Single Dose Study to Assess Efficacy and Safety of 4 Doses of LAS100977 in Chronic Obstructive Pulmonary Disease (COPD) Population

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 Strengths of LAS100977 QD Compared to Placebo and an Active Comparator in Patients With Stable Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

The purpose of this study is to evaluate the pharmacodynamics (bronchodilation) of single doses of inhaled LAS100977 in COPD patients.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: LAS100977; Drug: Reference; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Almirall Investigational Sites#5
  • Berlin, Germany, 14057
    • Almirall Investigational Sites#2
  • Frankfurt, Germany, 60596
    • Almirall Investigational Sites#6
  • Grosshansdorf, Germany, 22927
    • Almirall Investigational Sites#3
  • Hamburg, Germany, 20354
    • Almirall Investigational Sites#7
  • Lübeck, Germany, 23552
    • Almirall Investigational Sites#8
  • Mainz, Germany, 55131
    • Almirall Investigational Sites#1
  • Wiesbaden, Germany, 65187
    • Almirall Investigational Sites#4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and non-pregnant, non-lactating females aged 40 or older.
2. Patients with a clinical diagnosis of COPD, according to the GOLD guidelines and stable airway obstruction.
3. Patients with a post-salbutamol FEV1 equal to or greater than 30% of the predicted value and less than 80% of the predicted value
4. Post-salbutamol FEV1/FVC < 70% at screening visit.
5. Pre-dose FEV1 value of first treatment period within the range of 80-120% of the FEV1 measured at screening prior to salbutamol inhalation.
6. Current, or ex-cigarette smokers (former) with a smoking history of at least 10 pack-years.
7. Patients whose COPD symptoms at the time of randomisation are stable compared to the Screening visit, according to the investigator's medical judgment.

Exclusion Criteria:

1. History or current diagnosis of asthma.
2. A respiratory tract infection or COPD exacerbation in the six weeks prior to the screening visit.
3. Patients who have been hospitalised for an acute COPD exacerbation in the 3 months prior to screening visit.
4. Clinically significant respiratory conditions other than COPD condition.
5. Clinically significant cardiovascular conditions.
6. Patients unable to properly use a dry powder or pMDI inhaler device or unable to perform acceptable spirometry.
7. Clinically relevant abnormalities laboratory, ECG parameters or physical examination results at the screening evaluation that in the investigator's opinion, preclude study participation.
8. 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: Arm #2; Single dose, double blind treatment period	Drug: LAS100977; Dry powder inhalation,Once daily, single dose
Experimental: Arm #3; Single dose, double blind treatment period	Drug: LAS100977; Dry powder inhalation,Once daily, single dose
Experimental: Arm #4; Single dose, double blind treatment period	Drug: LAS100977; Dry powder inhalation,Once daily, single dose
Active Comparator: Arm #5; Single dose, double blind treatment period	Drug: Reference; Dry powder inhalation (capsule),single dose
Placebo Comparator: Arm #6; Single dose, double blind treatment period	Drug: Placebo; Dry powder inhalation or Dry powder inhalation (capsule),Once daily, single dose
Experimental: Arm #1; Single dose, double blind treatment period	Drug: LAS100977; 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 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	Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Normalised Forced Expiratory Volume in One Second (FEV1) Area Under the Curve	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	Day 1
Change From Baseline in 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) 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	Up to Day 2
Absolute Forced Expiratory Volume in One Second (FEV1) Values	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	Up to Day 2
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) 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	Day 1
Time to Peak Forced Expiratory Volume in One Second (FEV1)	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	Day 1
Change From Baseline in 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	Day 2
Change From Baseline in Normalised Forced Vital Capacity (FVC) Area Under the Curve	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	Day 1
Change From Baseline in 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) 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	Up to Day 2
Absolute Forced Vital Capacity (FVC) Values	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	Up to Day 2
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) 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	Day 1
Time to Peak Forced Vital Capacity (FVC)	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	Day 1
Change From Baseline in Inspiratory Capacity (IC)	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	Up to Day 2
Absolute Inspiratory Capacity (IC) Values	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	Up to Day 2

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Beier J, Pujol H, Seoane B, Jimenez E, Astbury C, Massana E, Ruiz S, de Miquel G. Abediterol, a novel long-acting beta2-agonist: bronchodilation, safety, tolerability and pharmacokinetic results from a single-dose, dose-ranging, active-comparator study in patients with COPD. BMC Pulm Med. 2016 Jul 20;16(1):102. doi: 10.1186/s12890-016-0266-5.

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 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): April 10, 2017
• Last Update Submitted That Met QC Criteria: February 27, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: M/100977/25; LBC25