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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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI
Salbutamol 100 mcg Inhaler (2 inhalations) + Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination via MDI
Sponsored by
Neutec Ar-Ge San ve Tic A.Ş
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD, ipratropium, levosalbutamol, levalbuterol, salbutamol, albuterol, MDI

Eligibility Criteria

40 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Ipratropium/Levosalbutamol

    Salbutamol + Ipratropium

    Arm Description

    Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI

    Salbutamol 100 mcg Inhaler (2 inhalations) + Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination via MDI

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Evaluation of Safety (physical examination, numbers of adverse reactions and abnormal laboratory values or ECG related to treatment)

    Full Information

    First Posted
    June 23, 2020
    Last Updated
    September 3, 2021
    Sponsor
    Neutec Ar-Ge San ve Tic A.Ş
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04446637
    Brief Title
    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
    Official Title
    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).
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2021
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    administrative decision
    Study Start Date
    September 3, 2021 (Anticipated)
    Primary Completion Date
    September 3, 2022 (Anticipated)
    Study Completion Date
    September 3, 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Neutec Ar-Ge San ve Tic A.Ş

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Obstructive Pulmonary Disease
    Keywords
    COPD, ipratropium, levosalbutamol, levalbuterol, salbutamol, albuterol, MDI

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Multicenter, single day, noninferiority study
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ipratropium/Levosalbutamol
    Arm Type
    Experimental
    Arm Description
    Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI
    Arm Title
    Salbutamol + Ipratropium
    Arm Type
    Active Comparator
    Arm Description
    Salbutamol 100 mcg Inhaler (2 inhalations) + Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination via MDI
    Intervention Type
    Drug
    Intervention Name(s)
    Ipratropium/Levosalbutamol 20/50 mcg Fixed Dose Combination (2 inhalations) via pMDI
    Other Intervention Name(s)
    IPRALEV 20 mcg/50 mcg Aerosol Inhalation, Suspension
    Intervention Description
    Ipratropium/Levosalbutamol 20 mcg/50 mcg Aerosol Inhalation, Suspension 2 inhalations in the morning (single day)
    Intervention Type
    Drug
    Intervention Name(s)
    Salbutamol 100 mcg Inhaler (2 inhalations) + Ipratropium 20 mcg Inhalation Aerosol (2 inhalations) Free Combination via MDI
    Other Intervention Name(s)
    VENTOLİN İnhaler 100 mcg + ATROVENT N MDI 0,02 mg/dose
    Intervention Description
    Salbutamol 100 mcg Inhaler, 2 inhalations + Ipratropium 20 mcg Inhalation Aerosol,2 inhalations in the morning (single day).
    Primary Outcome Measure Information:
    Title
    FEV1 AUC (0-8h)
    Description
    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.
    Time Frame
    Baseline, 0 to 8 hours post-dose at treatment day
    Secondary Outcome Measure Information:
    Title
    FEV1 AUC (0-4h)
    Description
    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.
    Time Frame
    Baseline, 0 to 4 hours post-dose at treatment day
    Title
    FEV1 AUC (4-6h)
    Description
    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.
    Time Frame
    Baseline, 4 to 6 hours post-dose at treatment day
    Title
    FEV1 AUC (6-8h)
    Description
    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.
    Time Frame
    Baseline, 6 to 8 hours post-dose at treatment day
    Title
    FVC AUC (0-4h)
    Description
    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.
    Time Frame
    Baseline, 0 to 4 hours post-dose at treatment day
    Title
    FVC AUC (4-6h)
    Description
    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.
    Time Frame
    Baseline, 4 to 6 hours post-dose at treatment day
    Title
    FVC AUC (6-8h)
    Description
    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.
    Time Frame
    Baseline, 6 to 8 hours post-dose at treatment day
    Title
    FVC AUC (0-8h)
    Description
    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.
    Time Frame
    Baseline, 0 to 8 hours post-dose at treatment day
    Title
    Change From Baseline in FEV1 and FVC within the first 15 minutes after dosing
    Description
    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.
    Time Frame
    Baseline, 0 to 15 minutes post-dose at treatment day
    Title
    Mean Maximum Change From Baseline in FEV1 and FVC within the first 2 hours after dosing
    Description
    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.
    Time Frame
    Baseline, 0 to 2 hours post-dose at treatment day
    Title
    Mean Maximum Change From Baseline in FEV1 and FVC over a period of 8 hours
    Description
    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.
    Time Frame
    Baseline, 0 to 8 hours post-dose at treatment day
    Title
    The Time to Onset of Bronchodilator Response
    Description
    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.
    Time Frame
    Baseline, 0 to 8 hours post-dose at treatment day
    Title
    The Time to Maximum Effect
    Description
    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.
    Time Frame
    Baseline, 0 to 8 hours post-dose at treatment day
    Title
    Duration of Bronchodilator Response
    Description
    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.
    Time Frame
    Baseline, 0 to 8 hours post-dose at treatment day
    Title
    Evaluation of Safety (physical examination, numbers of adverse reactions and abnormal laboratory values or ECG related to treatment)
    Time Frame
    Baseline, 0 to 24 hours post-dose

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Maximum Age & Unit of Time
    120 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Ismail Hanta, Professor Doctor
    Organizational Affiliation
    Cukurova University Faculty of Medicine, Chest Diseases Department Adana - Turkey
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Hakan Gunen, Professor Doctor
    Organizational Affiliation
    Sureyyapasa Training and Research Center for Chest Diseases and Thoracic Surgery, Maltepe, Istanbul - Turkey
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    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

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