Relative Bioavailability Study With Abediterol Administered Via Three Different Inhalation Devices in Healthy Volunteers.

NCT04199598 | Terminated Phase 1

• 1 other identifier: D6541C00001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The study is intended to assess the relative bioavailability of 2 different abediterol nebulised formulations (test) and the dry powder formulation (reference). The study results will provide information on the pharmacokinetic (PK) profile following use of the 3 devices to be used in further clinical development.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Open-label; Long-acting beta-2 agonist; COPD; Bioavailability; Phase 1; Abediterol; Healthy subjects; Crossover

Outcome Measures

Primary Outcomes (3)

• Geometric mean ratios and 90% confidence intervals for area under plasma (AUC) for test versus abediterol reference treatments

  To estimate the relative bioavailability of abediterol following inhalation via PARI LC SPRINT nebulizer (2 dose levels) or via OMRON NE-C900-E nebulizer (1 dose level) compared to inhalation via DPI SD2FL (1 dose level)

  On Day 1: pre-dose, 5 min [only for DPI], 12, 30, and 45 min, and 1, 2, 4, 6, 8, 12 hours post-dose, on Day 2: 24 and 36 hours post-dose, on Day 3: 48 hours post-dose, on Day 4-7: 72, 96, 120 and 144 hours post-dose.

• Geometric mean ratios and 90% confidence intervals for area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC[0-t]) for test versus reference abediterol treatments

  To estimate the relative bioavailability of abediterol following inhalation via PARI LC SPRINT nebulizer (2 dose levels) or via OMRON NE-C900-E nebulizer (1 dose level) compared to inhalation via DPI SD2FL (1 dose level)

  On Day 1: pre-dose, 5 min [only for DPI], 12, 30, and 45 min, and 1, 2, 4, 6, 8, 12 hours post-dose, on Day 2: 24 and 36 hours post-dose, on Day 3: 48 hours post-dose, on Day 4-7: 72, 96, 120 and 144 hours post-dose.

• Geometric mean ratios and 90% confidence intervals for maximum observed plasma concentration (Cmax) the for test versus reference abediterol treatments

  To estimate the relative bioavailability of abediterol following inhalation via PARI LC SPRINT nebulizer (2 dose levels) or via OMRON NE-C900-E nebulizer (1 dose level) compared to inhalation via DPI SD2FL (1 dose level)

  On Day 1: pre-dose, 5 min [only for DPI], 12, 30, and 45 min, and 1, 2, 4, 6, 8, 12 hours post-dose, on Day 2: 24 and 36 hours post-dose, on Day 3: 48 hours post-dose, on Day 4-7: 72, 96, 120 and 144 hours post-dose.

Secondary Outcomes (49)

• AUC for each abediterol treatment

  On Day 1: pre-dose, 5 min [only for DPI], 12, 30, and 45 min, and 1, 2, 4, 6, 8, 12 hours post-dose, on Day 2: 24 and 36 hours post-dose, on Day 3: 48 hours post-dose, on Day 4-7: 72, 96, 120 and 144 hours post-dose.

• AUC (0-t) for each abediterol treatment

  On Day 1: pre-dose, 5 min [only for DPI], 12, 30, and 45 min, and 1, 2, 4, 6, 8, 12 hours post-dose, on Day 2: 24 and 36 hours post-dose, on Day 3: 48 hours post-dose, on Day 4-7: 72, 96, 120 and 144 hours post-dose.

• Cmax for each abediterol treatment

  On Day 1: pre-dose, 5 min [only for DPI], 12, 30, and 45 min, and 1, 2, 4, 6, 8, 12 hours post-dose, on Day 2: 24 and 36 hours post-dose, on Day 3: 48 hours post-dose, on Day 4-7: 72, 96, 120 and 144 hours post-dose.

• Area under the plasma concentration-time curve from time zero to 24 hours [AUC (0-24)] for each abediterol treatment

  On Day 1: pre-dose, 5 min [only for DPI], 12, 30, and 45 min, and 1, 2, 4, 6, 8, 12 hours post-dose, on Day 2: 24 and 36 hours post-dose, on Day 3: 48 hours post-dose, on Day 4-7: 72, 96, 120 and 144 hours post-dose.

