Evaluation of Long-Acting Muscarinic Antagonists in COPD (MAN04)

Proof of Concept Evaluation of Drug-Device Interaction With Aclidinium Bromide Via Genuair® and Tiotropium Bromide Via HandiHaler® in COPD Using Impulse Oscillometry

In chronic obstructive pulmonary disease (COPD), the airways of the lungs are narrowed or blocked. Bronchodilators are drugs usually delivered through inhalers which help open up the airways. Tiotropium is a type of bronchodilator drug known as a long-acting muscarinic antagonist (LAMA). For a long time tiotropium was the only available LAMA. More recently, a new LAMA called aclidinium has been approved for use in COPD. There are potentially important differences between these two medications that might have an impact on the treatment of COPD patients.

In this study we aim to compare the effects of tiotropium and aclidinium in people with COPD. The main comparison will be done using a very sensitive breathing test called impulse oscillometry

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Tiotropium; Drug: Aclidinium

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Asthma and Allergy Research Group, University of Dundee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female volunteers aged 40-80 years with moderate to severe COPD (GOLD Stage 2, 3).
• On inhaled corticosteroids / long-acting beta agonists
• FEV1 30-80% predicted and FEV1/FVC <70%.
• Smoking history ≥10 pack-years.
• Ability to give informed consent
• Agreement for their General Practitioner to be made aware of study participation and to receive feedback as relevant to the participant's well being

Exclusion Criteria:

• Other respiratory diseases such as asthma, bronchiectasis or allergic bronchopulmonary aspergillosis
• A COPD exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement (3 months if hospitalisation has been required)
• Any clinically significant medical condition that may endanger the health or safety of the participant
• Known or suspected sensitivity to/intolerance of investigational medicinal product
• Patients with prostatic hyperplasia, bladder outflow obstruction or glaucoma
• Pregnancy or lactation
• Unable to comply with the procedures of the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tiotropium; Participants receive tiotropium for 2 to 3 weeks.Participants then enter a washout period and after the washout period receive the alternative treatment arm.	Drug: Tiotropium
Experimental: Aclidinium; Participants receive tiotropium for 2 to 3 weeks.Participants then enter a washout period and after the washout period receive the alternative treatment arm.	Drug: Aclidinium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in trough R5 from baseline after chronic dosing	4 to 6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Remaining impulse oscillometry (IOS) variables (R20,R5-R20,X5,AX,RF)	4 to 6 weeks
Spirometry (FEV1, FEF25-75, FVC)	4 to 6 weeks
Relaxed VC (RVC) with RVC to FVC ratio	4 to 6 weeks
Six-minute walk test (includes oxygen saturation measurements and Borg dyspnoea score)	4 to 6 weeks
Domiciliary PIKO-6 measurements for FEV1 and FEV6	4 to 6 weeks
St. George's Respiratory Questionnaire (SGRQ)	4 to 6 weeks
Baseline Dyspnea Index-Transition Dyspnea Index (BDI-TDI)	4 to 6 weeks

Collaborators and Investigators

• Sponsor: University of Dundee
• Collaborators: Almirall Limited
• Investigators: Principal Investigator: Brina Lipworth, MD, University of Dundee

Publications and helpful links

General Publications

• Manoharan A, Morrison AE, Lipworth BJ. Effects of Adding Tiotropium or Aclidinium as Triple Therapy Using Impulse Oscillometry in COPD. Lung. 2016 Apr;194(2):259-66. doi: 10.1007/s00408-015-9839-y. Epub 2016 Jan 13.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: January 15, 2014
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (Estimate): January 17, 2014

Study Record Updates

• Last Update Posted (Actual): April 12, 2019
• Last Update Submitted That Met QC Criteria: April 10, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Pulmonary Disease, Chronic Obstructive; Impulse oscillometry; Long-acting muscarinic antagonists
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Chronic Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide
• Other Study ID Numbers: 2013RC09