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NCT02777827

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

Completed Phase 1 Results posted Last updated 24 January 2019
What this trial tests

Phase 1 trial testing Abediterol 0.156 μg in Asthma in 30 participants. Completed in 29 November 2016.

Timeline
21 June 2016
Primary endpoint
29 November 2016
29 November 2016

Quick facts

Lead sponsorAstraZeneca
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingdouble
Primary purposetreatment
Enrollment30
Start date21 June 2016
Primary completion29 November 2016
Estimated completion29 November 2016
Sites4 locations across Germany

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 75, any sex, with Asthma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1). Primary · 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.

GroupValue95% CI
Abediterol Dry Powder Inhaler 0.156 μg0.225± 0.192
Abediterol Dry Powder Inhaler 2.5 μg0.400± 0.269
Abediterol Pressurised Metered-dose Inhaler 0.05μg0.108± 0.212
Abediterol Pressurised Metered-dose Inhaler 0.156 μg0.170± 0.207
Abediterol Pressurised Metered-dose Inhaler 2.5μg0.407± 0.240
Placebo-0.001± 0.244
Percentage of Participants Achieving a ≥ 200 mL and ≥12% Increase From Baseline in Peak FEV1 on Day 1. Secondary · Predose and 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose 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.

GroupValue95% CI
Abediterol Dry Powder Inhaler 0.156 μg72.41
Abediterol Dry Powder Inhaler 2.5 μg82.76
Abediterol Pressurised Metered-dose Inhaler 0.05μg56.67
Abediterol Pressurised Metered-dose Inhaler 0.156 μg73.33
Abediterol Pressurised Metered-dose Inhaler 2.5μg90.00
Placebo24.14
Time to Peak FEV1 at Day 1 Secondary · 5 mins, 15 mins, 30 mins, 1 h, 2 h, 4 h and 6 h post-dose on 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.

GroupValue95% CI
Abediterol Dry Powder Inhaler 0.156 μg3.7± 1.8
Abediterol Dry Powder Inhaler 2.5 μg3.3± 1.8
Abediterol Pressurised Metered-dose Inhaler 0.05μg3.0± 1.9
Abediterol Pressurised Metered-dose Inhaler 0.156 μg3.5± 1.7
Abediterol Pressurised Metered-dose Inhaler 2.5μg3.6± 2.0
Placebo2.9± 2.2
Observed Maximum Concentration of Abediterol (Cmax) Secondary · 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.

Observed maximum concentration (Cmax) of Abediterol, taken directly from the individual concentration-time curve.

GroupValue95% CI
Abediterol Dry Powder Inhaler 0.156 μg0.2299± 117.3
Abediterol Dry Powder Inhaler 2.5 μg1.092± 47.34
Abediterol Pressurised Metered-dose Inhaler 0.156 μg0.2460± 128.7
Abediterol Pressurised Metered-dose Inhaler 2.5μg1.211± 82.21
Time (h) to Maximum Concentration of Abediterol (Tmax). Secondary · 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 to maximum concentration (Tmax) of Abediterol (h), taken directly from the individual concentration-time curve.

GroupValue95% CI
Abediterol Dry Powder Inhaler 0.156 μg0.9800.230 – 1.00
Abediterol Dry Powder Inhaler 2.5 μg0.5000.230 – 1.00
Abediterol Pressurised Metered-dose Inhaler 0.156 μg0.7350.480 – 35.6
Abediterol Pressurised Metered-dose Inhaler 2.5μg0.6200.070 – 12.0
Terminal Rate Constant of Abediterol (λz) Secondary · 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 (λz) of Abediterol, estimated by log-linear least square regression of the terminal part of the concentration-time curve.

GroupValue95% CI
Abediterol Dry Powder Inhaler 2.5 μg0.0526± 0.0228
Abediterol Pressurised Metered-dose Inhaler 2.5μg0.0640± 0.0201
Terminal Half-life (h) of Abediterol (t½λz) Secondary · 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), estimated as (ln2)/λz (t1/2λz).

GroupValue95% CI
Abediterol Dry Powder Inhaler 2.5 μg14.99± 4.827
Abediterol Pressurised Metered-dose Inhaler 2.5μg11.85± 3.533
AUClast of Abediterol Secondary · 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.

Area under the plasma concentration-curve of Abediterol from time zero to the time of last quantifiable analyte concentration.

GroupValue95% CI
Abediterol Dry Powder Inhaler 2.5 μg9.092± 53.95
Abediterol Pressurised Metered-dose Inhaler 2.5μg7.674± 132.5
AUC of Abediterol. Secondary · 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.

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).

GroupValue95% CI
Abediterol Dry Powder Inhaler 2.5 μg12.73± 43.26
Abediterol Pressurised Metered-dose Inhaler 2.5μg11.08± 50.01
Apparent Plasma Clearance for Abediterol (CL/F). Secondary · 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 parent drug estimated as dose divided by AUC (CL/F).

GroupValue95% CI
Abediterol Dry Powder Inhaler 2.5 μg196.4± 43.26
Abediterol Pressurised Metered-dose Inhaler 2.5μg225.6± 50.01
Apparent Volume of Distribution for Abediterol at Terminal Phase (Vz/F). Secondary · 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 parent drug at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz (Vz/F).

GroupValue95% CI
Abediterol Dry Powder Inhaler 2.5 μg4008± 37.41
Abediterol Pressurised Metered-dose Inhaler 2.5μg3690± 49.93
Mean Residence Time (MRT) of Abediterol. Secondary · 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 (h), calculated by AUMC/AUC, where AUMC is the area under the first moment-time curve (MRT).

GroupValue95% CI
Abediterol Dry Powder Inhaler 2.5 μg19.73± 35.48
Abediterol Pressurised Metered-dose Inhaler 2.5μg15.59± 29.57

Adverse events — posted to ClinicalTrials.gov

Time frame: From the time of informed consent, throughout the treatment period and including the follow-up period (ie, 2 weeks after last IP dose). Treatment-emergent adverse events were those reported after the first dose of IP up to 30 days after last IP dose.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Abediterol Dry Powder Inhaler 0.156 μg
Serious: 0/29 (0%)
Deaths: 0/29
Abediterol Dry Powder Inhaler 2.5 μg
Serious: 0/29 (0%)
Deaths: 0/29
Abediterol Pressurised Metered-dose Inhaler 0.05μg
Serious: 0/30 (0%)
Deaths: 0/30
Abediterol Pressurised Metered-dose Inhaler 0.156 μg
Serious: 0/30 (0%)
Deaths: 0/30
Abediterol Pressurised Metered-dose Inhaler 2.5μg
Serious: 0/30 (0%)
Deaths: 0/30
Placebo
Serious: 0/29 (0%)
Deaths: 0/29
Other adverse events (4 terms — click to expand)

ReactionSystemAbediterol Dry Powder Inha…Abediterol Dry Powder Inha…Abediterol Pressurised Met…Abediterol Pressurised Met…Abediterol Pressurised Met…Placebo
HeadacheNervous system disorders
ToothacheGastrointestinal disorders
NasopharyngitisInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders

Data from ClinicalTrials.gov NCT02777827 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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