| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Obstructive Pulmonary Disease (COPD) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010952 |
| E.1.2 | Term | COPD |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the dose-response relationship and efficacy of AZD9668 at 3 dose levels compared with placebo in symptomatic COPD patients by assessing effects on lung function and symptoms of COPD. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate safety and tolerability of AZD9668 in COPD patients
To confirm AZD9668 exposure in plasma
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Provision of written informed consent prior to any study specific procedures at visit 1a
2. Male or female subject (females subject may of non-child bearing potential (i.e. postmenopausal or surgically sterile) or of child bearing potential):
- Women will be considered post menopausal if tehy are i) over 50 years old and have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment or ii) over 57 years old
- Surgically aterile 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 females 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 birt control. Further details of methods of birth control that are considered suitable for use are given in Section 6.1
3. Aged 40-80 years inclusive at visit 1b
4. Documented clinical diagnosis of COPD, according to Global Initiative on Obstructive Lung Disease (GOLD) guidelines (GOLD 2008) with symptoms for ≥ 1 year before visit 1b
5. History of at least one COPD exacerbation, requiring a course of oral or parenteral steroids and/or antibiotics within 4 weeks to 12 months before visit 1b
6. Current or ex-smokers with a smoking history of at ≥ 10 pack years (1 pack year = tobacco consumption corresponding to 20 cigarettes smoked per day for one year) at visit 1a
7. FEV1 40 - 80% (inclusive) of the predicted normal value post-bronchodilator as assessed at visit 1b
8. FEV1/FVC <70% post-bronchodilator at visit 1b
9. Able to use the handheld electronic devices (assessed at visit 1a)
10. Total COPD symptom score ≥ 2 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)
11. Complete morning recordings of daily FEV1 data at least 10 days of the last 14 days before visit 2
|
|
| E.4 | Principal exclusion criteria |
1.Any clinically relevant disease or disorder e.g. 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 patient at risk because of participation in the study, or may influence the results of the study, or the patient’s ability to participate in the study
2. Significant or unstable ischemic 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. Patients 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 any 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 patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient’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 patient 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. Alanine aminotransferase (ALT) / aspartate aminotransferase (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 non-investigational study drugs provided for the study (tiotropium 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 defined by national guidelines) or known drug abuse
19. Scheduled in patient surgery or hospitalisation during the course of the study
20. Patients scheduled for an intensive COPD rehabilitation program (patients who are in the maintenance phase of a rehabilitation program are eligible to take part)
21. Patients with conditions that may worsen if treated with tiotropium, according to the prescribing information for tiotropium in each participating country
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Pre-bronchodilator FEV1 measured at clinic visits
Lung function: Post-bronchodilator FEV1 measured at clinic visits, Pre- and post-bronchodilator FVC and IC measured at clinic visits, PEF and FEV1 measured at home by the patient
Signs and symptoms: EXACT, BCSS, Sputum colour assessed using Bronkotest© 5-point colour scale, Use of reliever medication
Exercise capacity:6MWT
Health Related Quality of Life:SGRQ-C, FPI - SF (exploratory endpoint aligned to primary objective)
Exacerbations:Exacerbations (including antibiotic use and/or systemic steroid use (oral or parenteral) and/or emergency room treatment and/or hospitalisation)
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 26 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the entire study is defined as "the last visit of the last patient undergoing the trial". |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 13 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 13 |
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