| 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 |
Primary objective is:
• To compare the clinical efficacy of AZD3199 inhaled once daily with 9 μg
formoterol twice daily and placebo over a 4-week treatment period in adults with
chronic obstructive pulmonary disease (COPD) |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
• To investigate the safety of AZD3199 by assessment of the nature, incidence,
and severity of adverse events (AE), safety laboratory variables, pulse, blood
pressure, and ECG
• To investigate the effect of regular treatment with AZD3199 on the reversibility
in FEV1 after inhalation of salbutamol
• To determine the pharmacokinetics (PK) of AZD3199 in COPD patients
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For inclusion in the study patients must fulfil the following criteria:
1. Provision of informed consent prior to any study specific procedures
2. Men or women, aged ≥40 years. Women must be of non-childbearing potential or
must have used a highly effective contraceptive method for the last 3 months prior
to Visit 1 (the start date of the run-in period).
3. Clinical diagnosis of COPD, with symptoms for more than 1 year
4. Current or ex-smokers with a smoking history of at least 10 pack years
5. 40% ≤ FEV1 <80% of the predicted normal value (post-bronchodilator) and
post-bronchodilator FEV1/FVC < 70%
Randomization criteria at Visit 2:
6. Total AZ COPD symptom scores ≥2 per day for at least half the number of days of
the run-in period (by totalling the breathlessness, cough, chest tightness and night
time awakening scores from the diary)
7. FEV1 pre-bronchodilator must be reproducible within a maximum of 8 attempts
For voluntary participation in the genetic part of the study:
8. Provision of informed consent for genetic part of the study
|
|
| E.4 | Principal exclusion criteria |
Patients must not enter the study if any of the following exclusion criteria are fulfilled:
1. Current or a history of asthma
2. A history of atopic disease, such as allergic rhinitis, before 40 years of age
3. Any current respiratory tract disorder other than COPD, including respiratory
diseases described in GOLD 2008 or JRS Guidelines 2004 as needed to be
differentiated from COPD, which is considered by the investigator to be clinically
significant
4. Significant disease or disorder (e.g. cardiovascular, pulmonary other than COPD,
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 influence the results of the study, or the patient’s ability to participate in the study
5. Any clinically relevant abnormal findings in clinical chemistry, haematology,
urinalysis, physical examination, pulse, blood pressure or ECG at Visit 1, which,
in the opinion of the investigator, may put the patient at risk because of his/her
participation in the study
6. Body mass index (BMI) <18 kg/m2 or a body weight <30 kg
7. A marked baseline prolongation of QT and/or QTcF (QTcF interval > 450 ms or
QT > 500 ms for both males and females)
8. A history of additional risk factors for Torsade de Pointes (eg, heart failure,
hypokalemia, family history of Long QT syndrome)
9. Requirement for regular oxygen therapy
10. An exacerbation of COPD (defined as use of systemic antibiotics and/or systemic
glucocorticosteroids and/or hospitalisation related to COPD) within 30 days of
Visit 1 (the start date of the run-in period)
11. Known or suspected hypersensitivity to study therapy or excipients of the
investigational product
12. Pregnancy or lactation
13. Past or present alcohol or drug abuse
14. Participation in another study involving blood donation (>500 ml) within 3 months
of Visit 1 (the start date of the run-in period)
15. A suspected/manifested infection according to IATA categories A and B
16. Participation in any clinical study with an investigational drug or new formulation
of a marketed drug in the 3 months prior to Visit 1(the start date of the run-in
period)
17. Planned in-patient surgery or hospitalisation during the study.
18. Previous enrolment into the present study
19. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
For voluntary participation in the genetic part of the study:
20. Previous bone marrow transplant
21. Whole blood transfusion within 120 days of the date of genetic sample collection |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary outcome variable is FEV1, assessed both with regard to maximum bronchodilation and to trough effects 24 h after the morning administration
• Efficacy variables are:
- FEV1
- FVC
- Patient reported outcomes (AZ COPD Symptom Scores, CCQ, SGRQ-C)
- Use of reliever medication
• Safety variables are:
- Adverse Events (AE)
- Safety laboratory assessments
- Pulse and Blood pressure
- ECG
• Pharmacokinetic variables are:
- Cmax and AUC0-24h post-dose (Visit 5) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| 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 | No |
| 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 trial is defined as "Last patient out (the last visit of the last patient undergoing the study)". |
|
| 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 | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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