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Abediterol

Phase 1

Asthma | Small molecule | Respiratory |AstraZeneca PLC|Last Updated: Feb 13, 2018

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Trial Design

RandomizedPLACEBO_CONTROLLED
Total Trials1
Total Enrollment12

FDA Designations

No designations recorded

Clinical trial landscape

Abediterol · 2 trials · 2 indications

Phase 1 2
NCT03273127To Assess the Pharmacokinetics, Safety and Tolerability of Abediterol Administered Once Daily for 9 Days, in Patients With Asthma on Inhaled CorticosteroidsAsthma
COMPLETED12 Analytics
NCT02967159A Study to Evaluate the Disposition of Drug in Body and Safety After Administration of Single Inhaled Doses of Drugs Abediterol and AZD7594 Administered Alone, in Fixed Dose Combination and in Free Combination Using the Dry Powder Inhaler in Healthy Male ParticipantsChronic Obstructive Pulmonary Disease (COPD)
COMPLETED14 Analytics
PHASE1COMPLETED
To Assess the Pharmacokinetics, Safety and Tolerability of Abediterol Administered Once Daily for 9 Days, in Patients With Asthma on Inhaled Corticosteroids
AsthmaUnlock trial analytics
PHASE1COMPLETED
A Study to Evaluate the Disposition of Drug in Body and Safety After Administration of Single Inhaled Doses of Drugs Abediterol and AZD7594 Administered Alone, in Fixed Dose Combination and in Free Combination Using the Dry Powder Inhaler in Healthy Male Participants
Chronic Obstructive Pulmonary Disease (COPD)Unlock trial analytics

Study Endpoints

Primary Endpoints

Observed maximum plasma concentration (Cmax) assessment for abediterol on Day 1
Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours

To assess Cmax after single inhaled dose of abediterol 5 μg. Cmax will be taken directly from the individual concentration-time curve.

Time to reach maximum plasma concentration (tmax) assessment for abediterol on Day 1
Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours

To assess tmax after single inhaled dose of abediterol 5 μg. tmax will be taken directly from the individual concentration-time curve.

Area under the plasma concentration-curve from time zero to the time of last quantifiable concentration (AUClast) assessment for abediterol on Day 1
Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours

To assess AUClast after single inhaled dose of abediterol 5 μg.

Area under the plasma concentration-curve from time zero to 24 hours post-dose (AUC(0-24)) assessment for abediterol on Day 1
Day 1: pre-dose and post-dose at 5, 15, 30, 45 minutes and 1, 2, 3, 4, 6, 8, 12 and 24 hours

To assess AUC(0-24) after single inhaled dose of abediterol 5 μg.

Observed maximum concentration (Cmax) assessment for abediterol on Day 9
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

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 to reach maximum concentration (tmax) assessment for abediterol on Day 9
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

To assess tmax after multiple once daily inhaled doses of abediterol 5 μg. tmax will be taken directly from the individual concentration-time curve.

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
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

To assess λz after multiple once daily inhaled doses of abediterol 5 μg.

Terminal half-life, estimated as (ln2)/λz (t½λz) assessment for abediterol on Day 9
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

To assess t½λz after multiple once daily inhaled doses of abediterol 5 μg.

Area under the plasma concentration-curve from time zero to the time of last quantifiable concentration (AUClast) assessment for abediterol on Day 9
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

To assess AUClast after multiple once daily inhaled doses of abediterol 5 μg.

Area under the plasma concentration-curve from time zero to 24 hours post-dose (AUC(0-24)) assessment for abediterol on Day 9
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

To assess AUC(0-24) after multiple once daily inhaled doses of abediterol 5 μg.

Apparent clearance for drug estimated as dose divided by AUC0-24 (CL/F) assessment for abediterol on Day 9
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

To assess CL/F after multiple once daily inhaled doses of abediterol 5 μg.

Average plasma concentration during a dosing interval, estimated as AUC0-24/24 (Cavg) assessment for abediterol on Day 9
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

To assess Cavg after multiple once daily inhaled doses of abediterol 5 μg.

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
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

To assess %Fluctuation after multiple once daily inhaled doses of abediterol 5 μg.

Accumulation ratio for Cmax estimated as (Cmax on Day 9/Cmax on Day 1) (Rac (Cmax)) assessment for abediterol on Day 9
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

To assess Rac (Cmax) after multiple once daily inhaled doses of abediterol 5 μg.

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
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

To assess Rac (AUC0-24) after multiple once daily inhaled doses of abediterol 5 μg.

Vital sign (Blood pressure [BP])
Change from baseline up to Day 13

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.

Vital sign (pulse)
Change from baseline up to Day 13

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.

12-lead Electrocardiograms (ECGs) including high precision QTc analysis and telemetry
Change from baseline up to Day 13

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).

Clinical laboratory assessments (hematology, clinical chemistry and urinalysis)
Change from baseline up to Day 11

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.

Number of patients with Adverse Events (AEs)
Change from baseline up to follow-up (14 ± 2 days post (final) dose)

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.

