Acute Bronchodilator Effects of Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination vs Salbutamol 100 mcg Inhaler Plus Ipratropium 20 mcg Inhalation Aerosol Free Combination in Patients With Stable COPD

Study Overview
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Brief Summary
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The purpose of this study is to compare acute bronchodilator effects of Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI and Salbutamol 100 mcg Inhaler (2 inhalations) plus Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination in Patients with stable moderate-severe-very severe COPD.

Official Title
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Comparison of Acute Bronchodilator Effects of Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination Delivered Via pMDI and Salbutamol 100 mcg Inhaler Plus Ipratropium 20 mcg Inhalation Aerosol in Patients With Stable Moderate-Severe-Very Severe Chronic Obstructive Pulmonary Disease (COPD).

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI
* Drug: Salbutamol 100 mcg Inhaler (2 inhalations) + Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination via MDI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male patients aged ≥40 years diagnosed with symptomathic stable moderate-severe-very severe COPD: post-bronchodilator FEV1/FVC <70% predicted and a post-bronchodilator FEV1 <80% predicted at screen visit. Group B COPD CAT: ≥10 or mMRC: ≥ 2 Exacerbation: 0-1 (not leading to hospital admission) Group C COPD CAT: <10 or mMRC: 0-1 Exacerbation: ≥2 (not leading to hospital admission) or ≥1 (leading to hospital admission) Group D COPD CAT: ≥10 or mMRC: ≥ 2 Exacerbation: ≥2 (not leading to hospital admission) or ≥1 (leading to hospital admission) Current or ex-smokers with a smoking history of at least 10 pack-years Patients who have no exacerbation within the last 4 weeks Female patients who use effective contraception Patients who have a capability to communicate with investigator Patients who accept to comply with the protocol Patients who sign written informed consent form Exclusion Criteria: History of hypersensitive to anticholinergics or SABAs History of COPD exacerbation or lower respiratory track infection that required treatment with antibiotic, oral or parenteral corticosteroid within the last 4 weeks 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 Use of oral corticosteroid at unstable dosages (i.e. <6 weeks on a stable dose of prednisone) 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. Initiation of an inhaled steroid or change in dose within <6 weeks prior the screening visit Use of beta-blocker, monoamine oxidase (MAO) inhibitor or tricyclic antidepressant within the last 30 days prior the screening visit Recent (within ≤1 year 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 measure) 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 History of cancer within the last 5 years 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
Maximum Age: 120 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
Interventional Model Description: Multicenter, single day, noninferiority study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipratropium/Levosalbutamol<br>Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI | Drug: Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI<br>* Ipratropium/Levosalbutamol 20 mcg/50 mcg Aerosol Inhalation, Suspension 2 inhalations in the morning (single day)<br>* Other names: IPRALEV 20 mcg/50 mcg Aerosol Inhalation, Suspension;|
| Active Comparator: Salbutamol + Ipratropium<br>Salbutamol 100 mcg Inhaler (2 inhalations) + Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination via MDI | Drug: Salbutamol 100 mcg Inhaler (2 inhalations) + Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination via MDI<br>* Salbutamol 100 mcg Inhaler, 2 inhalations + Ipratropium 20 mcg Inhalation Aerosol,2 inhalations in the morning (single day).<br>* Other names: VENTOLİN İnhaler 100 mcg + ATROVENT N MDI 0,02 mg/dose;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 AUC (0-4h) | Change From Baseline in FEV1 AUC (0-4h). 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 4 hours post-dose at treatment day | 
| FEV1 AUC (4-6h) | Change From Baseline in FEV1 AUC (4-6h). 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, 4 to 6 hours post-dose at treatment day | 
| FEV1 AUC (6-8h) | Change From Baseline in FEV1 AUC (6-8h). 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, 6 to 8 hours post-dose at treatment day | 
| FVC AUC (0-4h) | Change From Baseline in Forced Vital Capacity (FVC) AUC (0-4h). 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 4 hours post-dose at treatment day | 
| FVC AUC (4-6h) | Change From Baseline in FVC AUC (4-6h). 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, 4 to 6 hours post-dose at treatment day | 
| FVC AUC (6-8h) | Change From Baseline in FVC AUC (6-8h). 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, 6 to 8 hours post-dose at treatment day | 
| FVC AUC (0-8h) | Change From Baseline in FVC AUC (0-8h). 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 | 
| 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. | Baseline, 0 to 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. | Baseline, 0 to 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. 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 Maximum Effect | 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 | 
| Duration of Bronchodilator Response | Bronchodilator response is defined as 100 mL improvement in FEV1. 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 | 
| Evaluation of Safety (physical examination, numbers of adverse reactions and abnormal laboratory values or ECG related to treatment) |  | Baseline, 0 to 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, ipratropium, levosalbutamol, levalbuterol, salbutamol, albuterol, MDI