A Study to Look at Day to Day Changes in Lung Function in COPD Subjects Taking Albuterol/Salbutamol and Ipratropium

A 4-Week Randomized Cross-Over Study to Evaluate Daily Lung Function Following the Administration of Albuterol/Salbutamol and Ipratropium in Subjects With Chronic Obstructive Pulmonary Disease

The objective of this study is to assess the daily variation in bronchodilator response to an inhaled short acting beta2-agonist (albuterol/salbutamol) and an inhaled short acting anticholinergic (ipratropium) individually and when used in combination in subjects with COPD.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Albuterol/salbutamol; Drug: Ipratropium

Detailed Description

Beta2-agonist and anticholinergics are a principle component of the pharmacologic management of chronic obstructive pulmonary disease COPD. It has been demonstrated that the combination of a short acting beta2-agonist and a short acting anticholinergic yields greater efficacy as measured by FEV1 when compared with the response to the individual short acting bronchodilators. However, daily bronchial response to these agents is poorly understood. It is also poorly understood how the variation in magnitude of the response to the individual agents and how the variation in response for one agent coincides with the variation in response to the other agent. This study will seek to define the pattern of response of each individual agent and the relationship between them. The study will also explore if the combination of the two agents leads to less variation in response compared to the individual agents. This is a randomized, open label, two period cross-over study. Eligible subjects will be randomized to a sequence of either albuterol/salbutamol via metered-dose inhaler (MDI) followed by ipratropium via MDI or the same dose of each bronchodilator given in the opposite order. Each study period will consist of 10 clinic visits to be conducted over 10 to 14 days.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9LT
    • GSK Investigational Site
• United States
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site

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:

• Subjects must give their signed and dated written informed consent to participate.
• Subjects 40 years of age or older at Visit 1.
• Male or female subjects .
• An established clinical history of COPD.
• Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years at Visit 1.
• A post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a post-albuterol/salbutamol FEV1 of >=30 and <= 70% of predicted normal values at Visit 1 calculated using NHANES III reference equations .

Exclusion Criteria:

