Effect of ADC4022 Co-Administered With Budesonide on Pulmonary Inflammation in Subjects With Moderate to Severe COPD

Study Overview
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Brief Summary
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The purpose of this study is to assess the tolerability and efficacy of inhaled theophylline (ADC4022) on markers of pulmonary inflammation (white blood cells) in induced sputum and in bronchial biopsy samples in subjects with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) when co-administered with budesonide and compared to placebo.

Official Title
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A Phase II, Randomised, Double-Blind, Placebo-Controlled Pilot Efficacy Study of ADC4022 on Markers of Pulmonary Inflammation in Subjects With Moderate to Severe COPD

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Theophylline - ADC4022
* Drug: Placebo
* Drug: Budesonide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of COPD that has been symptomatic for at least 2 years The subject has moderate to severe COPD, as defined by the American Thoracic Society and the European Respiratory Society The subject can produce an adequate sputum specimen after induction The subject has a history of ≥ 10-pack years of cigarette smoking The subject has either a ≤15% increase or ≤200 ml increase in FEV1 from pre-dose following a fixed dose of bronchodilator therapy The subject is able to provide written, informed consent to participate Exclusion Criteria: The subject has experienced a respiratory tract infection and/or an exacerbation of COPD within 30 days The subject uses systemic corticosteroids (oral or parenteral) The subject has received long term oxygen therapy within 30 days The subject has a previous history or diagnosis of asthma The subject has a chest x-ray within the past 12 months which is diagnostic of an active or clinically significant disease other than COPD The subject has a history or presence of active tuberculosis, cystic fibrosis, bronchiectasis, lung cancer or sarcoidosis or any other clinically important lung diseases The subject has had radiation or chemotherapy within the previous 12 months The subject has a history of anaphylaxis associated with medicinal products The subject is pregnant, intends to become pregnant, or is breast feeding The subject's alcohol intake is excessive. The subject participated in another study (for a marketed drug) within 3 months before the start of this study or (for an investigational drug) within 4 months before the start of this study. Other inclusion/exclusion criteria may also apply

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Theophylline - ADC4022<br>* Inhaled theophylline (ADC4022) administered twice daily for 28 days<br>* Other names: ADC4022;Drug: Budesonide<br>* Inhaled budesonide twice daily for 28 days<br>* Other names: Pulmicort;|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Inhaled matching placebo administered twice daily for 28 days<br>Drug: Budesonide<br>* Inhaled budesonide twice daily for 28 days<br>* Other names: Pulmicort;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary inflammation: Cell counts (neutrophils, macrophages, eosinophils and lymphocytes) in induced sputum samples |  | Baseline and after 4 weeks treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary inflammation: Cytokine IL-8 concentration in induced sputum |  | Baseline and after 4 weeks treatment | 
| Pulmonary inflammation: CD8+ and CD68+ from bronchial biopsy |  | Baseline and after 4 weeks treatment | 
| Tolerability to ADC4022 |  | Baseline, during 4 weeks treatment and after 1 week of follow-up | 

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