A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multinational, Phase IIb Study to Evaluate the Efficacy and Safety of 60 mg AZD9668 Administered Orally Twice Daily to Subjects with Chronic Obstructive Pulmonary Disease (COPD) on Treatment with budesonide/formoterol - MISTRAL

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-014586-75-HU
• Date of registration: 28/09/2009
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multinational, Phase IIb Study to Evaluate the Efficacy and Safety of 60 mg AZD9668 Administered Orally Twice Daily to Subjects with Chronic Obstructive Pulmonary Disease (COPD) on Treatment with budesonide/formoterol - MISTRAL
• Scientific title: A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multinational, Phase IIb Study to Evaluate the Efficacy and Safety of 60 mg AZD9668 Administered Orally Twice Daily to Subjects with Chronic Obstructive Pulmonary Disease (COPD) on Treatment with budesonide/formoterol - MISTRAL
• Date of first enrolment: 21/12/2009
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-014586-75
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Bulgaria, Czech Republic, Hungary, Slovakia

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of written informed consent prior to any study specific procedures at visit 1a

2. Male, or female subjects (female subjects may be of non-childbearing potential (ie, post menopausal or surgically sterile) or of child bearing potential):
- Women will be considered post menopausal if they are i) over 50 years old and have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments or ii) over 57 years old
- Surgically sterile is defined as having undergone hysterectomy and/or bilateral oophrectomy and/or bilateral salpingectomy; tubal ligation on its own is not adequate
- Women will be considered of child bearing potential if they are between menarche and menopause, and have not been permanently or surgically sterilised. All female subjects must have a serum pregnancy test at visit 1b and visit 7. Women of child bearing potential must undergo an additional urine pregnancy test at visit 2 prior to randomisation and must be using suitable methods of birth control. Further details of methods of birth control that are considered suitable for use are given in Section 5.1

3. Aged 40-80 years inclusive

4. Documented clinical diagnosis of COPD, according to GOLD guidelines with symptoms for ³1 year before visit 1b

5. Subjects who have received ICS as monotherapy or in combination with any long acting bronchodilator in the last 3 months

6. History of a least one COPD exacerbation, requiring a course of oral parenteral steroids and/or antibiotics within 4 weeks to 12 months before visit 1b

7. Current or ex-smokers with a smoking history of at least 10 pack years (1 pack year = tobacco consumption corresponding to 20 cigarettes smoked per day for one year)

8. FEV1/FVC <70% post-bronchodilator at visit 1b

9. FEV1 =30 and <80% of the predicted normal value post-bronchodilator at visit 1b (GOLD stage II/III)

10. Able to use the handheld electronic devices

11. Total COPD symptom score ³2 per day for at least 7 days of the last 14 days before visit 2 (by totalling breathing, cough and sputum scores from the BCSS diary card)

12. Complete morning recordings of daily FEV1 data at least 10 days of the last 14 days of the run-in period
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. Any clinically relevant disease or disorder eg, infectious/viral disease (including hepatitis B or C) cardiovascular, pulmonary other than COPD, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment, past or present, 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.

2. Significant or unstable ischaemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension, or any other relevant cardiovascular disorder as judged by the Investigator

3. Current diagnosis of asthma according to Global Initiative for Asthma (GINA) guidelines (GINA 2008)

4. Malignancy or neoplastic disease within the past 5 years other than treated basal/squamous cell skin carcinoma or treated cervical cancer in situ

5. Subjects who require long term oxygen therapy (LTOT)

6. Worsening of COPD within 4 weeks prior to visit 1b and during the run-in period (defined as an increase in respiratory symptoms requiring hospitalisation and/or a course of oral glucocorticosteroids and/or increased usage/dose of inhaled steroids and/or antibiotic treatment)

7. Acute infections requiring treatment in the 4 weeks prior to visit 1b and during the run-in period

8. Any clinically relevant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis at visit 1b, which in the opinion of the Investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject’s ability to participate in the study

9. A QTcB interval of >450 msec for males and >470 msec for females at visit 1b

10. Any ECG abnormality (including arrhythmia), which in the opinion of the investigator may put the subject at risk or interfere with study assessments at visit 1b

11. A past history of or current clinical or laboratory evidence of renal failure, or an estimated creatinine clearance of <50 mL/min (as calculated by the Cockcroft-Gault formula) at visit 1b

12. ALT or AST level = 1.5 x upper limit of normal (ULN) at visit 1b

13. Pregnancy, breast-feeding or planned pregnancy during the study

14. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

15. Previous randomisation to treatment in the present study

16. Known or suspected hypersensitivity to the investigational product or excipients or additional study drugs provided for the study (budesonide/formoterol and reliever medication)

17. Participation (defined as administration of at least one dose of investigational product) in another clinical study, the last follow-up visit of which is within 12 weeks of visit 1b in this study

18. Excessive alcohol consumption (as judged by the Investigator) or known drug abuse

19. Previous participation in a study with AZD9668

20. Scheduled elective surgery or hospitalisation during the course of the study

21. Subjects scheduled for an intensive COPD rehabilitation program (subjects who are in the maintenance phase of a rehabilitation program are eligible to take part)

22. Subjects with any contraindications to the use of budesonide/formoterol, according to the prescribing information in each participating country


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease
MedDRA version: 12.0 Level: LLT Classification code 10010952 Term: COPD

Intervention(s)

Product Name: AZD9668
Product Code: AZD9668
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: none
CAS Number: none
Current Sponsor code: AZD9668
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Trade Name: Symbicort forte Turbuhaler
Product Name: Symbicort
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: FORMOTEROL FUMARATE
CAS Number: 43229-80-7
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 9-
INN or Proposed INN: BUDESONIDE
CAS Number: 51333-22-3
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 320-

Primary Outcome(s)

Main Objective: To evaluate the efficacy of AZD9668 compared with placebo in symptomatic COPD subjects by assessing effect on lung function and symptoms of COPD.

Secondary Objective: To evaluate safety and tolerability of AZD9668 in COPD subjects.

Primary end point(s): Pre-bronchodilator FEV1 measured at clinic visits

Lung function: FEV1 at clinic visits, (post-bronchodilator), Pre and post-bronchodilator FVC, FEV6 FEF25-75% and IC at clinic visits, PEF and FEV1 measured at home by the subject

Signs and symptoms: EXACT, BCSS, Sputum colour assessed using Bronkotest© 5-point colour scale, Use of reliever medication

Exercise capacity: ISWT (including Borg), ESWT (including Borg)

Health Related Quality of Life: SGRQ-C

Exacerbations: Exacerbations (including antibiotic use and/or systemic steroid use (oral or parenteral) and/or emergency room treatment and/or hospitalisation)

Secondary ID(s)

D0520C00020