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

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

Official Title
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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.

Conditions
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Asthma

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male and female patients aged 18-70 years (both included). Clinical diagnosis of persistent asthma (according to GINA guidelines 2009 update) for at least 6 months prior to screening. Screening FEV1 value of 60% < FEV1 ≤ 85% of the predicted normal value. FEV1 reversibility ≥ 12% and an absolute increase of at least 200 ml over baseline value after inhalation of 400µg (four inhalations) of salbutamol. Pre-dose FEV1 value of first treatment period within the range of ± 20% of the FEV1 measured at screening prior to salbutamol inhalation. Patients on a stable dose and regimen Exclusion Criteria: Current smokers, former smokers within the last 6 months, or ex-smokers with a history of more than 10 pack-years. Patients diagnosed with COPD. Recent Respiratory tract infections within 6 weeks before Screening Visit. 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. Clinically significant respiratory conditions. Clinically significant cardiovascular conditions. Patients unable to properly use a dry powder or pMDI inhaler device or unable to perform acceptable spirometry. Clinically relevant abnormalities laboratory, ECG parameters or physical examination results at the screening evaluation that in the investigator's opinion, preclude study participation. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD