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

Phase 2

Completed

• Conditions: Asthma
• Interventions: Drug: LAS100977 1.25 μg; Drug: Salbutamol 400 μg; Drug: LAS100977 0.313 μg; Drug: LAS100977 0.625 μg; Drug: LAS100977 2.5 μg; Drug: Salbutamol placebo; Drug: LAS100977 placebo

• Registration Number: NCT01425801
• Lead Sponsor: AstraZeneca

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2011-08-01
• Study First Submitted: 2011-08-29
• Study First Submitted QC: 2011-08-29
• Study First Posted: 2011-08-30
• Primary Completion: 2012-02-01
• Study Completion: 2012-02-01
• Results First Submitted: 2017-02-27
• Results First Submitted QC: 2017-06-08
• Results First Posted: 2018-01-26
• Status Verified: 2018-04
• Last Update Submitted: 2018-05-07
• Last Update Posted: 2018-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
LAS100977 1.25 μg	LAS100977 1.25 μg	Single-dose LAS100977 1.25 μg, during double-blind treatment period
Salbutamol	Salbutamol 400 μg	Single-dose salbutamol 400 μg, during double-blind treatment period
LAS100977 0.313 μg	LAS100977 0.313 μg	Single-dose LAS100977 0.313 μg, during double-blind treatment period
LAS100977 0.625 μg	LAS100977 0.625 μg	Single-dose LAS100977 0.625 μg, during double-blind treatment period
LAS100977 2.5 μg	LAS100977 2.5 μg	Single-dose LAS100977 2.5 μg, during double-blind treatment period
Salbutamol	LAS100977 placebo	Single-dose salbutamol 400 μg, during double-blind treatment period
Placebo	Salbutamol placebo	Placebo to LAS100977, and placebo to salbutamol
LAS100977 1.25 μg	Salbutamol placebo	Single-dose LAS100977 1.25 μg, during double-blind treatment period
Placebo	LAS100977 placebo	Placebo to LAS100977, and placebo to salbutamol
LAS100977 0.313 μg	Salbutamol placebo	Single-dose LAS100977 0.313 μg, during double-blind treatment period
LAS100977 0.625 μg	Salbutamol placebo	Single-dose LAS100977 0.625 μg, during double-blind treatment period
LAS100977 2.5 μg	Salbutamol placebo	Single-dose LAS100977 2.5 μg, during double-blind treatment period

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)	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

Name	Time	Method
Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint	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.
Peak Forced Expiratory Volume in One Second (FEV1)	+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.
Peak Forced Vital Capacity (FVC)	+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.
Time to Peak Forced Vital Capacity (FVC)	+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.
Time to Peak Forced Expiratory Volume in One Second (FEV1)	+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.
Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint	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.
Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint	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.
Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)	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.
Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1)	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.
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1	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.
Change From Baseline in Peak Forced Vital Capacity (FVC)	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.
Change From Baseline to Trough Forced Vital Capacity (FVC)	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.
Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC)	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.
Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint	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.
Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint	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.

Trial Locations

Locations (7)

Almirall Investigational Sites#5; 🇩🇪 Wiesbaden, Germany

Almirall Investigational Sites#6; 🇩🇪 Berlin, Germany

Almirall Investigational Sites#4; 🇩🇪 Berlin, Germany

Almirall Investigational Sites#1; 🇬🇧 Manchester, United Kingdom

Almirall Investigational Sites#8; 🇩🇪 Hamburg, Germany

Almirall Investigational Sites#2; 🇬🇧 London, United Kingdom

Almirall Investigational Sites#3; 🇩🇪 Frankfurt, Germany