Effect of Aclidinium/Formoterol on Nighttime Lung Function and Morning Symptoms in Chronic Obstructive Pulmonary Disease

NCT02429765 | Completed Phase 4 DMC

• 1 other identifier: DMED-1744-14
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

A number of studies have documented poor sleep quality and troublesome symptoms (breathlessness, cough and sputum production) upon awakening in patients with COPD. However, the investigators know very little about measurements of respiratory mechanics (i.e., lung volumes, respiratory pressures, diaphragm function, etc) during sleep in these patients. The investigators also know little about how modern bronchodilator therapies, or the timing of when they are taken, affect respiratory mechanics during sleep or the severity of early morning respiratory symptoms. COPD is often treated with inhaled bronchodilator medications which are used to open up airways and make it easier for air to get in and out of the lungs. The investigators are studying the effects of a new inhaler that contains two different types of long-acting bronchodilator: formoterol \[a long-acting beta2-agonist (LABA)\] and aclidinium bromide \[a long-acting muscarinic antagonist (LAMA) or anticholinergic\]. Initial studies have shown that this combination therapy taken twice daily can improve some lung function measurements and respiratory symptoms in patients with moderate to severe COPD. There are also reports that evening administration of this medication may provide important advantages in patients with dominant nighttime and early morning symptoms. It is thought that sustained bronchodilation and lung deflation during the night may improve respiratory mechanics, diaphragmatic function, pulmonary gas exchange, sleep quality, and reduce severity of morning symptoms. This study will be the first to explore the effects of a nighttime dose of aclidinium/formoterol combination therapy on detailed measurements of respiratory mechanics and early morning symptoms in COPD. This study will also give us a better understanding of the mechanisms of early morning respiratory symptoms and their improvement with bronchodilators.

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• Morning trough inspiratory capacity (IC) as measured by a spirometer

  Early morning IC (\~6:00am) will be measured to assess improvements in lung hyperinflation in response to the evening dose (\~8:00pm) of a twice-daily bronchodilator vs. placebo.

  10 hours after the evening dose of randomized study drug

Secondary Outcomes (7)

• Early Morning Symptoms of COPD Instrument (EMSCI)

  Upon awakening in the morning: 10 hours after the evening dose of randomized study drug

• Distribution of sleep stages obtained during polysomnography

  Participants will be followed for the duration of the night after the evening dose of randomized study medication: between bedtime at 10pm and upon waking or 5:45am, whichever is sooner

• Changes in the forced expired volume in 1 second (FEV1) as measured by a spirometer

  Measurements will be collected at 2-hr intervals after the evening dose of randomized study medication (i.e., 2, 4, 6, 8 and 10 hrs post-dose)

• Changes in IC as measured by a spirometer

  Measurements will be collected at 2-hr intervals after the evening dose of randomized study medication (i.e., 2, 4, 6, 8 and 10 hrs post-dose)

• Morning trough functional residual capacity (FRC) as measured by body plethysmography

  10 hours after the evening dose of randomized study drug

Study Arms (2)

ACL/FOR

ACTIVE COMPARATOR

The evening dose of twice-daily dual bronchodilator medication will consist of aclidinium/formoterol 400/12mcg . After 2-weeks of treatment with twice-daily aclidinium/formoterol 400/12mcg, subjects will be randomized to receive an evening dose consisting of active drug or placebo.

Drug: ACL/FOR

Placebo

PLACEBO COMPARATOR

The evening dose of twice-daily dual bronchodilator medication will consist of a placebo inhaler. After 2-weeks of treatment with twice-daily aclidinium/formoterol 400/12mcg, subjects will be randomized to receive an evening dose consisting of active drug or placebo.

Drug: Placebo

Interventions

ACL/FOR DRUG

Also known as: aclidinium/formoterol, Duaklir

ACL/FOR

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) 30-79%predicted);
• Resting functional residual capacity (FRC) \>120% predicted;
• Clinically stable and on stable triple therapy with an ICS/LABA and tiotropium;
• Symptomatic: Baseline Dyspnea Index ≤8 and answer "in the morning" when asked about what time of day their COPD symptoms are worst.

You may not qualify if:

• A diagnosis of sleep disordered breathing;
• Nocturnal oxygen therapy.

Sponsors & Collaborators

• Queen's University: lead
• AstraZeneca: collaborator

Study Sites (1)

Respiratory Investigation Unit, Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Related Publications (2)

• Domnik NJ, Phillips DB, James MD, Ayoo GA, Taylor SM, Scheeren RE, Di Luch AT, Milne KM, Vincent SG, Elbehairy AF, Crinion SJ, Driver HS, Neder JA, O'Donnell DE. Compensatory responses to increased mechanical abnormalities in COPD during sleep. Eur J Appl Physiol. 2022 Mar;122(3):663-676. doi: 10.1007/s00421-021-04869-0. Epub 2022 Jan 16.

  PMID: 35034195 DERIVED

• Domnik NJ, James MD, Scheeren RE, Ayoo GA, Taylor SM, Di Luch AT, Milne KM, Vincent SG, Phillips DB, Elbehairy AF, Crinion SJ, Driver HS, Neder JA, O'Donnell DE. Deterioration of Nighttime Respiratory Mechanics in COPD: Impact of Bronchodilator Therapy. Chest. 2021 Jan;159(1):116-127. doi: 10.1016/j.chest.2020.06.033. Epub 2020 Jun 27.

  PMID: 32603714 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

aclidinium bromide; Formoterol Fumarate

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)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Denis E O'Donnell, MD, FRCPC

  Queen's University & Kingston General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 7, 2014
• First Posted: April 29, 2015
• Study Start: October 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: July 12, 2019

Record last verified: 2019-07

Locations

CA (1)