A Phase 1 study to assess pharmacokinetics (PK) and safety of abediterol 5 μg dry powder inhaler (DPI) given once daily (QD) for 9 days, compared to placebo, in patients with asthma on inhaled corticosteroids (ICSs).
This is a randomized, single-blind, placebo-controlled study to assess PK and safety of abediterol 5 μg DPI given QD for 9 days, compared to placebo, in patients with asthma on ICSs. It is planned that 12 patients with asthma will be randomized into the study, of which 9 will receive abediterol 5 μg and 3 will receive placebo. The entire study period is scheduled to take a maximum of 41 days (follow-up included) for each individual patient. During the screening period, all patients will take their own baseline inhaled corticosteroids. Patients on long-acting β2-agonist/inhaled corticosteroids will be switched over to the respective inhaled corticosteroid mono-component at Visit 1. Patients will be provided salbutamol as rescue medication for use throughout the study. Each patient will receive a single inhaled dose of abediterol or placebo in the morning of Days 1 to 9 (Visits 3 to 8) under supervision of the Investigator or designee.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
12
A β2-adrenoceptor agonists, produce smooth muscle relaxation in the airways and improves lung function.
Abediterol matching placebo without any pharmacological activity.
Research Site
Berlin, Germany
Observed maximum plasma concentration (Cmax) assessment for abediterol on Day 1
To assess Cmax after single inhaled dose of abediterol 5 μg. Cmax will be taken directly from the individual concentration-time curve.
Time frame: Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours
Time to reach maximum plasma concentration (tmax) assessment for abediterol on Day 1
To assess tmax after single inhaled dose of abediterol 5 μg. tmax will be taken directly from the individual concentration-time curve.
Time frame: Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours
Area under the plasma concentration-curve from time zero to the time of last quantifiable concentration (AUClast) assessment for abediterol on Day 1
To assess AUClast after single inhaled dose of abediterol 5 μg.
Time frame: Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours
Area under the plasma concentration-curve from time zero to 24 hours post-dose (AUC(0-24)) assessment for abediterol on Day 1
To assess AUC(0-24) after single inhaled dose of abediterol 5 μg.
Time frame: Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours
Observed maximum concentration (Cmax) assessment for abediterol on Day 9
To assess Cmax after multiple once daily inhaled doses of abediterol 5 μg. Cmax will be taken directly from the individual concentration-time curve.
Time frame: Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Time to reach maximum concentration (tmax) assessment for abediterol on Day 9
To assess tmax after multiple once daily inhaled doses of abediterol 5 μg. tmax will be taken directly from the individual concentration-time curve.
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Time frame: Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Terminal rate constant, estimated by log-linear LS regression of the terminal part of the concentration-time curve (λz) assessment for abediterol on Day 9
To assess λz after multiple once daily inhaled doses of abediterol 5 μg.
Time frame: Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Terminal half-life, estimated as (ln2)/λz (t½λz) assessment for abediterol on Day 9
To assess t½λz after multiple once daily inhaled doses of abediterol 5 μg.
Time frame: Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Area under the plasma concentration-curve from time zero to the time of last quantifiable concentration (AUClast) assessment for abediterol on Day 9
To assess AUClast after multiple once daily inhaled doses of abediterol 5 μg.
Time frame: Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Area under the plasma concentration-curve from time zero to 24 hours post-dose (AUC(0-24)) assessment for abediterol on Day 9
To assess AUC(0-24) after multiple once daily inhaled doses of abediterol 5 μg.
Time frame: Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Apparent clearance for drug estimated as dose divided by AUC0-24 (CL/F) assessment for abediterol on Day 9
To assess CL/F after multiple once daily inhaled doses of abediterol 5 μg.
Time frame: Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Average plasma concentration during a dosing interval, estimated as AUC0-24/24 (Cavg) assessment for abediterol on Day 9
To assess Cavg after multiple once daily inhaled doses of abediterol 5 μg.
Time frame: Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Fluctuation index during a dosing interval estimated as 100*(Cmax - Cmin)/Cavg (%), where Cmin is the minimum concentration at the end of the dosing interval (%Fluctuation) assessment for abediterol on Day 9
To assess %Fluctuation after multiple once daily inhaled doses of abediterol 5 μg.
Time frame: Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Accumulation ratio for Cmax estimated as (Cmax on Day 9/Cmax on Day 1) (Rac (Cmax)) assessment for abediterol on Day 9
To assess Rac (Cmax) after multiple once daily inhaled doses of abediterol 5 μg.
Time frame: Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours; Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Accumulation ratio for AUC0-24 estimated as (AUC0-24 on Day 9/AUC0-24 on Day 1) (Rac (AUC0-24)) assessment for abediterol on Day 9
To assess Rac (AUC0-24) after multiple once daily inhaled doses of abediterol 5 μg.
Time frame: Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours; Day 9: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours
Vital sign (Blood pressure [BP])
Systolic and diastolic BP (in mmHg) will be measured after the patient has rested in the supine position for at least 5 minutes and before taking any blood sample and conducting any spirometry.
Time frame: Change from baseline up to Day 13
Vital sign (pulse)
Pulse (beats per minute \[bpm\]) will be measured after the patient has rested in the supine position for at least 5 minutes and before taking any blood sample and conducting any spirometry.
Time frame: Change from baseline up to Day 13
12-lead Electrocardiograms (ECGs) including high precision QTc analysis and telemetry
12-Lead ECG results performed for safety evaluation will be listed for each patient and will include the ECG parameters (where applicable \[Screening, pre-dose Day 1 and Follow-up\]) and changes from baseline, assessment by the Investigator (normal/abnormal not clinically significant/abnormal clinically significant) and details of any abnormalities (rhythm, ectopy, conduction, morphology, myocardial infarction, ST segment, T wave and U wave observations).
Time frame: Change from baseline up to Day 13
Clinical laboratory assessments (hematology, clinical chemistry and urinalysis)
Hematology and clinical chemistry values (including serial potassium and glucose) will be listed by patient and time point including changes from baseline (pre-dose Day 1) and repeat/unscheduled measurements. Urinalysis will include glucose, protein, blood, leucocytes, flow cytometry, microscopy.
Time frame: Change from baseline up to Day 11
Number of patients with Adverse Events (AEs)
An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver) or the abnormal results of an investigation (e.g., laboratory findings, electrocardiogram). In clinical studies an AE can include an undesirable medical condition occurring at any time after the patient has signed informed consent, including run-in or washout periods, even if no specific treatment has been administered.
Time frame: Change from baseline up to follow-up (14 ± 2 days post (final) dose)