AsthmaPhase 1NCT02777827
A Single Dose PD & PK Study With Two Formulations of Abediterol in Patients With Asthma
A Phase 1 study testing Abediterol 0.156 μg, Abediterol 2.5 μg and Abediterol 0.05 μg in people with Asthma, run by AstraZeneca at 4 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Asthma
- What is being tested?
- Abediterol 0.156 μg, Abediterol 2.5 μg and Abediterol 0.05 μg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 4 sitesGermany
- Study dates
- 21 Jun 2016to 29 Nov 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent before any study specific procedures.
- Men or non-pregnant, non-lactating women 18 to 75 years of age, inclusive.
- Non-smoker or ex-smoker (quit ≥6months prior to Visit 1) with a total smoking history of ≤10 pack years.
- Documented clinical diagnosis of asthma for ≥6 months before Visit 1 according to GINA guidelines.
- 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.
- Prebronchodilator FEV1 at Visit 2 ≥40% and ≤85% of predicted (1 repetition of the test is allowed before screen failure).
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- 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).
- Demonstrate the ability to use the study inhalation device properly.
- Able to perform repeated pulmonary function testing for FEV1.
- Able to read, speak and understand German.
- Patient must agree to all restrictions during the study.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Participation in another clinical study with an IP during the last 3 months.
- Known or suspected hypersensitivity to the IP or excipients, including lactose (Note: lactose intolerance is not an exclusion).
- Systemic steroid use in the 6 weeks before Visit 1.
- Hospitalization due to asthma in the 6 months prior to Visit 1.
- Any active pulmonary disease other than asthma.
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- Non-compliance with study procedures in the run in period - as judged by the Investigator.
- 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).
- Treatment with any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to Visit 1.
- Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to Visit 1.
- 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.
- Known chronic hepatitis or HIV infections at the time of enrolment.
- Any active malignancy or treatment thereof within the 3 years prior to enrolment.
- Any clinically important abnormalities in rhythm, conduction, or morphology of the screening 12-lead ECG as judged by the Investigator on the screening ECG.
- 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.
- PR (PQ) interval prolongation (> 240 msec), intermittent second or third degree atrialventricular (AV) block or AV dissociation on the screening ECG.
- Implantable cardiac defibrillator and patients with sustained symptomatic ventricular and/or atrial tachyarrhythmia.
- Any contraindication against the use of sympathomimetic drugs as judged by the Investigator.
- 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.
- History of hospitalisation within 12 months caused by heart failure or a diagnosis of heart failure higher than New York Heart Association Class II.
- Suspected poor capability to follow instructions of the study, as judged by the Investigator.
- History of or current alcohol or drug abuse (including marijuana), as judged by the Investigator.
- Planned in-patient surgery, major dental procedure or hospitalisation during the study.
- 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).
- 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.
Trial locations and contacts
4 sites in 1 country.
Germany4 sites
Research Site
Berlin, 14050
Research Site
Großhansdorf, 22927
Research Site
Lübeck, 23552
Research Site
Wiesbaden, 65187
About this study
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.
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.
Read the detailed 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.
- Conditions
- Asthma
- Being tested
- Abediterol 0.156 μg, Abediterol 2.5 μg, Abediterol 0.05 μg, Placebo
- Keywords
- Abediterol, Dry powder inhaler, Pressured metered-dose inhaler, Pharmacokinetic, Pharmacodynamic, Safety
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abediterol 0.156 μgDrug
Dry powder for inhalation
Abediterol 2.5 μgDrug
Dry powder for inhalation
Abediterol 0.05 μgDrug
Pressurised metered-dose inhaler
Abediterol 0.156 μgDrug
Pressurised metered-dose inhaler
Abediterol 2.5 μgDrug
Pressurised metered-dose inhaler
PlaceboOther
Pressurised metered-dose inhaler and dry powder for inhalation.
| Study group | Role | What they receive |
|---|---|---|
| Abediterol dry powder inhaler 0.156 μg | Experimental | Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation) Receives: Drug: Abediterol 0.156 μg |
| Abediterol dry powder inhaler 2.5 μg | Experimental | Dry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation). Receives: Drug: Abediterol 2.5 μg |
| Abediterol pressurised metered-dose inhaler 0.05μg | Experimental | Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs). Receives: Drug: Abediterol 0.05 μg |
| Abediterol pressurised metered-dose inhaler 0.156 μg | Experimental | Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs). Receives: Drug: Abediterol 0.156 μg |
| Abediterol pressurised metered-dose inhaler 2.5μg | Experimental | Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs). Receives: Drug: Abediterol 2.5 μg |
| Placebo | Placebo comparator | Pressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1).
