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A Phase 2a Study to Assess Safety, Daily Symptoms, Pharmacokinetics (PK), and Biomarkers of YPL-001 in Chronic Obstructive Pulmonary Disease (COPD) Patients

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ClinicalTrials.gov Identifier: NCT02272634
Recruitment Status : Completed
First Posted : October 23, 2014
Results First Posted : June 25, 2021
Last Update Posted : June 25, 2021
Sponsor:
Information provided by (Responsible Party):
Yungjin Pharm. Co., Ltd.

Brief Summary:
This is a Phase 2a, proof-of-concept, multicenter, randomized, double-blind, double dummy, 3-treatment, parallel study, with low and high YPL 001 doses (low dose and high dose twice daily [BID]) and a placebo control in moderate to severe Chronic Obstructive Pulmonary Disease (COPD) patients.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: YPL-001 80 mg Drug: YPL-001 160 mg Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo Controlled, Multicenter Phase 2a Study to Assess Safety, Daily Respiratory Symptoms, Pharmacokinetics, and Biomarker Variations After Administration of Either YPL-001, or Placebo in Patients With Moderate-to-Severe Chronic Obstructive Pulmonary Disease
Actual Study Start Date : June 4, 2015
Actual Primary Completion Date : November 8, 2017
Actual Study Completion Date : November 8, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases

Arm Intervention/treatment
Experimental: Treatment A
Multiple oral YPL-001 80 mg doses (1 x 80 mg tablet + 1 x 1 YPL-001 80 mg matching placebo tablet) are administered approximately every 12 hours under fasting conditions for 55 consecutive days.
Drug: YPL-001 80 mg
twice daily [BID]

Experimental: Treatment B
Multiple oral YPL-001 160 mg doses (2 x 80 mg tablets) are administered approximately every 12 hours under fasting conditions for 55 consecutive days.
Drug: YPL-001 160 mg
twice daily [BID]

Placebo Comparator: Treatment C
Multiple oral matching placebo (2 x 1 YPL-001 80 mg matching placebo tablets) will be administered approximately every 12 hours under fasting conditions for 55 consecutive days.
Drug: Placebo
twice daily [BID]




Primary Outcome Measures :
  1. Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events [ Time Frame: Up to Day 56 ]
    A TEAE was defined as an AE that was starting or worsening at the time of or after study drug administration. All AEs collected by the clinics and recorded in the CRF were captured in the database and were listed in by-patient data listings.

  2. Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events [ Time Frame: Up to Day 56 ]
    A TEAE was defined as an AE that was starting or worsening at the time of or after study drug administration. All AEs collected by the clinics and recorded in the CRF were captured in the database and were listed in by-patient data listings.

  3. Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events [ Time Frame: Up to Day 56 ]
    When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity.

  4. Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events [ Time Frame: Up to Day 56 ]
    When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity.


Secondary Outcome Measures :
  1. Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily [ Time Frame: Baseline to Day 55 ]
    The PEF assessments are made daily prior to each dose from Day 1 of the Run-in Period to Day 56 of the Treatment Period. Three measurements were made at each time point using a hand held PEF meter. Readings not performed in the clinical research unit (CRU) were recorded in the patient e-diary. All PEF assessments were performed before administration of a bronchodilator where possible. Baseline is Day 1 predose measurement.

  2. Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation [ Time Frame: Baseline to Day 55 ]

    Patient is asked to record the major (sputum quality, color, consistency) and minor (cough, wheeze, sore throat, nasal congestion, discharge, and body temperature above 100°F) symptoms of COPD exacerbation via the e-diary before each dosing. Baseline is Day 1 predose measurement

    1. Breathlessness(Dyspnea) Screen: 0(None)-10(Extreme): 0: better condition, 10: worse condition
    2. Sputum Quantity Screen: None(better)-greater than 1/4 cup(worse)
    3. Sputum Color Screen: White(better)-Brown(condition)
    4. Sputum Consistency Screen: Watery(better)-Thick(worse)
    5. Peak Flow Measurement Screen: 60(better)-800(worse)
    6. Symptoms Screen: (Temperature over 100F / Cough/Wheeze/Sore Throat/ Nasal Congestion)
    7. Nasal Discharge Screen(Yes/No) * quantitative data were summarized including sample size, arithmetic mean, standard deviation, CV, min and max.

