentration Following Drug Administration (Cmax) | Cmax following 14 days' dosing | Pre-dose on day -1 to day 15 (end of dosing) | 
| Time to Reach Observed Peak or Maximum Concentration Following Oral Drug Administration (Tmax) | tmax following 14 days' dosing | Pre-dose on day -1 to day 15 (end of dosing) | 
| Terminal Half-life of Drug in Plasma (t1/2) | t1/2 following 14 days' dosing | Pre-dose on day -1 to day 15 (end of dosing) | 
| Renal Clearance of Drug From Plasma (CLR) | CLR following 14 days' dosing | Pre-dose on day -1 to day 15 (end of dosing) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum Absolute Neutrophil Count | Change from baseline to Day 14 in absolute neutrophil count | Pre-dose day -1 to post-dose on day 14 | 
| Sputum Differential Neutrophil Count | Change from baseline to Day 14 in percentage neutrophil count | Pre-dose day -1 to post-dose on day 14 | 
| AZD9668 Sputum Concentrations |  | Pre-dose day -1 to post-dose on day 14 | 
| Quantitative Sputum Bacteriology | Number of patients with an increase in bacteriological count from Day -1 to Day 15 | Pre-dose day -1 to post-dose on day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung, Chronic, obstructive, pulmonary, respiratory disease, tolerability, placebo-controlled, pharmacokinetics, COPD