Area under the plasma concentration time curve (AUC) of abediterol and AZD7594 from time zero extrapolated to infinity. AUC is estimated by AUClast + Clast/λz where Clast is the last observed quantifiable concentration
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Maximum observed plasma concentration (AUClast), taken directly from the individual concentration time curve of abediterol and AZD7594.
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Observed maximum concentration (Cmax) of abediterol and AZD7594, taken directly from the individual concentration time curve.
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz) of abediterol and AZD7594 using plasma concentrations, estimated as (ln2)/λz.
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Time to reach maximum observed plasma concentration (tmax) of abediterol and AZD7594 using plasma concentrations, taken directly from the individual concentration time curve.
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Mean residence time (MRT) of abediterol and AZD7594.
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Apparent estimated as dose divided by AUC.total body clearance of drug from plasma after extravascular administration (CL/F) of abediterol and AZD7594,
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

The time interval (h) of the log linear regression to determine t1/2λz (λz upper and λz lower) of abediterol and AZD7594.
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Terminal elimination rate constant, estimated by log linear least squares regression of the terminal part of the concentration time curve (λz, N) of abediterol and AZD7594.
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Regression coefficient adjusted for λz, N observations, goodness of fit statistic for calculation of λz (Rsq_adj) of abediterol and AZD7594
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Percentage of AUC obtained by extrapolating the area under the plasma concentration time curve from the time of the last quantifiable concentration to infinity (%AUCextr) of abediterol and AZD7594
Day -1 to Day 3. Subjects will also return to the Unit at 72, 96, 144 and 240 hours post-dose (Days 4, 5, 7 and 11 respectively) for PK measurements

Pharmacokinetics of AZD7594 and abediterol following single inhaled doses of AZD7594 alone, abediterol alone and the 2 compounds in FDC or in free combination via 2 separate DPIs

Secondary Endpoints

Safety and tolerability of single inhaled doses of AZD7594 and abediterol alone and in combination assessed by recording the AEs, physical examination, electrocardiogram readings, vital signs, spirometry and clinical laboratory assessments.
From Screening (maximum of 28 days) till Follow up visit (10 to 14 days post final dose), an average of 24 weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Abediterol 5 μgEXPERIMENTALOut of 12 randomized patients, 9 will receive abediterol 5 μg as dry inhalation powder orally once daily for 9 days. Patients will be provided salbutamol as rescue medication for use throughout the study. During the treatment period, all patients will be continued on their current ICSs. In addition, each patient will receive Abediterol 5.0 μg QD.
PlaceboPLACEBO_COMPARATOROut of 12 randomized patients, 3 will receive placebo as dry inhalation powder orally once daily for 9 days. Patients will be provided salbutamol as rescue medication for use throughout the study. During the treatment period, all patients will be continued on their current ICSs. In addition, each patient will receive placebo QD.
Treatment A (Abediterol )EXPERIMENTALTreatment A: The subjects will receive Abediterol 2.5 μg via DPI
Treatment B (AZD7594)EXPERIMENTALTreatment B: The subjects will receive AZD7594 440 μg via DPI
Treatment C (AZD7594/abediterol )EXPERIMENTALTreatment C: The subjects will receive AZD7594/ abediterol 440 μg/2.5 μg FDC via DPI
Treatment D (AZD7594 and abediterol)EXPERIMENTALTreatment D: The subjects will receive AZD7594 440 μg and abediterol 2.5 μg free combination administered via 2 separate DPIs

Interventions

NameTypeDescription
AbediterolDRUGA β2-adrenoceptor agonists, produce smooth muscle relaxation in the airways and improves lung function.
PlaceboDRUGAbediterol matching placebo without any pharmacological activity.
AZD7594DRUGTreatment B: AZD7594 440 μg via DPI
AZD7594/abediterolDRUGTreatment C: AZD7594/abediterol 440 μg/2.5 μg FDC via DPI
AZD7594 and abediterolDRUGTreatment D: AZD7594 440 μg and abediterol 2.5 μg free combination administered via 2 separate DPIs
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Eligibility Criteria

Age Range18 Years to 55 Years
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: * Provision of signed and dated, written informed consent prior to any study specific procedures. * Male and non-pregnant, non-lactating female patients aged 18 - 55 years with asthma and with suitable veins for cannulation or repeated venipuncture. * Non-smoker or former smoker...

Countries:Germany
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Frequently asked questions about Abediterol

What is Abediterol used for?

Abediterol is an investigational small molecule being developed for Chronic Obstructive Pulmonary Disease (COPD) and Asthma. It is administered via inhalation as a dry powder. As of the available data, it is in Phase 1 clinical development and has not been approved by regulatory authorities.

Who makes Abediterol?

Abediterol is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker symbol AZN. The company is conducting clinical trials to evaluate the drug's safety and pharmacokinetics in healthy volunteers and patients with respiratory conditions.

What phase is Abediterol in?

Abediterol is in Phase 1 clinical development. It is an investigational drug, meaning it has not yet received regulatory approval. Clinical trials are ongoing to assess its safety, tolerability, and how the body processes the drug when administered via inhalation.

What clinical trials is Abediterol in?

Abediterol has been studied in two completed Phase 1 clinical trials. NCT02967159 evaluated the disposition and safety of single inhaled doses in healthy male participants. NCT03273127 assessed pharmacokinetics, safety, and tolerability of once-daily dosing for 9 days in patients with asthma on inhaled corticosteroids.

Is Abediterol the same as AZD7594?

No, Abediterol and AZD7594 are different drugs. In clinical trial NCT02967159, they were studied both alone and in combination to evaluate their disposition and safety. The trial used a dry powder inhaler to administer each drug separately, in a fixed dose combination, and in a free combination.