A Single Dose PD & PK Study With Two Formulations of Abediterol in Patients With Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Abediterol 0.156 μg; Abediterol 2.5 μg; Abediterol 0.05 μg; Abediterol 0.156 μg; Abediterol 2.5 μg; Placebo
Intervention description: Dry powder for inhalation; Dry powder for inhalation; Pressurised metered-dose inhaler; Pressurised metered-dose inhaler; Pressurised metered-dose inhaler; Pressurised metered-dose inhaler and dry powder for inhalation.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Abediterol; Dry powder inhaler; Pressured metered-dose inhaler; Pharmacokinetic; Pharmacodynamic; Safety

Summary:

      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.
    

Eligibility criteria:

        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.