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

Asthma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01425801
• Other study ID #: M/100977/202
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2011
• Est. completion date: February 1, 2012

Study information

• Verified date: April 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: February 1, 2012
• Est. primary completion date: February 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• LAS100977 0.313 µg
Dry powder inhalation, once-daily, single-dose
• LAS100977 0.625 µg
Dry powder inhalation, once-daily, single-dose
• LAS100977 1.25 µg
Dry powder inhalation, once-daily, single-dose
• LAS100977 2.5 µg
Dry powder inhalation, once-daily, single-dose
• Salbutamol 400 µg
Pressurized inhalation suspension, once-daily, single-dose
• Salbutamol placebo
Pressurized inhalation, once-daily
• LAS100977 placebo
Dry powder inhalation, once-daily

Locations

Country	Name	City	State
Germany	Almirall Investigational Sites#1	Berlin
Germany	Almirall Investigational Sites#4	Berlin
Germany	Almirall Investigational Sites#6	Berlin
Germany	Almirall Investigational Sites#3	Frankfurt
Germany	Almirall Investigational Sites#2	Grosshansdorf
Germany	Almirall Investigational Sites#8	Hamburg
Germany	Almirall Investigational Sites#5	Wiesbaden
United Kingdom	Almirall Investigational Sites#2	London
United Kingdom	Almirall Investigational Sites#1	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Synopsis-M-100977-202