• A current diagnosis of asthma
• Women who are pregnant of lactating or are planning on becoming pregnant during the study.
• Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
• Participation in pulmonary rehabilitation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Albuterol/salbutamol followed by ipratropium; Subjects will recieve daily albuterol/salbutamol followed by ipratropium which will be adminstered one hour after adminstration of albuterol/salbutamol	Drug: Albuterol/salbutamol; Albuterol/salbutamol (daily)
Active Comparator: Ipratropium followed by albuterol/salbutamol; Subjects will recieve daily ipratropium followed by albuterol/salbutamol which will be adminstered one hour after adminstration of ipratropium	Drug: Ipratropium; Ipratropium (daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability in Daily FEV1, Estimated by Coefficient of Variation	FEV1 is the maximal amount of air that can be forcefully exhaled in one second. During each study period, pre- and post-bronchodilator spirometry for evaluation of FEV1 was performed at study visits as follows: prior to administration of the first short-acting bronchodilator, approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours). Variability in daily FEV1 was measured as the fluctuation around the mean FEV1 data collected from Day 1 to Day 10. Variability was measured by the coefficient of variation (CV) and the half range. The CV is the dispersion of the data around the mean, whereas the half range method is the difference between the maximum and minimum FEV1 values.	up to 10 days
Variability in Daily FEV1, Estimated by Half Range (i.e., Half the Difference Between Maximum and Minimum Values)	FEV1 is the maximal amount of air that can be forcefully exhaled in one second. During each study period, pre- and post-bronchodilator spirometry for evaluation of FEV1 was performed at study visits as follows: prior to administration of the first short-acting bronchodilator, approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours). Variability in daily FEV1 was measured as the fluctuation around the mean FEV1 data collected from Day 1 to Day 10. Variability was measured by the coefficient of variation (CV) and the half range. The CV is the dispersion of the data around the mean, whereas the half range method is half the difference between the maximum and minimum FEV1 values.	up to 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Maximal Bronchodilator Response for the First Administered Agent	The maximal bronchodilator response for the first administered agent is defined as the FEV1 (the maximal amount of air that can be forcefully exhaled in one second) 1 hour post-dose of the first bronchodilator minus the pre-dose. The maximal bronchodilator response for the second agent is defined as the FEV1 1 hour post-dose of the second bronchodilator minus the FEV1 at 1 hour post-dose of the first bronchodilator. The maximal bronchodilator response for the combination is defined as the FEV1 (the maximal amount of air that can be forcefully exhaled in one second) at 1 hour post-administration of the second bronchodilator minus the corresponding pre-dose FEV1. Derived FEV1 response is FEV1 change from 0 hours (0H) for the first agent assessment (at 1 hour [1H]); change from 1H for the second agent assessment (at 2 hours [2H]); and change from 0H for the combination assessment (at 2H). Data were adjusted for FEV1, smoking status, and center.	up to 10 days
Percentage of Days for Which Participants Achieved a >=12% and 200 Milliliter (mL) Increase From Baseline in FEV1	FEV1 is the maximal amount of air that can be forcefully exhaled in one second. During each study period, pre- and post-bronchodilator spirometry for evaluation of FEV1 was performed at study visits as follows: approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours).	up to 35 days
Percentage of Days for Which Participants Achieved a Threshold Increase From Baseline in FEV1 of 100 mL, 200 mL, and 250 mL	FEV1 is the maximal amount of air that can be forcefully exhaled in one second. During each study period, pre- and post-bronchodilator spirometry for evaluation of FEV1 was performed at study visits as follows: approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours).	up to 35 days
Variability in Daily Inspiratory Capacity (IC), Estimated by Coefficient of Variation	IC is the the total amount of air that can be drawn into the lungs after normal expiration. During each study period, pre- and post-bronchodilator spirometry for evaluation of IC was performed at study visits as follows: prior to administration of the first short-acting bronchodilator, approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours). Variability in daily IC was measured as the fluctuation around the mean IC data collected from Day 1 to Day 10. Variability was measured by the coefficent of variation (CV) and the half range. The CV is the dispersion of the data around the mean, whereas the half range method is the difference between the maximum and minimum IC values.	up to 10 days
Variability in Daily IC, Estimated by Half Range (i.e., Half the Difference Between Maximum and Minimum)	IC is the the total amount of air that can be drawn into the lungs after normal expiration. During each study period, pre- and post-bronchodilator spirometry for evaluation of IC was performed at study visits as follows: prior to administration of the first short-acting bronchodilator, approximately 1 hour after administration of the first bronchodilator (1 hour), and approximately 1 hour after administration of the second short-acting bronchodilator (2 hours). Variability in daily IC was measured as the fluctuation around the mean IC data collected from Day 1 to Day 10. Variability was measured by the coefficent of variation (CV) and the half range. The CV is the dispersion of the data around the mean, whereas the half range method is half the difference between the maximum and minimum IC values.	up to 10 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Singh D, Zhu CQ, Sharma S, Church A, Kalberg CJ. Daily variation in lung function in COPD patients with combined albuterol and ipratropium: results from a 4-week, randomized, crossover study. Pulm Pharmacol Ther. 2015 Apr;31:85-91. doi: 10.1016/j.pupt.2014.08.010. Epub 2014 Sep 6.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: July 23, 2012
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 22, 2012

Study Registration Dates

• First Submitted: September 20, 2012
• First Submitted That Met QC Criteria: September 20, 2012
• First Posted (Estimate): September 24, 2012

Study Record Updates

• Last Update Posted (Actual): June 20, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Ipratropium
• Other Study ID Numbers: 114956

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 114956
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 114956
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 114956
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 114956
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 114956
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 114956
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 114956
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register