The Study Will Evaluate the Effect of AZD9164 in Patients With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Chronic Obstructive Pulmonary Disease (COPD) is a chronic respiratory condition with deteriorating lung function over the years. Patients with COPD experience symptoms of shortness of breath, cough and sputum production. This study is to assess the treatment effects after inhalation of three different single doses of AZD9164 (100, 400 and 1200 mcg) and one single dose of tiotropium (18 mcg). One dose of placebo will be given as comparator. 25 patients are to participate in the study and all will be recruited in Sweden. Each patient will visit the study doctor 9 times during the study, whereof 5 visits will be overnight visits. All examinations, treatment and the follow-up is free of charge.

Official Title
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A Double-blind, Double-dummy, Placebo-controlled, Randomised, Multi-centre, 5-way Cross-over, Single-dose Study to Investigate the Local and Systemic Effects of Inhaled AZD9164 Compared to Tiotropium in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: AZD9164
* Drug: Tiotropium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical diagnosis of COPD FEV1 40 - 80% of the predicted normal value (post-bronchodilator) and post- bronchodilator FEV1/FVC < 70% Exclusion Criteria: Any clinically relevant abnormal findings at screening examinations Any clinically significant disease or disorder

Ages Eligible for Study
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Minimum Age: 40 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD9164 100 mcg First, then Placebo for Spririva<br>1 x AZD9164 solution for inhalation through nebulisation 100 mcg (lung deposited dose) + 1 x placebo for Spiriva dry powder for inhalation | Drug: AZD9164<br>* Solution for inhalation through nebulization, single dose<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: AZD9164 400 mcg First, then Placebo for Spiriva<br>1 x AZD9164 solution for inhalation through nebulisation 400 mcg (lung deposited dose) + 1 x placebo for Spiriva dry powder for inhalation | Drug: AZD9164<br>* Solution for inhalation through nebulization, single dose<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: AZD9164 1200 mcg First, then Placebo for Spiriva<br>1 x AZD9164 solution for inhalation through nebulisation 1200 mcg (lung deposited dose) + 1 x placebo for Spiriva dry powder for inhalation | Drug: AZD9164<br>* Solution for inhalation through nebulization, single dose<br>Drug: Placebo<br>* Placebo<br>|
| Active Comparator: Spiriva 18 mcg First, then Placebo for AZD9164<br>1 x Spiriva dry powder for inhalation 18 mcg + 1 x placebo for AZD9164 (sodium chloride) | Drug: Tiotropium<br>* Dry powder for inhalation, single dose<br>* Other names: Spiriva;Drug: Placebo<br>* Placebo<br>|
| Placebo Comparator: Placebo for Spiriva First, then Placebo for AZD9164<br>1 x placebo Spiriva dry powder for inhalation + 1 x placebo for AZD9164 (sodium chloride) | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in One Second (FEV1), Peak Effect Within 0 - 24 Hours Post-dose | Maximum FEV1 value | 0, 15 min, 30 min, 60 min, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h | 
| Forced Expiratory Volume in One Second (FEV1), Average Effect Over 22 - 26 Hours Post-dose | Trough FEV1 value | 22 h, 24 h, 26 h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in One Second (FEV1), Average Effect Over 0 - 24 Hours Post Dose | Average FEV1 value | 0, 15 min, 30 min, 60 min, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 22 h, 24 h | 
| Forced Expiratory Volume in One Second (FEV1), Effect at 15 Minutes Post-dose | 15 min FEV1 value | 15 min | 
| Systolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | Average systolic blood pressure value | 0, 30 min, 2 h, 4 h | 
| Diastolic Blood Pressure, Average Effect Over 0 - 4 Hours Post-dose | Average diastolic blood pressure value | 0, 30 min, 2 h, 4 h | 
| Pulse, Average Effect Over 0 - 4 Hours Post-dose | Average pulse value | 0, 30 min, 2 h, 4 h | 
| Heart Rate, Average Effect Over 0 - 4 Hours Post-dose | Average heart rate value | 0, 30 min, 2 h, 4 h | 
| QTcF, Average Effect Over 0 - 4 Hours Post-dose | Average QTcF value | 0, 30 min, 2 h, 4 h | 
| Plasma AZD9164 Cmax | Maximum plasma concentration of AZD9164 | 0, 5 min, 15 min, 30 min, 60 min, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h | 
| Plasma AZD9164 AUC0-24 | Area under the AZD9164 plasma concentration curve | 0, 5 min, 15 min, 30 min, 60 min, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease (COPD), efficacy, safety, inhalation, long-acting muscarinic receptor antagonist (LAMA)