• Maximum concentration (tmax) for each abediterol treatment

  On Day 1: pre-dose, 5 min [only for DPI], 12, 30, and 45 min, and 1, 2, 4, 6, 8, 12 hours post-dose, on Day 2: 24 and 36 hours post-dose, on Day 3: 48 hours post-dose, on Day 4-7: 72, 96, 120 and 144 hours post-dose.

Study Arms (4)

Treatment A (test product): Abediterol (2.4 μg)

EXPERIMENTAL

Randomized subjects will receive single dose treatment of Abediterol nebuliser solution for inhalation via PARI LC SPRINT nebulizer following an overnight fast of at least 8 hours

Drug: Abediterol (2.4 μg)

Treatment B (Test Product): Abediterol (4.8 μg)

EXPERIMENTAL

Randomized subjects will receive single dose treatment of Abediterol nebuliser solution for inhalation via PARI LC SPRINT nebulizer following an overnight fast of at least 8 hours

Drug: Abediterol (4.8 μg)

Treatment C(Test Product):Abediterol(2.4 μg)

EXPERIMENTAL

Randomized subjects will receive single dose treatment of Abediterol nebuliser solution for inhalation via OMRON NE-C900-E nebulizer following an overnight fast of at least 8 hours

Drug: Abediterol (2.4 μg)

Treatment D (Reference Product): Abediterol (2.5 μg)

EXPERIMENTAL

Randomized subjects will receive single dose treatment of Abediterol (as napadisylate) inhalation powder via dry powder inhaler (DPI) following an overnight fast of at least 8 hours

Drug: Abediterol (2.5 μg)

Interventions

Abediterol (2.4 μg) DRUG

2.4 μg (delivered dose) abediterol via PARI LC SPRINT nebuliser

Treatment A (test product): Abediterol (2.4 μg)

Abediterol (4.8 μg) DRUG

4.8 μg (delivered dose) abediterol via PARI LC SPRINT nebuliser

Treatment B (Test Product): Abediterol (4.8 μg)

Abediterol (2.5 μg) DRUG

2.5 μg (nominal dose) abediterol via DPI, reference

Treatment D (Reference Product): Abediterol (2.5 μg)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study-specific procedures.
• Healthy male subjects aged 18 - 45 years, inclusive, with suitable veins for cannulation or repeated venipuncture.
• Have a body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• Subject is able to understand and communicate in German.
• Willing and able to comply with all required study procedures.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
• History or presence of gastrointestinal (GI), hepatic or renal disease, or any other conditions (e.g., including Gilbert's syndrome, gallstone and cholecystectomy) known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• History of tuberculosis, any other significant lung diseases like surgeries, asthma, COPD.
• Upper respiratory tract infections within 14 days of the first study day, or lower respiratory tract infection within 3 months prior to screening.
• Any clinically significant illness, medical/surgical procedure, or trauma within
• weeks of the first administration of IMP. 6 Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at screening and first admission to the study unit (first treatment period) as judged by the PI. 7 Any clinically significant abnormal findings in vital signs at screening and first admission to the study unit (first treatment period), as judged by the PI, and defined as:
• Systolic BP \<90 mmHg or ≥140 mmHg and diastolic BP \<50 mmHg or
• ≥90 mmHg
• Heart rate \<50 beats per minute \[bpm\] or \>90 bpm Note: Assessments may be repeated once to confirm values. 8 Any clinically significant abnormalities on 12-lead ECG at screening and first admission to the study unit (first treatment period), as judged by the PI, and defined as:
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI or positive screen for drugs of abuse, cotinine, and/or alcohol at screening or on each admission to the Clinical Unit. 17 Subjects with a pregnant partner. 18 Involvement of any AstraZeneca, Parexel or study site employee or their close relatives. 19 Subjects who have previously received abediterol. 20 Judgement by the PI that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements. 21 Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

5-(2-((6-(2,2-difluoro-2-phenylethoxy)hexyl)amino)-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dr. med. Rainard Fuhr

  Parexel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: December 16, 2019
• Study Start: January 28, 2020
• Primary Completion: April 3, 2020
• Study Completion: April 3, 2020
• Last Updated: April 21, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

DE (1)