Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, ipratropium, levosalbutamol, levalbuterol, salbutamol, albuterol, MDI
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.
Interventions
DRUGSalbutamol 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 in the morning (single day).
DRUGIpratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI
Ipratropium/Levosalbutamol 20 mcg/50 mcg Aerosol Inhalation, Suspension 2 inhalations in the morning (single day)
Sponsors
Neutec Ar-Ge San ve Tic A.Ş
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicenter, single day, noninferiority study
Eligibility
Sex/Gender
ALL
Age
40 Years to 120 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 (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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 | — |
| 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. |
Outcome results
None listed