Evaluation of Long-Acting Muscarinic Antagonists in COPD

Study Overview
=================
Brief Summary
-----------------
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

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

Conditions
-----------------
Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
-----------------
* Drug: Tiotropium
* Drug: Aclidinium


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tiotropium<br>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<br> <br> |
| Experimental: Aclidinium<br>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<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Impulse oscillometry, Pulmonary Disease, Chronic Obstructive, Long-acting muscarinic antagonists