Baseline for FEV1 was defined as the mean of the two measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min), prior to the morning investigational product (IP) administration on Day 1 of each treatment period. If both were missing the screening value was used instead.
Trough is defined as the mean of the FEV1 values obtained at 23 h and 24 h after the morning IP administration. If one of the values was missing, the other one was used as trough.
Measured: 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1
Secondary outcomes (23)
Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1.
The percentage of patients achieving at least 200 mL and 12% increase from baseline in peak FEV1 on Day 1 of each treatment. The peak was the highest value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Measured: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Time to Peak FEV1 at Day 1
The peak is the highest forced expiratory volume in one second (FEV1) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Measured: 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Observed Maximum Concentration of Abediterol (Cmax)
Observed maximum concentration (Cmax) of Abediterol, taken directly from the individual concentration-time curve.
Measured: 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 (h) to Maximum Concentration of Abediterol (Tmax).
Time to maximum concentration (Tmax) of Abediterol (h), taken directly from the individual concentration-time curve.
Measured: 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 of Abediterol (λz)
Terminal rate constant (λz) of Abediterol, estimated by log-linear least square regression of the terminal part of the concentration-time curve.
Measured: 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) of Abediterol (t½λz)
Terminal half-life (h), estimated as (ln2)/λz (t1/2λz).
Measured: 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.
AUClast of Abediterol
Area under the plasma concentration-curve of Abediterol from time zero to the time of last quantifiable analyte concentration.
Measured: 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.
AUC of Abediterol.
Area under the Abediterol concentration-time curve from time zero extrapolated to infinity (AUC). AUC is estimated by AUClast + Clast/λz where Clast is the last observed quantifiable concentration (AUC).
PK blood samples were collected 5, 15, 30, and 45 minutes, at 1, 2.5, 4, 6, 8, 12, 24 and 36 hours after IP administration on Day 1 (Note that 24 h and 36 h time-points post-dose correspond to Day 2).
Measured: 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 Abediterol (CL/F).
Apparent plasma clearance for parent drug estimated as dose divided by AUC (CL/F).
Measured: 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 Abediterol at Terminal Phase (Vz/F).
Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz (Vz/F).
Measured: 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 (MRT) of Abediterol.
Mean residence time (h), calculated by AUMC/AUC, where AUMC is the area under the first moment-time curve (MRT).
Measured: 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.
Number of Participants With Any Treatment-emergent Adverse Event
All treatment emergent adverse events (TEAEs), including serious AEs. An AE is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An AE was considered a TEAE if it was not present prior to the date of the first dose of IP or was present prior to the date of the first dose of IP, but increased in severity after IP administration.
Measured: From screening (Day -14) up to follow-up phone call (14 days after last IP administration).
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
Standard 12-lead ECG evaluations were performed prior to IP administration and 1, 4 and 24 h post IP administration at randomisation and after each IP administration. ECGs were recorded after approximately 5 minutes resting in supine position before any blood sampling and spirometry test, preferably always by the same technician for each patient.
Clinically significant abnormalities were defined as listed in the table below for QT interval, QTcB, QTcF, QRS interval, PR interval and heart rate (HR).
BL incr. = increase from baseline.
Measured: Up to last treatment visit (Day 112)
Time to Peak FVC at Day 1
The peak is the highest forced vital capacity (FVC) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Measured: 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1.
The percentage of patients achieving at least 200 mL and 12% increase from baseline in trough forced expiratory volume in one second (FEV1). Trough was defined as the mean of the FEV1 values obtained at 23 hours and 24 hours after the morning IP administration.
