Acute Effect of Aclidinium on Hyperinflation and Ventilation Inhomogeneity in Severe COPD Patients

NCT02181023 | Completed Phase 4 DMC

• 1 other identifier: 960CEC
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

• Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung hyperinflation and flow limitation. These physiopathological modifications are secondary to loss of elastic recoil and bronchial obstruction due to emphysema.
• The cornerstone of COPD treatment is represented by inhaled beta-2 agonists and anticholinergics. The molecules of the latter classes can be characterized by short lasting action (few hours), long acting action (12 hours) or ultra long acting duration of action (24 hours).
• For years the only anticholinergic (or antimuscarinic) drug other than those used by aerosol, was Tiotropium Bromide. Recently two new antimuscarinic agents have been launched on the market: glycopyrronium bromide (once daily) and aclidinium (twice daily).
• The Single Breath Nitrogen Test is capable of identifying the pulmonary closing volume. The part of the curve that reflects lung ventilation inhomogeneity is the slope of phase III
• For COPD patients, the most important characteristic for an inhalatory drug is a prompt action in order to give a quick relief from respiratory symptoms, in particular dyspnoea.
• The objective of this study is to study the acute action of glycopyrronium and aclidinium in terms of reduction of hyperinflation, pulmonary specific resistances, lung volume distribution and dyspnoea at rest in severe COPD patients.
• To our knowledge no study has explored these aspects before.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Hyperinflation; Aclidinium; Glycopyrronium; Volume distribution; Anticholinergic; Pharmacokinetics; Single Breath Nitrogen Test; Phase III

Outcome Measures

Primary Outcomes (2)

• Residual Volume Variation from baseline

  Residual Volume is obtained by performing body plethysmography before study drug inhalation (baseline), and again 5, 15, 30,60 and 180 minutes after inhalation of study drug. The same subject will undergo the same evaluation in the second part of the study, after the crossing over

  At baseline, 5, 15, 30, 60 and 180 minutes after study drug administration

• Functional Residual Capacity variation from baseline

  Functional Residual Capacity (plethysmographic Intra Thoracic Gas Volume - ITGV) is obtained by performing body plethysmography before study drug inhalation (baseline), and again 5, 15, 30,60 and 180 minutes after inhalation of study drug. The same subject will undergo the same evaluation in the second part of the study, after the crossing over

  At baseline, 5, 15, 30, 60 and 180 minutes after study drug administration

Secondary Outcomes (3)

• Phase III slope variation from baseline

  At baseline, 5, 15, 30, 60 and 180 minutes after study drug administration

• Visual Analogical Scale (VAS) for Dyspnoea at rest variation from baseline

  At baseline, 5, 15, 30, 60 and 180 minutes after study drug administration

• Oxygen and Carbon Dioxide variation from baseline

  At baseline and 180 minutes after inhalation of study drug

Other Outcomes (1)

• Specific AirWay Resistances (sRAW) variation from baseline

  At baseline, 5, 15, 30, 60 and 180 minutes after study drug administration

Study Arms (2)

Aclidinium - Glycopyrronium

EXPERIMENTAL

Patients will assume Aclidinium Bromide 322 dry powder by Genuair inhaler and Glycopyrronium 44 dry powder inhaler by Breezehaler inhaler (placebo) after 72 hours from inhalatory therapy washout (only short acting bronchodilators permitted). Then, after 72 hours of inhalatory drugs washout (only short acting bronchodilators permitted), they will receive Glycopyrronium Bromide 322 mcg via Breezehaler inhaler and Aclidinium Bromide 322 dry powder by Genuair inhaler (placebo).

Drug: Aclidinium Bromide; Drug: Glycopyrronium Bromide

Glycopyrronium - Aclidinium

EXPERIMENTAL

Patients will assume Glycopyrronium Bromide 44 mcg dry powder by Breezehaler inhaler and Aclidinium Bromide 322 dry powder by Genuair inhaler (placebo) after 72 hours of inhalatory therapy washout (only short acting bronchodilators permitted). Then, after 72 hours of inhalatory drugs washout (only short acting bronchodilators permitted) they will receive Aclidinium Bromide 322 mcg via Genuair inhaler and Glycopyrronium Bromide 44 mcg dry powder by Breezehaler inhaler (placebo).

Drug: Aclidinium Bromide; Drug: Glycopyrronium Bromide

Interventions

Aclidinium Bromide DRUG

Aclidinium Bromide 322 mcg inhalation powder via Genuair inhaler (Eklira) Product by Almirall, S.A. Ronda General Mitre, 151. ES-08022 Barcelona, Spain

Also known as: Eklira Genuair (UK), Tudorza Pressair (US), Bretaris Genuair (EU)

Aclidinium - Glycopyrronium; Glycopyrronium - Aclidinium

Glycopyrronium Bromide DRUG

Glycopyrronium Bromide 44 mcg dry powder (capsules) inhaled via Breezehaler inhaler, Seebri - product by Novartis Europharm Limited - Wimblehurst Road, Horsham, West Sussex, RH12 5AB; United Kingdom

Also known as: Seebri Breezhaler

Aclidinium - Glycopyrronium; Glycopyrronium - Aclidinium

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signature of informed consent
• COPD patients with age raging from 50 to 85 years old
• Patients with at least a history of COPD of one year
• COPD patients clinically stable in the last three months
• COPD subjects with Forced Expiratory Volume at one second (FEV1)\<50% of predicted value
• COPD subjects with Residual Volume (RV) \>125% predicted value
• FEV1/Forced Vital Capacity (FVC) \<88% (males) or \<89% (females) of Low Levels of Normality (LLN)
• COPD former or active smokers with at least a smoking history of 20 pack year

You may not qualify if:

• Acute Bronchial Exacerbation at recruitment
• Fertile women with age between 18 and 50 years old or with active period
• Pregnancy
• Subjects enrolled in other clinical trials or that have taken part in one of them in the month preceding the enrollment.
• FEV1/FVC more than 70% of predicted value in basal conditions
• FEV1 more than 70% of predicted value in basal conditions
• Known deficit of alpha 1 antitrypsin
• Subjects that underwent a Lung Volume Reduction Surgery (LVRS)
• Subjects with known positivity to Human Immunodeficiency Virus (HIV)
• Misuse of alcool or drugs
• Lack of compliance in performing respiratory tests
• Subjects not capable to follow the study prescriptions because of psychic disorders or language problems.
• Long Term Oxygen Therapy with flows \> 6 litres per minute (l/min) at rest

Sponsors & Collaborators

• University of Milan: lead
• Fondazione Salvatore Maugeri: collaborator

Study Sites (1)

Fondazione Salvatore Maugeri

Milan, Milan, 20142, Italy

Location

Related Publications (1)

• Santus P, Radovanovic D, Di Marco F, Raccanelli R, Valenti V, Centanni S. Faster reduction in hyperinflation and improvement in lung ventilation inhomogeneity promoted by aclidinium compared to glycopyrronium in severe stable COPD patients. A randomized crossover study. Pulm Pharmacol Ther. 2015 Dec;35:42-9. doi: 10.1016/j.pupt.2015.11.001. Epub 2015 Nov 6.

  PMID: 26549785 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

aclidinium bromide; Glycopyrrolate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pierachille Santus, MD, PhD

  Università degli Studi di Milano-Pneumologia Riabilitativa-Fondazione Salvatore Maugeri-MILANO

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Pulmonary Rehabilitation Unit

Study Record Dates

• First Submitted: July 1, 2014
• First Posted: July 3, 2014
• Study Start: June 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 29, 2014

Record last verified: 2014-10

Locations

IT (1)