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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Chiesi Farmaceutici S.p.A.
Information provided by (Responsible Party):
Marc Decramer, Katholieke Universiteit Leuven
ClinicalTrials.gov Identifier:
NCT01466712
First received: November 4, 2011
Last updated: July 29, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
COPD
Emphysema
Small Airway Disease
Drug: Tiotropium + formoterol/beclometasone
Drug: tiotropium + placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Katholieke Universiteit Leuven:

Primary Outcome Measures:
  • 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). [ Time Frame: Before run-in ] [ Designated as safety issue: No ]
    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).

  • 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). [ Time Frame: at randomization ] [ Designated as safety issue: No ]
    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).

  • 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). [ Time Frame: at the end of each treatment period of 4 weeks ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Relate the abnormalities found in tests of small airway function with the findings of probe-based confocal laser endomicroscopy [ Time Frame: Before run-in at the end of each treatment period of 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: drug code number B10356

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01466712

Locations
Belgium
University Hospitals Leuven
Leuven, Flanders, Belgium, 3000
Sponsors and Collaborators
Katholieke Universiteit Leuven
Chiesi Farmaceutici S.p.A.
Investigators
Principal Investigator: Marc Decramer, Md, PhD University Hospitals Leuven
  More Information

No publications provided

Responsible Party: Marc Decramer, Principal Investigator, Katholieke Universiteit Leuven
ClinicalTrials.gov Identifier: NCT01466712     History of Changes
Other Study ID Numbers: S53020
Study First Received: November 4, 2011
Last Updated: July 29, 2013
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

Additional relevant MeSH terms:
Emphysema
Pulmonary Emphysema
Pulmonary Disease, Chronic Obstructive
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Beclomethasone
Formoterol
Tiotropium
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Parasympatholytics
Cholinergic Antagonists

ClinicalTrials.gov processed this record on July 20, 2014