Single Dose Study to Assess Efficacy, Safety and Tolerability of LAS100977 in Asthmatic Patients.

A Phase IIa, Randomised, Single Dose, Double-blind, Double-dummy, 6 Way Complete Cross-over, Placebo Controlled Clinical Trial to Assess the Efficacy, Safety and Tolerability of 4 Doses of LAS100977 QD Compared to Placebo and an Active Comparator in Patients With Persistent Asthma.

The purpose of this study is to evaluate the pharmacodynamics of single doses of inhaled LAS100977 QD in patients with persistent asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: LAS100977 0.625 μg; Drug: Salbutamol placebo; Drug: LAS100977 1.25 μg; Drug: LAS100977 2.5 μg; Drug: Salbutamol 400 μg; Drug: LAS100977 placebo; Drug: LAS100977 0.313 μg

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Almirall Investigational Sites#6
  • Berlin, Germany, 14050
    • Almirall Investigational Sites#4
  • Berlin, Germany, 14057
    • Almirall Investigational Sites#1
  • Frankfurt, Germany, 60596
    • Almirall Investigational Sites#3
  • Grosshansdorf, Germany, 22927
    • Almirall Investigational Sites#2
  • Hamburg, Germany, 20249
    • Almirall Investigational Sites#8
  • Wiesbaden, Germany, 65187
    • Almirall Investigational Sites#5
• United Kingdom
  • London, United Kingdom, W1G 8HT
    • Almirall Investigational Sites#2
  • Manchester, United Kingdom, M3 9QZ
    • Almirall Investigational Sites#1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult male and female patients aged 18-70 years (both included).
2. Clinical diagnosis of persistent asthma (according to GINA guidelines 2009 update) for at least 6 months prior to screening.
3. Screening FEV1 value of 60% < FEV1 ≤ 85% of the predicted normal value.
4. FEV1 reversibility ≥ 12% and an absolute increase of at least 200 ml over baseline value after inhalation of 400µg (four inhalations) of salbutamol.
5. Pre-dose FEV1 value of first treatment period within the range of ± 20% of the FEV1 measured at screening prior to salbutamol inhalation.
6. Patients on a stable dose and regimen

Exclusion Criteria:

1. Current smokers, former smokers within the last 6 months, or ex-smokers with a history of more than 10 pack-years.
2. Patients diagnosed with COPD.
3. Recent Respiratory tract infections within 6 weeks before Screening Visit.
4. Intubation (ever) or hospitalization for longer than 24 hours for the management of an asthma exacerbation within the preceding 6 weeks of the screening visit.
5. Clinically significant respiratory conditions.
6. Clinically significant cardiovascular conditions.
7. Patients unable to properly use a dry powder or pMDI inhaler device or unable to perform acceptable spirometry.
8. Clinically relevant abnormalities laboratory, ECG parameters or physical examination results at the screening evaluation that in the investigator's opinion, preclude study participation.
9. Patients who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required washout period for a particular prohibited medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LAS100977 0.625 μg; Single-dose LAS100977 0.625 μg, during double-blind treatment period	Drug: LAS100977 0.625 μg; Dry powder inhalation, once-daily, single-dose; Drug: Salbutamol placebo; Pressurized inhalation, once-daily
Experimental: LAS100977 1.25 μg; Single-dose LAS100977 1.25 μg, during double-blind treatment period	Drug: Salbutamol placebo; Pressurized inhalation, once-daily; Drug: LAS100977 1.25 μg; Dry powder inhalation, once-daily, single-dose
Experimental: LAS100977 2.5 μg; Single-dose LAS100977 2.5 μg, during double-blind treatment period	Drug: Salbutamol placebo; Pressurized inhalation, once-daily; Drug: LAS100977 2.5 μg; Dry powder inhalation, once-daily, single-dose
Active Comparator: Salbutamol; Single-dose salbutamol 400 μg, during double-blind treatment period	Drug: Salbutamol 400 μg; Pressurized inhalation suspension, once-daily, single-dose; Drug: LAS100977 placebo; Dry powder inhalation, once-daily
Placebo Comparator: Placebo; Placebo to LAS100977, and placebo to salbutamol	Drug: Salbutamol placebo; Pressurized inhalation, once-daily; Drug: LAS100977 placebo; Dry powder inhalation, once-daily
Experimental: LAS100977 0.313 μg; Single-dose LAS100977 0.313 μg, during double-blind treatment period	Drug: Salbutamol placebo; Pressurized inhalation, once-daily; Drug: LAS100977 0.313 μg; Dry powder inhalation, once-daily, single-dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Peak Forced Expiratory Volume in One Second (FEV1)	The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.	+15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Time to Peak Forced Expiratory Volume in One Second (FEV1)	The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.	+15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1)	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). Trough at Day 2 was computed as the average of the two values measured at 23 and 24 hours after administration of the morning dose of investigational medicinal product on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.	Baseline and +23 h and +24 h post-dose
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1	FEV1 was normalized to baseline. Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h
Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Change From Baseline in Peak Forced Vital Capacity (FVC)	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Peak Forced Vital Capacity (FVC)	The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.	+15 min, +30 min, +1 h, +2 h, +3 h, +4 h
Time to Peak Forced Vital Capacity (FVC)	The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.	+15 min, +30 min, +1 h, +2 h, +3 h, +4 h
Change From Baseline to Trough Forced Vital Capacity (FVC)	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). Trough at Day 2 was computed as the average of the two values measured at 23 and 24 hours after administration of the morning dose of investigational medicinal product on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.	Baseline and +23 h +24 h post-dose
Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC)	FVC was normalized to baseline. Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h
Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint	Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.	Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Carol Astbury, PhD, AstraZeneca

Publications and helpful links

General Publications

• Singh D, Pujol H, Ribera A, Seoane B, Massana E, Astbury C, Ruiz S, de Miquel G. A dose-ranging study of the bronchodilator effects of abediterol (LAS100977), a long-acting beta2-adrenergic agonist, in asthma; a Phase II, randomized study. BMC Pulm Med. 2014 Nov 14;14:176. doi: 10.1186/1471-2466-14-176.

Helpful Links

• Synopsis-M-100977-202

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: August 29, 2011
• First Submitted That Met QC Criteria: August 29, 2011
• First Posted (Estimate): August 30, 2011

Study Record Updates

• Last Update Posted (Actual): May 8, 2018
• Last Update Submitted That Met QC Criteria: May 7, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: M/100977/202