A randomized, double-blind, double-dummy, two-way cross-overstudy evaluating systemic bioavailability and airway clearance ofSymbicort® Turbuhaler® 320/9µg/inhalation versus Seretide™ Diskus™50/500µg/inhalation after single inhalations in patients with ChronicObstructive Pulmonary Disease (COPD) and healthy volunteers - Airway clearance

• Conditions: This is a Clinical Pharmacology study to be conducted in one patient group with severe COPD and one group of healthy volunteers.; MedDRA version: 14.1Level: PTClassification code 10009033Term: Chronic obstructive pulmonary diseaseSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

• Registration Number: EUCTR2006-002412-10-DE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-04-18
• Last Update Posted: 7 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

COPD patients:
1. Provision of written informed consent obtained prior to study procedures
2. Outpatients, men or women = 40 years of age
3. A clinical diagnosis of COPD with symptoms for more than 1 year
4. A current or previous smoker with a smoking history equivalent to 10 or more
pack years (1 pack year = 20 cigarettes smoked per day for one year)
5. Pre-bronchodilatory FEV1 = 55% of predicted normal value
6. Pre-bronchodilatory FEV1 / VC = 70%
7. Stable symptoms without signs of infection and COPD exacerbation within 1
month prior to the study
8. Productive cough with expectoration two times or more before noon on most days
9. Ability to inhale from Turbuhaler and Diskus according to given instructions, as
judged by the investigator or study nurse
10. Body Mass Index (BMI) between 18 and 32 kg/m2

Healthy volunteers:
1. Provision of written informed consent obtained prior to study procedures
2. Men or women =18 years of age
3. Body Mass Index (BMI) between 18 and 32 kg/m2
4. Healthy, as judged by the investigator after medical history, physical examination,
vital signs, electrocardiogram (ECG), and laboratory tests
5. Pre-bronchodilatory FEV1 > 80% of predicted normal value
6. Pre-bronchodilatory FEV1 / VC > 70%
7. Ability to inhale from Turbuhaler and Diskus according to given instructions, as
judged by the investigator or study nurse
8. Non-smoker, have never been regular smoker

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

COPD patients:
1. A history of asthma and/or seasonal allergic rhinitis before 40 years of age
2. Any current respiratory tract disorder other than COPD for example bronchiectasis,
which is considered by the investigator to be clinically significant
3. Any clinically relevant abnormal findings in physical examination and vital signs,
which in the opinion of the investigator, may put the patient at risk because of
his/her participation in the study
4. Any significant disease or disorder (e.g. gastrointestinal, liver, renal, neurological,
musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical
impairment) which, in the opinion of the investigator, may either put the patient
at risk because of participation in the study, or may influence the results of the
study, or the patients ability to participate in the study
5. Patients with significant or unstable ischemic heart disease, arrhythmia,
cardiomyopathy, heart failure, uncontrolled hypertension as defined by the
investigator, or any other relevant cardiovascular disorder as judged by the
investigator
6. Use of oral or ophthalmic non-cardio selective ß-blocking agents
7. Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women
not using acceptable contraceptive measures, as judged by the investigator.
8. Known or suspected hypersensitivity to study therapy or excipients of the
investigational products.
9. Patients with a history of chronic alcohol or drug abuse or any condition associated
with poor compliance
10. Blood donation within 3 months prior to enrolment
11. Planned hospitalization during the study
12. Previously enrolled in the present study
13. Participation in another clinical study within 90 days preceding enrolment
14. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)

Healthy volunteers:
1. Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women
not using an acceptable contraceptive, as judged by the investigator. All women
must show a negative pregnancy urine test result at Visit 1.
2. Known or suspected hypersensitivity to glucocorticosteroids, ß2-adrenergic
agonists, inhaled lactose, or other excipients in study drugs
3. History and/or evidence of any significant disease or disorder (e.g. respiratory,
cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal,
endocrine, metabolic, malignant, psychiatric, major physical impairment) which,
in the opinion of the investigator, may either put the subject at risk because of
participation in the study, or may influence the results of the study, or the subject’s
ability to participate in the study. Evidence of HIV or hepatitis B or C-infection.
4. Significant illness as judged by the investigator or intake of any prescribed
medication within two weeks prior to enrolment .
5. Use of any regular medication or therapy, including over-the-counter remedies,
herbal preparations, vitamins, and mineral supplements 2 weeks prior to enrolment.
6. Blood donation within 3 months prior to enrolment
7. Planned in-patient hospitalization
8. Abuse of drugs or alcohol or any other condition associated with poor compliance
9. Previously enrolled in the present study
10. Participation in another clinical study within 90 days preceding enrolment
11. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at t

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to evaluate airway tissue availability of budesonide via Symbicort Turbuhaler and fluticasone via Seretide Diskus in severe COPD patients and healthy volunteers, using area under the curve (AUC) of the plasma concentrations of the steroid components as surrogate marker.;Secondary Objective: In addition to the primary objective there is a number of planned exploratory analyses:<br>- to investigate the amount of fluticasone and budesonide (% of delivered dose)<br>spontaneously expectorated in sputum.<br>- to investigate correlation between weight of spontaneously expectorated sputum<br>and AUC for budesonide and fluticasone.<br>- to investigate correlation between baseline lung function in COPD patients and<br>AUC for plasma concentrations of budesonide and fluticasone;Primary end point(s): The primary variable is AUC for fluticasone and budesonide plasma concentrations in COPD patients and healthy volunteers.