Measured: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Change From Baseline in Peak FEV1.
The peak is the highest forced expiratory volume in one second (FEV1) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Measured: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Change From Baseline in Normalised FEV1 AUC0-24.
Change from baseline in normalised FEV1 area under the concentration-curve of Abediterol from time zero to 24 hours post-dose.
Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead.
Measured: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1
Change From Baseline in Normalised FEV1 AUC0-12.
Change from baseline in normalised FEV1 area under the concentration time curve for Abediterol from time zero to 12 hours post-dose.
Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead.
Measured: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, and 12 h post-dose on Day 1
Change From Baseline in Normalised FEV1 AUC0-6.
Change from baseline in normalised FEV1 area under the concentration-curve for Abediterol from time zero to 6 hours post-dose.
Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead.
Measured: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, and 6 h post dose on Day 1
Change From Baseline in Normalised FEV1 AUC12-24.
Change from baseline in normalised FEV1 area under the concentration-curve for Abediterol from time 12 hours post-dose to 24 hours post-dose.
Baseline for FEV1 was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead.
Measured: 45 mins and 15 mins predose, and 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1
Change From Baseline in Peak FVC.
Baseline for FVC was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FEV1 from Visit 2) was used instead.
The peak is the highest forced vital capacity (FVC) value observed during the 6 hour-period immediately after the IP dose in the morning on Day 1.
Measured: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Change From Baseline in Trough FVC.
Baseline for FVC was defined as the mean of the two measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min), prior to the morning investigational product (IP)administration on Day 1 of each treatment period. If both were missing the screening value was used instead.
Trough was defined as the mean of the FEV1 values obtained at 23 h and 24 h after the morning IP administration. If one of the values was missing, the other one was used as trough.
Measured: 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1
Change From Baseline in Normalised FVC AUC0-24.
Change from baseline in normalised FVC area under the concentration curve for Abediterol from time zero to 24 hours post-dose.
Baseline for FVC was defined as the mean of the 2 measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min before the morning IP administration). If both values were missing, the screening value (pre-bronchodilator FVC from Visit 2) was used instead.
Measured: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2016 (estimated)
- Study start21 Jun 2016
- Primary completion29 Nov 2016
- Study completion29 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AsthmaStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jutta Beier, Dr, Principal investigator, Biebricher Allee 34, Wiesbaden, Germany, 65187.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02777827
- Sponsor's protocol ID
- D6540C00002
- Status last verified
- Jan 2019
- First submitted
- 29 Apr 2016
- Last updated
- 24 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02777827
- Acronym / sponsor ID
- D6540C00002
- Conditions
- Asthma
- Keywords
- Abediterol, Dry powder inhaler, Pressured metered-dose inhaler, Pharmacokinetic, Pharmacodynamic, Safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 21 Jun 2016 (actual)
- Primary completion
- 29 Nov 2016 (actual)
- Study completion
- 29 Nov 2016 (actual)
- First posted
- 19 May 2016 (estimated)
- Results
- Posted 24 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Abediterol dry powder inhaler 0.156 μg | Experimental | Drug: Abediterol 0.156 μgDry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation) |
| Abediterol dry powder inhaler 2.5 μg | Experimental | Drug: Abediterol 2.5 μgDry powder for inhalation, administered via dry powder, inhaler 2.5 μg/inhalation; (1 inhalation). |
| Abediterol pressurised metered-dose inhaler 0.05μg | Experimental | Drug: Abediterol 0.05 μgPressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs). |
| Abediterol pressurised metered-dose inhaler 0.156 μg | Experimental | Drug: Abediterol 0.156 μgPressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs). |
| Abediterol pressurised metered-dose inhaler 2.5μg | Experimental | Drug: Abediterol 2.5 μgPressurised metered-dose inhaler 1.25 μg/puff; (2 puffs). |
| Placebo | Placebo comparator | Other: PlaceboPressurised metered-dose inhaler (2 puffs) and Dry powder for inhalation administered via dry powder inhaler (1 inhalation). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Provision of informed consent before any study specific procedures.
