A 12-month, double-blind, double-dummy, randomized, parallel group, multicenter efficacy and safety study of Symbicort® pMDI 2x160/4.5µg bid and 2x80/4.5 µg bid compared to Formoterol Turbuhaler 2x4.5µg bid and Placebo in patients with chronic obstructive pulmonary disease (COPD). - S

Phase 1

• Conditions: This is an application for a phase III study to be conducted in COPD patients.; Classification code 10010952

• Registration Number: EUCTR2004-001168-28-DK
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2004-11-25
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1600

Inclusion Criteria

1. Signed written informed consent from the patient.
2. Outpatients, men or women >= 40 years of age.
3. Clinical diagnosis of COPD, with COPD symptoms for more than 2 years.
4. Smoking, current or previous, with a smoking history >= 10 pack years.
5. Pre-bronchodilatory FEV1 £50% of predicted normal value.
6. Pre-bronchodilatory FEV1/VC <70 %
7. Documented use of short-acting inhaled bronchodilatator (ß2-agonist or anticholinergics) as rescue medication.
8. A score of at least one COPD exacerbation requiring a course of oral steroids and/or antibiotics within 1-12 months prior to Visit 1 (ie, not within the 30 days prior to Visit 1).
9. Total symptom score of 2 or more per day for at least half of the run-in period (by totalling the Breathlessness Diary, cough and sputum scores from the diary card).
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

1. A history of asthma (National Institutes of Health 2002).
2. A history allergic rhinitis before 40 years of age.
3. 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.
4. Any current respiratory tract disorders other than COPD, which is considered by the investigator to be clinically significant.
5. Known homozygous Alpha-1 antitrypsin deficiency.
6. 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.
7. Patients who have needed additions or alterations to their usual maintenance or rescue therapy for COPD due to worsening symptoms within the 30 days prior to Visit 1.
8. Use of oral or ophthalmic non-cardio-selective b-blocking agents.
9. Use of oral steroids.
10. Participation in a COPD rehabilitation program within 6 months prior to the study or who are scheduled for such a programme during the study.
11. Known or suspected hypersensitivity to study therapy or excipients.
12. Scheduled in-patient hospitalisation during the course of the study.
13. Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator. Female patients who are not post-menopausal or surgically sterile must have a negative pregnancy test prior to randomisation.
14. Participation in a clinical study evaluating an investigational drug in the last 30 days prior to Visit 1, or previous allocation of a randomisation code in this study (if a patient has previously been enrolled, fulfilled all the inclusion criteria and none of the exclusion criteria at Visit 1, but was not eligible to be randomized due to worsening COPD symptoms in the run-in period, the patient may be enrolled into the study a second time).
15. Previous participation in a Symbicort pMDI clinical study.
16. A history of any condition associated with poor compliance.
17. Involvement in the planning or conduct of the study (applies to both AstraZeneca staff and staff at the Investigator site).
18. At Visit 2: patient who have needed additions or alterations to their usual maintenance or rescue therapy for COPD due to worsening symptoms since Visit 1.
19. In the ophthalmologic assessment sub-group: inability to dilate pupil 6mm or more.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy (pre-/post dose FEV1) of Symbicort® pMDI (pressurised Metered Dose inhaler) 2x 160/4.5µg/inhalation twice daily and of Symbicort® pMDI 2x 80/4.5µg/inhalation twice daily to formoterol Turbuhaler 2x4.5µg/inhalation twice daily and placebo, over a 12-month period in patients with COPD.;Secondary Objective: To evaluate efficacy for a number of secondary variables (e.g. dyspnea, QoL, exacerbations) and safety (e.g. AE, ECG, urinary cortisol, ophtalmology, bone mineral density, hematology, clinical chemistry) of budesonide and formoterol. ;Primary end point(s): Pre-dose FEV1 and 1 hour post-dose FEV1.