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 |
The primary objective of the study is to investigate the pharmacodynamics of inhaled AZD9164 compared to placebo and tiotropium. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: • To investigate the safety of single-doses of AZD9164 • To investigate drug exposure of AZD9164 The exploratory objective of the study is: • To collect and store DNA for possible future exploratory research into genes/genetic variation that may influence response to AZD9164 (ie, distribution, safety, tolerability and efficacy) and/or susceptibility to COPD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of signed and dated ICF prior to any study specific procedures. 2. Men or post-menopausal women (defined as amenorrheic for 12 months and FSH plasma concentration within the post-menopausal range as defined by the laboratory) or surgically sterile woman. 3. Be aged 40 years or above at Visit 1. 4. Have a body mass index (BMI) ≥ 19 kg/m2 and weigh ≥ 50 kg. 5. A clinical diagnosis of COPD no later than Visit 1, with symptoms for more than 1 year. 6. FEV1 40 - 80% of the predicted normal value (post-bronchodilator) and post-bronchodilator FEV1/FVC < 70%. 7. Current or ex-smokers with a smoking history of ≥ 10 pack years (1 pack year equals 20 cigarettes smoked per day for 1 year). 8. Chest radiography (not older than 6 months prior to Visit 1) not showing any pathological changes that would make the subject unsuitable for inclusion as judged by the Investigator. 9. Reversible airway obstruction, tested according to routines at the clinic. A minimum of ≥ 10% increase in FEV1 to 3 x 40 µg ipratropium at 2 occasions separated by at least 1 day. 10. Be able to inhale from a Spira nebuliser and a HandiHaler ® device. |
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E.4 | Principal exclusion criteria |
1. Symptoms of any clinically significant illness within 2 weeks prior to Visit 4. 2. An exacerbation of COPD (defined as use of systemic antibiotics and/or systemic glucocorticosteroids (GCS) and/or hospitalisation related to COPD) within 30 days of Visit 1. 3. Any clinically significant disease or disorder (eg 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 subject at risk because of participation in the study, or influence the result of the study, or the subject’s ability to participate in the study. 4. Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, ECG or lung function at baseline, which, in the opinion of the Investigator, may put the subject at risk because of his/her participation in the study. 5. The use of concomitant medications that prolong the QT/QTc interval other than inhaled ß2-agonists, eg, certain antihistamines, anti-arrhythmics, tricyclic antidepressants and monoamine oxidase inhibitors. 6. QTcF > 450 ms or QT > 500 ms at Visit 2. 7. Treatment with systemic GCS within 30 days of Visit 4. 8. History of current clinically relevant arrhythmia, heart block, intraventricular conduction delay or other clinical relevant ECG abnormalities, or unstable angina, New York Heart Association (NYHA) Class III-IV heart failure, as judged by the Investigator. 9. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This includes subjects with any of the following: - PR interval >200 ms (first degree AV block) - Intermittent second or third degree AV block - Dropped beats - Incomplete, full or intermittent bundle branch block (QRS <110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy) - Abnormal T wave morphology, particularly in the protocol defined primary lead 10. Any definite or suspected personal history of intolerance or hypersensitivity to drugs and/or their excipients (including lactose, ipratropium, tiotropium or other anticholinergics), judged to be clinically relevant by the Investigator. 11. History of significant urinary retention or bladder neck obstruction. 12. Donation of blood within 3 months or donation of plasma within 14 days prior to Visit 1. 13. History of current alcohol or drug abuse, as judged by the Investigator. 14. A suspected/manifested infection according to International Airline Transportation Association (IATA) (see CSP Appendix C for further information). 15. Need of long term oxygen therapy (LTOT) and/or saturation O2 < 92%. 16. Positive results on screening tests for hepatitis B and/or C and/or HIV. 17. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at the investigational site). 18. Participation in any clinical study with an investigational drug or new formulation of a marketed drug within 3 months prior to Visit 4. 19. Participation in a methodology study (in which no drugs are administered), during the study period, that may interfere with the results of this study, as judged by the Investigator. 20. Planned in-patient surgery or hospitalisation during the study. 21. Subjects who, in the opinion of the Investigator, should not participate in the study. 22. Previous randomisation in the present study. 23. Heredity for glaucoma or symptoms of narrow angle glaucoma such as headache, serious eye pain or halo phenomena in the evening or at night. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable for local pulmonary effect is Forced Expiratory Volume in 1 second (FEV1). This will be assessed through the average effect over 24 hours (Eav), maximum effect (Emax) and average effect over 22-26 hours (E22-26). The variables for systemically mediated effects will be heart rate, QTc, pulse and blood pressure. |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | 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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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
| |
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 | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 5 |