Overview

This trial is active, not recruiting.

Condition asthma
Treatments abediterol 0.156 μg, abediterol 2.5 μg, abediterol 0.05 μg, placebo
Phase phase 1
Sponsor AstraZeneca
Start date June 2016
End date October 2016
Trial size 36 participants
Trial identifier NCT02777827, D6540C00002

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacokinetics/dynamics study
Intervention model crossover assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)
abediterol 0.156 μg
Dry powder for inhalation
(Experimental)
Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation).
abediterol 2.5 μg
Dry powder for inhalation
(Experimental)
Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).
abediterol 0.05 μg
Pressurised metered-dose inhaler
(Experimental)
Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).
abediterol 0.156 μg
Pressurised metered-dose inhaler
(Experimental)
Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).
abediterol 2.5 μg
Pressurised metered-dose inhaler
(Placebo Comparator)
Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation).
placebo
Pressurised metered-dose inhaler and dry powder for inhalation.

Primary Outcomes

Measure
Change from baseline in trough forced expiratory volume in 1 second (FEV1).
time frame: Post-dose IP administration on Day 1.

Secondary Outcomes

Measure
Percentage of participants achieving a ≥ 200 mL and ≥12% increase from baseline in peak FEV1.
time frame: Visit 3 to Visit 8.
Time to peak FEV1 at Day 1
time frame: Day 1
Observed maximum concentration, taken directly from the individual concentration-time curve (Cmax)
time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Time to maximum concentration (h), taken directly from the individual concentration-time curve (tmax).
time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Terminal rate constant, estimated by log-linear least square regression of the terminal part of the concentration-time curve (λz)
time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Terminal half-life (h), estimated as (ln2)/λz (t1/2λz).
time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast).
time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Area under the concentration-time curve from time zero extrapolated to infinity. AUC is estimated by AUClast + Clast/λz where Clast is the last observed quantifiable concentration (AUC)
time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Apparent plasma clearance for parent drug estimated as dose divided by AUC (CL/F).
time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz (Vz/F).
time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Mean residence time (h), calculated by AUMC/AUC, where AUMC is the area under the first moment-time curve (MRT).
time frame: Pre-dose, 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1.
Adverse events and serious adverse events
time frame: Up to 112 days (including the Screening Visit and follow-up contact).
Vital signs
time frame: Up to 112 days (including the Screening Visit and follow-up contact).
Electrocardiograms (ECGs)
time frame: Up to 112 days (including the Screening Visit and follow-up contact).
Physical examination findings
time frame: Up to 112 days (including the Screening Visit and follow-up contact).
Clinical laboratory assessments
time frame: Up to 112 days (including the Screening Visit and follow-up contact).
Time to peak FVC at Day 1
time frame: Day 1
Percentage of participants achieving a ≥ 200 mL and ≥12% increase from baseline in trough FEV1.
time frame: Visit 3 to Visit 8.
Change from baseline in peak FEV1.
time frame: Day 1
Change from baseline in peak FEV1 AUC0-24.
time frame: Day 1
Change from baseline in peak FEV1 AUC0-12.
time frame: Day 1
Change from baseline in peak FEV1 AUC0-6.
time frame: Day 1
Change from baseline in peak FEV1 AUC12-24.
time frame: Day 1
Change from baseline in peak FVC.
time frame: Day 1
Change from baseline in trough FVC.
time frame: Day 1
Change from baseline in peak FVC AUC0-24.
time frame: Day 1

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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.

Additional Information

Official title A Randomised, Double-Blinded, Double-Dummy, Placebo-Controlled, MultiCentre-, Six-Way, Crossover Study to Assess the Pharmacodynamics, Pharmacokinetics, and Safety of Abediterol Single Dose, Given by Dry Powder Inhaler (DPI) or Pressurised Metered-Dose Inhaler (pMDI), in Patients With Asthma on Inhaled Corticosteroids
Principal investigator Jutta Beier, Dr
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.