E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic obstructive pulmonary disease (COPD) |
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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 |
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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 |
1. To investigate the tolerability of 14 days’ dosing with AZD9668 in patients with COPD, as measured by vital signs, ECG, lung function, haematology, clinical chemistry, urinalysis and adverse event reporting.
2. To determine the plasma pharmacokinetics and renal clearance of AZD9668 in patients with COPD.
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E.2.2 | Secondary objectives of the trial |
1. To assess the effect of orally administered AZD9668 on neutrophils in induced sputum of patients with COPD.
2. To investigate the effects of AZD9668 on sputum bacteriology.
3. To measure the concentration of AZD9668 in induced sputum following oral administration.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Be willing and able to comply with study procedures and provide written informed consent
2. Be male or post-menopausal (for more than 12 months)/surgically sterile female between 40 and 80 years
3. Have a clinical diagnosis of COPD
4. Smokers or ex-smokers (with at least 10 pack years)
5. Post-bronchodilator FEV1 30 - 80% predicted, FEV1/FVC ratio < 70% (GOLD stage II to III, GOLD 2007)
For inclusion in this genetic research, patients must fulfil the following criterion: 1. Provision of informed consent for genetic research
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E.4 | Principal exclusion criteria |
1. Concomitant diagnosis of significant pulmonary disease other than COPD, including symptomatic asthma, cystic fibrosis and allergic bronchopulmonary aspergillosis
2. An acute exacerbation (defined as an increase in respiratory symptoms requiring hospitalisation and/or a course of oral glucocorticosteroids and/or antibiotics, either prescribed or self administered); or acute respiratory infection (upper or lower) in the 4 weeks prior to Visit 1 or Visit 2
3. Use of oral corticosteroids in the 8 weeks prior to Visit 2 (use of inhaled corticosteroids is allowed)
4. Use of antibiotics, systemically or nebulised, in the 4 weeks prior to Visit 1 or Visit 2
5. Current requirement for oxygen therapy
6. Any other clinical disease or disorder (including insulin-dependent diabetes) 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
7. Positive test result for HIV, Hepatitis B or C
8. Scheduled in-patient surgery or hospitalisation during the course of the study
9. Previous randomisation into the present study
10. Participation in another clinical study involving an investigational product within 4 weeks or 5 times the half life, whichever is longer, of Visit 1
11. A past history of or current clinical or laboratory evidence of renal disease, or a calculated creatinine clearance (Cockcroft-Gault formula) of ≤70 ml/min at Visit 1
12. (a) QTc >450 ms for males and >470 ms for females in the screening ECG
(b) The presence of any arrhythmia in the ECG at Visit 1. which in the opinion of the investigator may put the patient at risk or interfere with study assessments. (Premature ventricular or supraventricular ectopics up to 6/minute will be allowed at the investigators discretion, as long as there are no other associated cardiac abnormalities)
(c) Current or previous history of coronary artery disease, or congestive cardiac failure or any other clinically significant cardiac disease
13. Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, ECG or lung function at Visit 1, 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.
14. Patients who, in the opinion of the investigator, should not participate in the study.
15. History of excessive alcohol consumption or chronic alcohol induced disease. Excessive alcohol consumption will be defined as the consumption >28 units/week in males or >21 units in females [1 unit is equivalent to half a pint (285 ml) of beer, 1 glass (125 ml) of wine or 1 measure (25 ml) of spirits].
16. If participation in the study would result in the volunteer donating more than 1350 mL of blood in the 12 months or 500 mL of blood in the 3 months before the end of the study
17. The patient is not able to understand and comply with protocol requirements, instructions and protocol-stated restriction
18. Vulnerable patients (e.g. persons kept in detention).
19. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
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E.5 End points |
E.5.1 | Primary end point(s) |
Tolerability: Adverse events, vital signs, ECG, lung functions, haematology, clinical chemistry, and urinalysis.
Pharmacokinetic: AZD9668 plasma and urine concentrations Day 1: Cmax, tmax, AUC(0-t), AUC(0-24), C24, AUC, t1/2, CL/F, Vz/F, CLR, Ae and Fe (%) Day 7: Cmin,ss Day 14: Cmin,ss, C,max,ss, tmax, AUC(0-t),ss, AUC(0-24),ss, C24,ss, AUCss, t1/2ss, CL/Fss, Vz/Fss, Rac, CLR, Ae,ss and Fe,ss (%)
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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The end of the trial is defined as the date of database lock |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |