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

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).

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.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: 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

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ipratropium/Levosalbutamol; 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; Ipratropium/Levosalbutamol 20 mcg/50 mcg Aerosol Inhalation, Suspension 2 inhalations in the morning (single day); Other Names: IPRALEV 20 mcg/50 mcg Aerosol Inhalation, Suspension
Active Comparator: Salbutamol + Ipratropium; 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; Salbutamol 100 mcg Inhaler, 2 inhalations + Ipratropium 20 mcg Inhalation Aerosol,2 inhalations in the morning (single day).; Other Names: VENTOLİN İnhaler 100 mcg + ATROVENT N MDI 0,02 mg/dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Neutec Ar-Ge San ve Tic A.Ş
• Investigators: Principal Investigator: Ismail Hanta, Professor Doctor, Cukurova University Faculty of Medicine, Chest Diseases Department Adana - Turkey; Principal Investigator: Hakan Gunen, Professor Doctor, Sureyyapasa Training and Research Center for Chest Diseases and Thoracic Surgery, Maltepe, Istanbul - Turkey

Study record dates

Study Major Dates

• Study Start (Anticipated): September 3, 2021
• Primary Completion (Anticipated): September 3, 2022
• Study Completion (Anticipated): September 3, 2022

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 25, 2020

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 3, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: COPD, ipratropium, levosalbutamol, levalbuterol, salbutamol, albuterol, MDI
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Ipratropium
• Other Study ID Numbers: NEU-01.19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No