Efficacy and Safety Study of Two Dose Levels of AZD2115 in Subjects With Moderate to Severe COPD

Study Overview
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Brief Summary
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This is a phase IIa dose-ranging, randomized, double-blind, chronic-dosing (14 Days), three-period, placebo-controlled, multi-center, cross-over study to assess the efficacy and safety of two dose levels of a dual pharmacology molecule with the combined properties of a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA); (AZD2115) delivered by a metered-dose inhaler (MDI) in subjects with moderate to severe chronic obstructive pulmonary disease (COPD).

Official Title
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A Randomized, Double Blind, Chronic Dosing (14 Days), Three Period, Placebo Controlled, Cross Over, Multi Center Study to Assess Efficacy and Safety of Two Dose Levels of AZD2115 MDI in Subjects With Moderate to Severe COPD

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: AZD2115 Dose 1
* Drug: AZD 2115, Dose 2
* Drug: Placebo MDI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic Obstructive Pulmonary Disease Diagnosis: Subjects with an established clinical history of COPD for more than 1 year at Screening, according to the COPD GOLD guidelines. Current or former smokers with a history of ≥10 pack years of cigarette smoking. Post-bronchodilator FEV1/FVC ratio of <70%. Pre-bronchodilator FEV1 must be <80% predicted Women of non-child bearing potential (ie., physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or women of child bearing potential, has a negative serum pregnancy test at Screening and agrees to acceptable contraceptive methods for the duration of the study. Exclusion Criteria: Pregnancy: Women who are pregnant or lactating. Significant diseases other than COPD, ie., disease or condition which, in the opinion of the Investigator, may put the subject at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study. Primary diagnosis of asthma. Alpha-1 antitrypsin deficiency as the cause of COPD Other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or uncontrolled sleep apnea. Poorly controlled COPD (hospitalization due to poorly controlled COPD within 3 months of Screening or requiring treatment with corticosteroids or antibiotics in the 6 week interval prior to Screening or during Screening. Unstable ischemic heart disease, left ventricular failure, or documented myocardial infarction within 12 months of Randomization. Clinically significant abnormal ECG.

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD2115 Dose 1<br>AZD 2115, Dose 1 administered as two inhalations BID | Drug: AZD2115 Dose 1<br>* AZD 2115, Dose 1 administered as two inhalations BID<br>|
| Experimental: AZD 2115 Dose 2<br>AZD 2115, Dose 2 administered as two inhalations BID | Drug: AZD 2115, Dose 2<br>* AZD 2115, Dose 2 administered as two inhalations BID<br>|
| Placebo Comparator: Placebo MDI<br>Placebo MDI administered as two inhalations BID | Drug: Placebo MDI<br>* Placebo MDI administered as two inhalations BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12) relative to baseline |  | 14 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in morning pre dose trough FEV1 |  | 14 Days | 
| Peak change in FEV1 |  | 14 Days | 
| Forced vital capacity (FVC) AUC0-12 relative to baseline |  | 14 Days | 
| Peak change in FEV1 |  | Day 1 | 
| Change from baseline in 12-hour post dose trough FEV1 |  | 14 Days | 
| Time to onset of action |  | Day 1 |