A Single Dose PD & PK Study With Two Formulations of Abediterol in Patients With Asthma

NCT02777827 | Completed Phase 1 Results

• 1 other identifier: D6540C00002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief 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 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.

Conditions

Asthma

Keywords

Abediterol; Dry powder inhaler; Pressured metered-dose inhaler; Pharmacokinetic; Pharmacodynamic; Safety

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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

  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)

  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).

  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)

  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.

Study Arms (6)

Abediterol dry powder inhaler 0.156 μg

EXPERIMENTAL

Dry powder for inhalation administered via dry powder inhaler 0.156 μg/inhalation; (1 inhalation)

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).

Drug: Abediterol 2.5 μg

Abediterol pressurised metered-dose inhaler 0.05μg

EXPERIMENTAL

Pressurised metered-dose, inhaler 0.025 μg/puff; (2 puffs).

Drug: Abediterol 0.05 μg

Abediterol pressurised metered-dose inhaler 0.156 μg

EXPERIMENTAL

Pressurised metered-dose, inhaler 0.078 μg/puff; (2 puffs).

Drug: Abediterol 0.156 μg

Abediterol pressurised metered-dose inhaler 2.5μg

EXPERIMENTAL

Pressurised metered-dose inhaler 1.25 μg/puff; (2 puffs).

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).

Other: Placebo

Interventions

Abediterol 0.156 μg DRUG

Dry powder for inhalation

Abediterol dry powder inhaler 0.156 μg

Abediterol 2.5 μg DRUG

Dry powder for inhalation

Abediterol dry powder inhaler 2.5 μg

Abediterol 0.05 μg DRUG

Pressurised metered-dose inhaler

Abediterol pressurised metered-dose inhaler 0.05μg

Placebo OTHER

Pressurised metered-dose inhaler and dry powder for inhalation.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Berlin, 14050, Germany

Location

Research Site

Großhansdorf, 22927, Germany

Location

Research Site

Lübeck, 23552, Germany

Location

Research Site

Wiesbaden, 65187, Germany

Location

MeSH Terms

Conditions

Asthma

Interventions

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

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Jutta Beier, Dr

  Biebricher Allee 34, Wiesbaden, Germany, 65187.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2016
• First Posted: May 19, 2016
• Study Start: June 21, 2016
• Primary Completion: November 29, 2016
• Study Completion: November 29, 2016
• Last Updated: January 24, 2019
• Results First Posted: January 24, 2019

Record last verified: 2019-01

Locations

DE (4)