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
- Conditions
- Chronic Obstructive Pulmonary Disease
- Interventions
- Drug: Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI
- Registration Number
- NCT04446637
- Lead Sponsor
- Neutec Ar-Ge San ve Tic A.Ş
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ipratropium/Levosalbutamol Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI Salbutamol + Ipratropium Salbutamol 100 mcg Inhaler (2 inhalations) + Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination via MDI Salbutamol 100 mcg Inhaler (2 inhalations) + Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination via MDI
- Primary Outcome Measures
Name Time Method FEV1 AUC (0-8h) Baseline, 0 to 8 hours post-dose at treatment day 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.
- Secondary Outcome Measures
Name Time Method FVC AUC (6-8h) Baseline, 6 to 8 hours post-dose at treatment day 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.
The Time to Maximum Effect Baseline, 0 to 8 hours post-dose at treatment day 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.
Duration of Bronchodilator Response Baseline, 0 to 8 hours post-dose at treatment day 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.
FEV1 AUC (0-4h) Baseline, 0 to 4 hours post-dose at treatment day 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.
FEV1 AUC (4-6h) Baseline, 4 to 6 hours post-dose at treatment day 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.
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 FEV1 AUC (6-8h) Baseline, 6 to 8 hours post-dose at treatment day 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.
FVC AUC (0-4h) Baseline, 0 to 4 hours post-dose at treatment day 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.
FVC AUC (4-6h) Baseline, 4 to 6 hours post-dose at treatment day 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.
FVC AUC (0-8h) Baseline, 0 to 8 hours post-dose at treatment day 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.
Change From Baseline in FEV1 and FVC within the first 15 minutes after dosing Baseline, 0 to 15 minutes post-dose at treatment day 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.
Mean Maximum Change From Baseline in FEV1 and FVC within the first 2 hours after dosing Baseline, 0 to 2 hours post-dose at treatment day 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.
Mean Maximum Change From Baseline in FEV1 and FVC over a period of 8 hours Baseline, 0 to 8 hours post-dose at treatment day 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 Time to Onset of Bronchodilator Response Baseline, 0 to 8 hours post-dose at treatment day 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.