Evaluate the Effects of Formoterol and Beclomethasone Dipropionate Combination Therapy on Small Airways Function

Randomized Double-blind Placebo-controlled Crossover Study to Evaluate the Effects of Formoterol and Beclomethasone Dipropionate Combination Therapy on Small Airways Function in COPD Patients.

Inuvair® is a novel fixed combination product used in the treatment of asthma and under clinical development for the treatment of COPD. Thanks to the extrafine particle size, it is able to target the whole bronchial tree, including the small airways and hence, is expected to act in these airways and it may thus be beneficial in COPD in that sense. In COPD, its action on the small airways is not directly demonstrated thus far. By way of contrast, dear evidence is present that treatment with bronchodilators alone does not beneficially alter small airway function. The study hypothesis states that the effects of inhaled corticosteroids or ICS/LABA combinations on small airway is present and can be objectivated.

Study Overview

• Status: Unknown
• Conditions: Emphysema; COPD; Small Airway Disease
• Intervention / Treatment: Drug: Tiotropium + formoterol/beclometasone; Drug: tiotropium + placebo

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Flanders
    • Leuven, Flanders, Belgium, 3000
      • University Hospitals Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical diagnosis COPD according to last updated GOLD guidelines (post- bronchodilator FEV/FVC below 0,70, FEV1 <80% predicted)
• ex-smokers (ie 1 year from the last cigarette) with at least 10 pack years.
• GOLD stage II and III (FEV1 > 30% predicted)
• by preference naïve to inhaled corticosteroids; in those taking inhaled corticosteroids this medication will be stopped 1 month prior to enrollment in the study
• Patients must have proven small airways dysfunction on routine spirometry as reflected by a drop in FEF25-75 and FEF75 of at least 50%. Moreover, patients must have proven small airways dysfunction on MBW as reflected by Sacin >0,120 that is considered abnormal.

Exclusion Criteria:

• Current smoking
• Active COPD exacerbation
• gold stage I and IV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tiotropium+formoterol/beclomethasone; run-in of 4 weeks with thiotropium cross-over after first treatment period of 4 weeks	Drug: Tiotropium + formoterol/beclometasone; Tiotropium 18 µg/dose once daily (handihaler device) + formoterol, fumarate 6µg + beclometasone, dipropionate 100µg / dose (Pressurised inhaler): 2 puffs bid, for one month.; Other Names: Inuvair (B10356)
Sham Comparator: tiotropium+placebo; cross-over cfr arm1	Drug: tiotropium + placebo; Tiotropium 18 µg/dose once daily (handihaler device) + placebo (Pressurised inhaler): 2 puffs bid, for one month.; Other Names: drug code number B10356

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiologically measured small airway function based on MBW variables (Scond and Sacin) and lung functional variables (N2-washout, studying the plateau of phase III and closing volume).	After a run-in period of 4 weeks in which all patients will receive Tiotropium 18 pig per day as treatment for their disease, they will be randomized in two groups: one group receiving Tiotropium + placebo and another group receiving Tiotropium + Inuvair 2 puffs bid, for one month. After this treatment period, there will be a wash-out period of 4 weeks (with tiotropium as run-in).	Before run-in
Physiologically measured small airway function based on MBW variables (Scond and Sacin) and lung functional variables (N2-washout, studying the plateau of phase III and closing volume).	After a run-in period of 4 weeks in which all patients will receive Tiotropium 18 pig per day as treatment for their disease, they will be randomized in two groups: one group receiving Tiotropium + placebo and another group receiving Tiotropium + Inuvair 2 puffs bid, for one month. After this treatment period, there will be a wash-out period of 4 weeks (with tiotropium as run-in).	at randomization
Physiologically measured small airway function based on MBW variables (Scond and Sacin) and lung functional variables (N2-washout, studying the plateau of phase III and closing volume).	After a run-in period of 4 weeks in which all patients will receive Tiotropium 18 pig per day as treatment for their disease, they will be randomized in two groups: one group receiving Tiotropium + placebo and another group receiving Tiotropium + Inuvair 2 puffs bid, for one month. After this treatment period, there will be a wash-out period of 4 weeks (with tiotropium as run-in).	at the end of each treatment period of 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Relate the abnormalities found in tests of small airway function with the findings of probe-based confocal laser endomicroscopy	Before run-in at the end of each treatment period of 4 weeks

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Marc Decramer, MD, PhD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: November 4, 2011
• First Submitted That Met QC Criteria: November 4, 2011
• First Posted (Estimate): November 8, 2011

Study Record Updates

• Last Update Posted (Estimate): July 30, 2013
• Last Update Submitted That Met QC Criteria: July 29, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Emphysema; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Beclomethasone; Tiotropium Bromide; Formoterol Fumarate
• Other Study ID Numbers: S53020