Comparison of Ipratropium / Levosalbutamol Fixed Dose Combination and Ipratropium and Levosalbutamol Free Dose Combination Nebuliser Solutions in Stable Chronic Obstructive Pulmonary Disease (COPD) Patients

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the acute bronchodilator effect of the Ipratropium / Levosalbutamol 1.25 mg & 0.5 mg / 2.5 mL fixed dose combination nebuliser solution or Levosalbutamol 1.25 mg / 3 mL nebuliser solution and Ipratropium 500 mcg nebuliser solution in stable moderate-severe-very severe COPD patients.

Official Title
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A Randomized, Parallel Group, Phase III, Non-inferiority Study Comparing Ipratropium / Levosalbutamol Fixed Dose Combination and Ipratropium and Levosalbutamol Free Dose Combination Nebuliser Solutions in Stable Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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COPD

Intervention / Treatment
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* Drug: Ipratropium / Levosalbutamol Fixed Dose Combination
* Drug: Ipratropium + Levosalbutamol Free Dose Combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 40 years and older who have been newly diagnosed or followed up with a diagnosis of COPD. Stable moderate-severe-very severe COPD patients with a post-bronchodilator FEV1/FVC ratio <70% and a postbronchodilator FEV1 value <80% at the screening visit will be included in the study. Symptom status such as chronic cough, sputum production, and progressive dyspnea with the BCSS (Breathlessness, Cough and Sputum Scale) Index will be evaluated, and the COPD staging of the patient with CAT (COPD Assessment Test) and the severity of dyspnea with mMRC (Modified Medical Research Council) will be determined. Patients with at least 10 pack/year smoking status or smoking history (patients who have quit smoking for at least 6 months or more are defined as ex-smokers). Patients who have not experienced an exacerbation in the previous 4 weeks. If the study participant is female; women using appropriate contraception (pregnancy test will be performed at screening visit). Patients with the ability to communicate with the investigator. Patients who accept to comply with the protocol. Patients who sign written informed consent form. Exclusion Criteria: History of hypersensitivity to anticholinergics or SABAs (short acting beta agonist). History of COPD exacerbation or lower respiratory track infection that required treatment with antibiotic, oral or parenteral corticosteroid within the last 3 days prior the screening visit or during the run-in/wash-out period or history of respiratory tract infection that required treatment with antibiotic within the last 14 days prior the screening visit. Hospitalization due to COPD or pneumonia within the last 3 mounts prior the screening visit. SGOT (serum glutamic-oxaloacetic transaminase) >80 IU/L, SGPT (serum glutamic-pyruvic transaminase) >80 IU/L, bilirubin >2.0 mg/dL or creatinine >2.0 mg/dL. History of asthma, significant chronic respiratory diseases (i.e., significant bronchiectasis, interstitial lung diseases, etc.) other than COPD or presence of disease that may be serious and/or potentially affect results of the study. Use of beta-blocker, monoamine oxidase (MAO) inhibitor or tricyclic antidepressant within the last 30 days prior the screening visit Recent (within ≤3 months prior the screening visit) history of heart attack, heart failure, acute ischemic heart disease or presence of serious cardiac arrhythmia requiring drug treatment. Regularly use of daytime CPAP (continuous positive airway pressure) oxygen therapy for longer than 1 hour per day. Initiation of pulmonary rehabilitation within the 3 months prior the screening visit. History of lung volume reduction surgery Drug or alcohol abuse Presence of active tuberculosis History of atopy or allergic rhinitis Presence of active cancer Attenuated live virus vaccination within the last 2 weeks prior the screening visit or during the run-in/wash-out period Pregnancy or lactation Presence of known symptomatic prostatic hypertrophy requiring treatment Presence of known narrow-angle glaucoma requiring treatment Currently participating in another clinical trial or treatment with another investigational study drug within the last month or 6-half-lives, whichever is longer.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipratropium / Levosalbutamol Fixed Dose Combination<br>In this one-day study, patients will be administered Ipratropium / Levosalbutamol 1.25 mg & 0.5 mg / 2.5 mL Nebuliser Solution at 6 hours intervals. | Drug: Ipratropium / Levosalbutamol Fixed Dose Combination<br>* New combination test treatment<br>|
| Active Comparator: Ipratropium + Levosalbutamol Free Dose Combination<br>In this one-day study, patients will be administered Levosalbutamol 1.25 mg/3 mL Inhalation Solution and Ipratropium Nebulization Solution 500 mcg/2 mL at 6 hours intervals. | Drug: Ipratropium + Levosalbutamol Free Dose Combination<br>* Free combination control treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 area under the curve from 0-8 h (FEV1 AUC0-8 h) | Change From Baseline in Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC) 0-8h. | 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 area under the curve from 0-4 h (FEV1 AUC0-4 h) | Change From Baseline in FEV1 AUC (0-4h). | 4 hours | 
| FEV1 AUC4-6 h | Change From Baseline in FEV1 AUC (4-6h). | 4 to 6 hours | 
| FEV1 AUC6-8 h | Change From Baseline in FEV1 AUC (6-8h). | 6 to 8 hours | 
| FVC AUC0-4 h | Change From Baseline in Forced Vital Capacity (FVC) AUC (0-4h). | 4 hours | 
| FVC AUC4-6 h | Change From Baseline in FVC AUC (4-6h). | 4 to 6 hours | 
| FVC AUC6-8 sa | Change From Baseline in FVC AUC (6-8h). | 6 to 8 hours | 
| FVC AUC0-8 sa | Change From Baseline in FVC AUC (0-8h). | 8 hours | 
| Change From Baseline in FEV1 and FVC within the first 15 minutes after dosing | Spirometric measurements will be performed pre-treatment and 5 min, 15 min, 30 min, 45 min and 1 h, 2 h, 3 h, 4 h, 5 h, 6h, 7h, 8h after drug administration. The measurements at the time points related to the outcome will be evaluated. | Baseline, 15 minutes post-dose at treatment day. | 
| Mean Maximum Change From Baseline in FEV1 and FVC within the first 2 hours after dosing | Spirometric measurements will be performed pre-treatment and 5 min, 15 min, 30 min, 45 min and 1 h, 2 h, 3 h, 4 h, 5 h, 6h, 7h, 8h after drug administration. The measurements at the time points related to the outcome will be evaluated. | Baseline, 2 hours post-dose at treatment day | 
| Mean Maximum Change From Baseline in FEV1 and FVC over a period of 8 hours | Spirometric measurements will be performed pre-treatment and 5 min, 15 min, 30 min, 45 min and 1 h, 2 h, 3 h, 4 h, 5 h, 6h, 7h, 8h after drug administration. | Baseline, 0 to 8 hours post-dose at treatment day | 
| The Time to Onset of Bronchodilator Response | Bronchodilator response is defined as 100 mL improvement in FEV1. | Baseline, 0 to 8 hours post-dose at treatment day | 
| Evaluation of Safety | Number of participants with Adverse Events, with abnormal physical examinations, abnormal laboratory test results and abnormal ECGs | Baseline, 0 to 24 hours post-dose |