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

• ClinicalTrials.gov Identifier: NCT01425801
• Recruitment Status: Completed
• First Posted: August 30, 2011
• Results First Posted: January 26, 2018
• Last Update Posted: May 8, 2018
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: LAS100977 0.313 μg; Drug: LAS100977 0.625 μg; Drug: LAS100977 1.25 μg; Drug: LAS100977 2.5 μg; Drug: Salbutamol 400 μg; Drug: Salbutamol placebo; Drug: LAS100977 placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: August 1, 2011
• Actual Primary Completion Date: February 1, 2012
• Actual Study Completion Date: February 1, 2012

Arms and Interventions

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: LAS100977 1.25 μg; Dry powder inhalation, once-daily, single-dose; Drug: Salbutamol placebo; Pressurized inhalation, once-daily
Experimental: LAS100977 2.5 μg; Single-dose LAS100977 2.5 μg, during double-blind treatment period	Drug: LAS100977 2.5 μg; Dry powder inhalation, once-daily, single-dose; Drug: Salbutamol placebo; Pressurized inhalation, once-daily
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: LAS100977 0.313 μg; Dry powder inhalation, once-daily, single-dose; Drug: Salbutamol placebo; Pressurized inhalation, once-daily

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]
   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.

Secondary Outcome Measures :

1. Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]
   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.
2. Peak Forced Expiratory Volume in One Second (FEV1) [ Time Frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]
   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.
3. Time to Peak Forced Expiratory Volume in One Second (FEV1) [ Time Frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]
   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.
4. Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Baseline and +23 h and +24 h post-dose ]
   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.
5. Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1 [ Time Frame: 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 ]
   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.
6. Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint [ Time Frame: 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 ]
   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.
7. Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint [ Time Frame: 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 ]
   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.
8. Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint [ Time Frame: 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 ]
   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.
9. Change From Baseline in Peak Forced Vital Capacity (FVC) [ Time Frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose ]
   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.
10. Peak Forced Vital Capacity (FVC) [ Time Frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h ]
    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.
11. Time to Peak Forced Vital Capacity (FVC) [ Time Frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h ]
    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.
12. Change From Baseline to Trough Forced Vital Capacity (FVC) [ Time Frame: Baseline and +23 h +24 h post-dose ]
    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.
13. Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC) [ Time Frame: 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 ]
    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.
14. Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint [ Time Frame: 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 ]
    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.
15. Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint [ Time Frame: 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 ]
    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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Germany

Almirall Investigational Sites#6

Berlin, Germany, 10117

Almirall Investigational Sites#4

Berlin, Germany, 14050

Almirall Investigational Sites#1

Berlin, Germany, 14057

Almirall Investigational Sites#3

Frankfurt, Germany, 60596

Almirall Investigational Sites#2

Grosshansdorf, Germany, 22927

Almirall Investigational Sites#8

Hamburg, Germany, 20249

Almirall Investigational Sites#5

Wiesbaden, Germany, 65187

United Kingdom

Almirall Investigational Sites#2

London, United Kingdom, W1G 8HT

Almirall Investigational Sites#1

Manchester, United Kingdom, M3 9QZ

Sponsors and Collaborators

AstraZeneca

Investigators

• Study Director: Carol Astbury, PhD; AstraZeneca

More Information

Additional Information:

Synopsis-M-100977-202 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 β2-adrenergic agonist, in asthma; a Phase II, randomized study. BMC Pulm Med. 2014 Nov 14;14:176. doi: 10.1186/1471-2466-14-176.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01425801
• Other Study ID Numbers: M/100977/202
• First Posted: August 30, 2011
• Results First Posted: January 26, 2018
• Last Update Posted: May 8, 2018
• Last Verified: April 2018

Keywords provided by AstraZeneca:

COPD

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Albuterol; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Tocolytic Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action