- Men or non-pregnant, non-lactating women 18 to 75 years of age, inclusive.
- Non-smoker or ex-smoker (quit ≥6months prior to Visit 1) with a total smoking history of ≤10 pack years.
- Documented clinical diagnosis of asthma for ≥6 months before Visit 1 according to GINA guidelines.
- 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.
Key exclusion criteria (28 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Participation in another clinical study with an IP during the last 3 months.
- Known or suspected hypersensitivity to the IP or excipients, including lactose (Note: lactose intolerance is not an exclusion).
- Systemic steroid use in the 6 weeks before Visit 1.
- Hospitalization due to asthma in the 6 months prior to Visit 1.
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 0.156 μgDry powder for inhalation | Drug | Abediterol dry powder inhaler 0.156 μg |
| Abediterol 2.5 μgDry powder for inhalation | Drug | Abediterol dry powder inhaler 2.5 μg |
| Abediterol 0.05 μgPressurised metered-dose inhaler | Drug | Abediterol pressurised metered-dose inhaler 0.05μg |
| Abediterol 0.156 μgPressurised metered-dose inhaler | Drug | Abediterol pressurised metered-dose inhaler 0.156 μg |
| Abediterol 2.5 μgPressurised metered-dose inhaler | Drug | Abediterol pressurised metered-dose inhaler 2.5μg |
| PlaceboPressurised metered-dose inhaler and dry powder for inhalation. | Other | Placebo |
Primary outcome
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1).
Time frame: 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1
Baseline for FEV1 was defined as the mean of the two measured values for the corresponding variable (2 measurements 30 min apart, at -45 min and -15 min), prior to the morning investigational product (IP) administration on Day 1 of each treatment period. If both were missing the screening value was used instead. Trough is defined as the mean of the FEV1 values obtained at 23 h and 24 h after the morning IP administration. If one of the values was missing, the other one was used as trough.
23 secondary outcomes
Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1.
Time frame: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Time to Peak FEV1 at Day 1
Time frame: 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Observed Maximum Concentration of Abediterol (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 (h) to Maximum Concentration of Abediterol (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 of Abediterol (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) of Abediterol (t½λz)
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.
AUClast of Abediterol
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.
AUC of Abediterol.
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 Abediterol (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 Abediterol at Terminal Phase (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 (MRT) of Abediterol.
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.
Number of Participants With Any Treatment-emergent Adverse Event
Time frame: From screening (Day -14) up to follow-up phone call (14 days after last IP administration).
Number of Participants With Post-baseline Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters
Time frame: Up to last treatment visit (Day 112)
Time to Peak FVC at Day 1
Time frame: 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Trough FEV1.
Time frame: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Change From Baseline in Peak FEV1.
Time frame: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Change From Baseline in Normalised FEV1 AUC0-24.
Time frame: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1
Change From Baseline in Normalised FEV1 AUC0-12.
Time frame: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, and 12 h post-dose on Day 1
Change From Baseline in Normalised FEV1 AUC0-6.
Time frame: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, and 6 h post dose on Day 1
Change From Baseline in Normalised FEV1 AUC12-24.
Time frame: 45 mins and 15 mins predose, and 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1
Change From Baseline in Peak FVC.
Time frame: Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on Day 1
Change From Baseline in Trough FVC.
Time frame: 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1
Change From Baseline in Normalised FVC AUC0-24.
Time frame: 45 mins and 15 mins predose, and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h, 6 h, 12 h, 16 h, 22 h, and 23.00-24.00 h post-dose on Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jutta Beier, Dr principal investigator
Biebricher Allee 34, Wiesbaden, Germany, 65187.
4 sites 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 0.156 μg, Abediterol 2.5 μg and Abediterol 0.05 μg in people with Asthma, run by AstraZeneca at 4 sites 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 11 inclusion and 28 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: finished, as of the sponsor's last update on 24 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 24 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1). (time frame: 45 mins and 15 mins pre-dose, and 23.00-24.00 h post-dose on Day 1). 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 24 Jan 2019.