Chronic Obstructive Pulmonary DiseasePhase 1NCT04199598
Relative Bioavailability Study With Abediterol Administered Via Three Different Inhalation Devices in Healthy Volunteers.
A Phase 1 study testing Abediterol (2.4 μg), Abediterol (4.8 μg) and Abediterol (2.5 μg) in people with Chronic Obstructive Pulmonary Disease, run by AstraZeneca at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Abediterol (2.4 μg), Abediterol (4.8 μg) and Abediterol (2.5 μg)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteGermany
- Study dates
- 28 Jan 2020to 3 Apr 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
- 4 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:
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- 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:
- Sick sinus syndrome (2) Arrhythmia (3) Prolonged QT interval corrected using Fridericia's formula (QTcF) > 450 ms (4) Family history of long QT syndrome, persistent or intermittent bundle branch block (BBB), AV block grade II or III 9 Any positive result on screening for serum hepatitis B surface antigen (HBsAg) OR anti-hepatitis B core antigen (HBc) antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody. 10 Has received another new chemical and biologic entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or one month after the last visit whichever is the longest. Note: subjects consented and screened, but not randomized in this study or a previous phase I study, are not excluded. 11 Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening. 12 History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to abediterol. 13 Current smokers or those who have smoked or used nicotine products (including e- cigarettes; > 10 pack-year) within the 3 months prior to screening. 14 Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP. 15 Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
- 16 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Single-center, Randomized, 4-period, Single Dose, Crossover Study to Assess the Relative Bioavailability of Abediterol Inhaled Via Two Different Nebulizers and Via Dry Powder Inhaler in Healthy Subjects.
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.
Read the detailed description
This study will be an open-label, randomized, 4-period, single-dose, single-center, crossover study with a William's design in healthy subjects (males).
The study will comprise:
- A screening period of maximum 28 days;
- Four treatment periods during which subjects will be resident prior to the evening meal the night before dosing with abediterol (Day -1) until at least 48 hours following dosing for collection of PK samples; discharged on the morning of Day 3; and
- A final safety post-treatment visit within 14 days after the last administration of abediterol.
There will be a minimum washout period of 14 days between each treatment period.
Each subject will be involved in the study for approximately 12 weeks.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Abediterol (2.4 μg), Abediterol (4.8 μg), Abediterol (2.5 μg)
- Keywords
- Open-label, Long-acting beta-2 agonist, COPD, Bioavailability, Phase 1, Abediterol, Healthy subjects, Crossover
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abediterol (2.4 μg)Drug
2.4 μg (delivered dose) abediterol via PARI LC SPRINT nebuliser
Abediterol (4.8 μg)Drug
4.8 μg (delivered dose) abediterol via PARI LC SPRINT nebuliser
Abediterol (2.4 μg)Drug
2.4 μg (delivered dose) abediterol via OMRON NE-C900-E nebuliser
Abediterol (2.5 μg)Drug
2.5 μg (nominal dose) abediterol via DPI, reference
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Abediterol (2.5 μg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: 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
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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.
Terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz) for each abediterol treatment
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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.
Terminal elimination rate constant (λz) for each abediterol treatment
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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.
Time of last quantifiable plasma concentration (tlast) for each abediterol treatment
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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.
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for each abediterol treatment
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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.
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for each abediterol treatment
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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.
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) for each abediterol treatment
To evaluate the PK profile of abediterol when administered via the 3 devices (DPI and 2 nebulisers)
Measured: 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.
Number of subjects with adverse events
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal electrocardiogram (ECG)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28), Day -1 until Day 3
Number of subjects with abnormal telemetry
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: Day -1, 1 (pre-dose to 12 hours from the start of study drug administration)
Number of subjects with abnormal vital signs
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until Day 3
Number of subjects with abnormal physical examination
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal spirometry
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: At Screening (Day -28) and Day 1
Number of subjects with abnormal taste questionnaire
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: Day 1
Number of subjects with abnormal White blood cell (WBC) count
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Red blood cell (RBC) count
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Hemoglobin (Hb)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Hematocrit (HCT)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Mean corpuscular volume (MCV)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Mean corpuscular hemoglobin (MCH)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Mean corpuscular hemoglobin concentration (MCHC)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Neutrophils absolute count
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Lymphocytes absolute count
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Monocytes absolute count
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Eosinophils absolute count
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Basophils absolute count
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Reticulocytes absolute count
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal sodium
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal pottasium
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal urea
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal creatinine
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal albumin
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal calcium
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal phosphate
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal glucose (fasting)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal C-reactive protein (CRP)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Alkaline phosphatase (ALP)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Alanine aminotransferase (ALT)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Aspartate aminotransferase (AST)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Total Bilirubin
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Unconjugated bilirubin
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: Screening (Day -28), Day -1, 1 and 14 days after last dose
Number of subjects with abnormal Thyroid-stimulating hormone (TSH)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: Screening (Day -28)
Number of subjects with abnormal urinalysis (glucose, blood and protein)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: Screening (Day -28) and Day -1
Number of subjects with abnormal Gamma glutamyl transpeptidase (GGT)
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal platelet
To further assess the safety of single doses administration of abediterol in healthy subjects
Measured: From Screening (Day -28) until follow-up (14 days after last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start28 Jan 2020
- Primary completion3 Apr 2020
- Study completion3 Apr 2020
Why it stopped: The decision to terminate has been taken by the Sponsor. The decision is not due to safety concerns but reflects business prioritizations of the company.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Dr. med. Rainard Fuhr, Principal investigator, Parexel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04199598
- Sponsor's protocol ID
- D6541C00001
- Status last verified
- Apr 2020
- First submitted
- 12 Dec 2019
- Last updated
- 21 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-center, Randomized, 4-period, Single Dose, Crossover Study to Assess the Relative Bioavailability of Abediterol Inhaled Via Two Different Nebulizers and Via Dry Powder Inhaler in Healthy Subjects.
