Clinical trial NCT01691482: A Study to Look at Day to Day Changes in Lung Function in COPD Subjects Taking Albuterol/Salbutamol and Ipratropium
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-09-24
Enrollment: 56
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Variability in Daily FEV1, Estimated by Coefficient of Variation
timeFrame: up to 10 days
measure: Variability in Daily FEV1, Estimated by Half Range (i.e., Half the Difference Between Maximum and Minimum Values)
timeFrame: up to 10 days
Secondary outcomes:
measure: The Maximal Bronchodilator Response for the First Administered Agent
timeFrame: up to 10 days
measure: Percentage of Days for Which Participants Achieved a >=12% and 200 Milliliter (mL) Increase From Baseline in FEV1
timeFrame: up to 35 days
measure: Percentage of Days for Which Participants Achieved a Threshold Increase From Baseline in FEV1 of 100 mL, 200 mL, and 250 mL
timeFrame: up to 35 days
measure: Variability in Daily Inspiratory Capacity (IC), Estimated by Coefficient of Variation
timeFrame: up to 10 days
measure: Variability in Daily IC, Estimated by Half Range (i.e., Half the Difference Between Maximum and Minimum)
timeFrame: up to 10 days
Other outcomes:
Locations:
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.