A Single Dose PD & PK Study With Two Formulations of Abediterol in Patients With Asthma
A Single Dose PD & PK Study With Two Formulations of Abediterol in Patients With Asthma
The purpose of this study is to investigate the pharmacodynamics of single doses of
 abediterol given by 2 different devices in participants with asthma. Abediterol (AZD0548) is
 a potential for once daily treatment of asthma and chronic obstructive pulmonary disease
 (COPD) in fixed dose combination (FDC) with an inhaled corticosteroid (ICS) or a novel
 anti-inflammatory agent. The aim of the clinical studies is to enable further investigations
 in participants with asthma and COPD to evaluate and develop abediterol as an effective long
 acting bronchodilator with an acceptable safety profile compared to other inhaled
 bronchodilators on the market, for the treatment of asthma and COPD.
This is a randomised, double-blinded, double-dummy, placebo-controlled, multi-centre, six-way
 William's design, crossover study to assess the pharmacodynamics, pharmacokinetics, and
 safety of abediterol single dose, given by dry powder inhaler or pressurised metered-dose
 inhaler, in patients with asthma, on inhaled corticosteroids. During the screening period,
 all patients will take their own baseline inhaled corticosteroid for 2 weeks. Patients on
 long-acting β2-agonist/ inhaled corticosteroids will be switched over to the respective
 inhaled corticosteroid monocomponent. Patients will be provided salbutamol as rescue
 medication for use throughout the study. Abediterol is an investigational product in early
 stages of clinical development, therefore individual participants in the clinical studies may
 not have a clinical benefit, especially in view of alternative therapies (bronchodilators)
 being available for the treatment of asthma and COPD.
Inclusion Criteria:

 1. Provision of informed consent before any study specific procedures.

 2. Men or non-pregnant, non-lactating women 18 to 75 years of age, inclusive.

 3. Non-smoker or ex-smoker (quit ≥6months prior to Visit 1) with a total smoking history
 of ≤10 pack years.

 4. Documented clinical diagnosis of asthma for ≥6 months before Visit 1 according to GINA
 guidelines.

 5. On stable dose of ICS or ICS/LABA FDC, for at least 1 month prior to Visit 1, at the
 doses approved in the country of enrolment.

 6. Prebronchodilator FEV1 at Visit 2 ≥40% and ≤85% of predicted (1 repetition of the test
 is allowed before screen failure).

 7. Reversibility to salbutamol (per American Thoracic Society (ATS)/European Respiratory
 Society (ERS) criteria, 2005 ie, ≥12% and ≥200 mL) at Visit 2 (1 repetition of the
 test is allowed before screen failure).

 8. Demonstrate the ability to use the study inhalation device properly.

 9. Able to perform repeated pulmonary function testing for FEV1.

 10. Able to read, speak and understand German.

 11. Patient must agree to all restrictions during the study.

 Exclusion Criteria:

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

 2. Participation in another clinical study with an IP during the last 3 months.

 3. Known or suspected hypersensitivity to the IP or excipients, including lactose (Note:
 lactose intolerance is not an exclusion).

 4. Systemic steroid use in the 6 weeks before Visit 1.

 5. Hospitalization due to asthma in the 6 months prior to Visit 1.

 6. Any active pulmonary disease other than asthma.

 7. Non-compliance with study procedures in the run in period - as judged by the
 Investigator.

 8. Treatment with biologicals such as monoclonal antibodies or chimeric biomolecules
 including omalizumab within 6 months or 5 half-lives before Visit 1 (whichever is
 longer).

 9. Treatment with any investigational drug within 30 days or 5 half-lives (whichever is
 longer) prior to Visit 1.

 10. Plasma donation within 1 month of screening or any blood donation/loss more than 500
 mL during the 3 months prior to Visit 1.

 11. Any laboratory abnormality or suspicion of any clinically relevant disease or disorder
 (on history or examination), including uncontrolled hypertension or uncontrolled
 diabetes, which, in the opinion of the Investigator, may either put the patient at
 risk because of participation in the study, or influence the results or the patient's
 ability to participate in the study, or any other safety concerns in the opinion of
 the Investigator.

 12. Known chronic hepatitis or HIV infections at the time of enrolment.

 13. Any active malignancy or treatment thereof within the 3 years prior to enrolment.

 14. Any clinically important abnormalities in rhythm, conduction, or morphology of the
 screening 12-lead ECG as judged by the Investigator on the screening ECG.

 15. Prolonged QT interval using Fridericia's correction 450 msec for males and 470 msec
 for females on the screening ECG or family history of long QT syndrome.

 16. PR (PQ) interval prolongation (> 240 msec), intermittent second or third degree
 atrialventricular (AV) block or AV dissociation on the screening ECG.

 17. Implantable cardiac defibrillator and patients with sustained symptomatic ventricular
 and/or atrial tachyarrhythmia.

 18. Any contraindication against the use of sympathomimetic drugs as judged by the
 Investigator.

 19. Unstable angina pectoris or stable angina pectoris classified higher than Canadian
 Cardiovascular Society Class II, or a myocardial infarction, or stroke within 6 months
 before Visit 1.

 20. History of hospitalisation within 12 months caused by heart failure or a diagnosis of
 heart failure higher than New York Heart Association Class II.

 21. Suspected poor capability to follow instructions of the study, as judged by the
 Investigator.

 22. History of or current alcohol or drug abuse (including marijuana), as judged by the
 Investigator.

 23. Planned in-patient surgery, major dental procedure or hospitalisation during the
 study.

 24. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff,
 contract research organisation staff and/or staff at the study site).

 25. Vulnerable persons (eg, persons kept in detention). 26 Daily rescue medication
 (salbutamol) use of ≥ 12 puffs for ≥ 3 consecutive days during the run-in period.

 27. Patient who intends to use any concomitant medication not permitted by this protocol or
 not to meet the restrictions.

 28. Patient on treatment with strong CYP3A4 inhibitors such as ketoconazole or itraconazole
 or CYP3A4 inducers such as rifampin at Visit 1.

 29. Procedures for withdrawal of incorrectly enrolled patients.