- ClinicalTrials.gov ID
- NCT04199598
- Acronym / sponsor ID
- D6541C00001
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- Open-label, Long-acting beta-2 agonist, COPD, Bioavailability, Phase 1, Abediterol, Healthy subjects, Crossover
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The decision to terminate has been taken by the Sponsor. The decision is not due to safety concerns but reflects business prioritizations of the company.
- Enrolment
- 25 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 28 Jan 2020 (actual)
- Primary completion
- 3 Apr 2020 (actual)
- Study completion
- 3 Apr 2020 (actual)
- First posted
- 16 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will be an open-label, randomized, 4-period, single-dose, single-center, crossover study with a William's design in healthy subjects (males).
The study will comprise:
- A screening period of maximum 28 days;
- Four treatment periods during which subjects will be resident prior to the evening meal the night before dosing with abediterol (Day -1) until at least 48 hours following dosing for collection of PK samples; discharged on the morning of Day 3; and
- A final safety post-treatment visit within 14 days after the last administration of abediterol.
There will be a minimum washout period of 14 days between each treatment period.
Each subject will be involved in the study for approximately 12 weeks.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment A (test product): Abediterol (2.4 μg) | Experimental | Drug: Abediterol (2.4 μg)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 |
| Treatment B (Test Product): Abediterol (4.8 μg) | Experimental | Drug: Abediterol (4.8 μg)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 |
| Treatment C(Test Product):Abediterol(2.4 μg) | Experimental | Drug: Abediterol (2.4 μg)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 |
| Treatment D (Reference Product): Abediterol (2.5 μg) | Experimental | Drug: Abediterol (2.5 μg)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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abediterol (2.4 μg)2.4 μg (delivered dose) abediterol via PARI LC SPRINT nebuliser | Drug | Treatment A (test product): Abediterol (2.4 μg) |
| Abediterol (4.8 μg)4.8 μg (delivered dose) abediterol via PARI LC SPRINT nebuliser | Drug | Treatment B (Test Product): Abediterol (4.8 μg) |
| Abediterol (2.4 μg)2.4 μg (delivered dose) abediterol via OMRON NE-C900-E nebuliser | Drug | Treatment C(Test Product):Abediterol(2.4 μg) |
| Abediterol (2.5 μg)2.5 μg (nominal dose) abediterol via DPI, reference | Drug | Treatment D (Reference Product): Abediterol (2.5 μg) |
Primary outcome
Geometric mean ratios and 90% confidence intervals for area under plasma (AUC) for test versus abediterol reference treatments
Time frame: 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.
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)
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
Time frame: 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.
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)
Geometric mean ratios and 90% confidence intervals for maximum observed plasma concentration (Cmax) the for test versus reference abediterol treatments
Time frame: 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.
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)
49 secondary outcomes
AUC for each abediterol treatment
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz) for each abediterol treatment
Time frame: 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.
Terminal elimination rate constant (λz) for each abediterol treatment
Time frame: 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.
Time of last quantifiable plasma concentration (tlast) for each abediterol treatment
Time frame: 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.
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for each abediterol treatment
Time frame: 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.
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for each abediterol treatment
Time frame: 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.
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) for each abediterol treatment
Time frame: 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.
Number of subjects with adverse events
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal electrocardiogram (ECG)
Time frame: From Screening (Day -28), Day -1 until Day 3
Number of subjects with abnormal telemetry
Time frame: Day -1, 1 (pre-dose to 12 hours from the start of study drug administration)
Number of subjects with abnormal vital signs
Time frame: From Screening (Day -28) until Day 3
Number of subjects with abnormal physical examination
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal spirometry
Time frame: At Screening (Day -28) and Day 1
Number of subjects with abnormal taste questionnaire
Time frame: Day 1
Number of subjects with abnormal White blood cell (WBC) count
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Red blood cell (RBC) count
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Hemoglobin (Hb)
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Hematocrit (HCT)
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Mean corpuscular volume (MCV)
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Mean corpuscular hemoglobin (MCH)
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Mean corpuscular hemoglobin concentration (MCHC)
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Neutrophils absolute count
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Lymphocytes absolute count
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Monocytes absolute count
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Eosinophils absolute count
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Basophils absolute count
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal Reticulocytes absolute count
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal sodium
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal pottasium
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal urea
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal creatinine
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal albumin
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal calcium
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal phosphate
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal glucose (fasting)
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Number of subjects with abnormal C-reactive protein (CRP)
Time frame: From Screening (Day -28) until follow-up (14 days after last dose)
Results and safety
The study was stopped early (reason given: The decision to terminate has been taken by the Sponsor. The decision is not due to safety concerns but reflects business prioritizations of the company.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2020.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. med. Rainard Fuhr principal investigator
Parexel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Abediterol (2.4 μg), Abediterol (4.8 μg) and Abediterol (2.5 μg) in people with Chronic Obstructive Pulmonary Disease, run by AstraZeneca at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The decision to terminate has been taken by the Sponsor. The decision is not due to safety concerns but reflects business prioritizations of the company.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Geometric mean ratios and 90% confidence intervals for area under plasma (AUC) for test versus abediterol reference treatments (time frame: 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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2020.