    Symptom score catecorizes normal(0-0.5), mild(1-1.5), moderate(2-2.5), severe(3-3.5)


  3. Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) [ Time Frame: Baseline to Day 55 ]
    Severity level of patient's dyspnea is accessed via the modified Borg dyspnea scale programmed within the e-diary. The modified Borg dyspnea scale is a self-administered categorical scale with a score from 0 to 10, where 0 (as a measure of dyspnea) corresponds to the sensation of normal breathing (absence of dyspnea) and 10 corresponds to the patient's maximum possible sensation of dyspnea.

  4. Change From Baseline of Calculated Score From Duke Activity Status Index (DASI) [ Time Frame: Baseline to Day 55 ]

    Patient's functional capacity and activity status were accessed via the DASI programmed within the e-diary. DASI is a self-administered 12-item questionnaire that assesses daily activities such as personal care, ambulation, household tasks, sexual function and recreation with respective metabolic costs. Each item has a specific weight based on the metabolic cost. The final score ranges between 0 and 58.2 points.

    The higher score shows the better the functional capacity.



Other Outcome Measures:
  1. Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline (Screen) to Day 55 ]
    Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 is measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. A positive change from baseline in FEV1 indicates improvement in lung function.

  2. Change From Baseline in Inspiratory Capacity (IC) [ Time Frame: Baseline (Screening) to Day 55 ]
    Inspiratory capacity (IC) is the maximum volume of air that can be inhaled into the lungs from the normal resting position after breathing out normally. IC is measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation.

  3. Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio [ Time Frame: Baseline to Day 55 ]
    The ratio is calculated as the amount of air expelled from the lungs in one second after a full inspiration (FEV1) divided by the volume of air that can forcibly be blown out after a full inspiration (FVC).

  4. Transition Dyspnea Index (TDI) Focal Score [ Time Frame: Baseline to Day 55 ]
    Dyspnea at baseline (Day -1) will be assessed with the Baseline Dyspnea Index (BDI). This instrument has 3 domains (functional impairment, magnitude of task and magnitude of effort) with the values added for a combined focal score. Functional impairment determines the impact of breathlessness on the ability to carry out activities; magnitude of task determines the type of task that causes breathlessness, magnitude of effort establishes the level of effort that results in breathlessness. The BDI scores range from 0 (very severe impairment) to 4 (no impairment) for each domain with the baseline focal score consisting of the sum of each domain (0 to 12). Dyspnea throughout the study will be performed at the time points. The change from baseline is measured by the Transition Dyspnea Index (TDI) score which ranges from -3 (major deterioration) to +3 (major improvement) for each domain with the TDI focal score consisting in the sum of each domain (-9 to +9).

  5. Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) [ Time Frame: Baseline to Day 55 ]
    The chronic obstructive pulmonary disease assessment test (CAT) is a short and simple questionnaire of 8 items completed by patients to be performed at the time points. Scores for each of the 8 items are summed to give a single, final score ranging from 0 (no impact on daily activities) to 40 (very high impact on daily activity).

  6. Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) [ Time Frame: Baseline (Day -1) and Day 55 ]
    The bronchoalveolar lavage (BAL) samples were collected at baseline and again at the completion of the study for pharmacodynamics (PD) assessments of biomarkers. BAL samples are at analyzed for total cell count (cells/mL) of white blood cell, macrophages, lymphocytes, neutrophils, and eosinophils as a percentage of total cells.

  7. Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) [ Time Frame: Baseline (Day -1) and Day 55 ]
    The bronchoalveolar lavage (BAL) samples are collected at baseline and again at the completion of the study for pharmacodynamics (PD) assessments of biomarkers. BAL samples are analyzed for concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-13, Myeloperoxidase (MPO), neutrophil elastase (ELA2), monocyte chemotactic protein-1 (MCP-1), myeloperoxidase(MPO), and matrix metalloproteinase-9 (MMP-9).

  8. Change in Percentage of Total Cells in Blood [ Time Frame: Baseline to Day 55 ]
    The blood samples are collected at the the time points of the study for pharmacodynamics (PD) assessments of biomarkers. The blood samples are analyzed for inflammatory markers (total and differential cell counts as absolute and percentage for neutrophils, macrophages, eosinophils and lymphocytes).

  9. Change in Concentrations of Inflammatory Marker in Plasma/Blood [ Time Frame: Baseline to Day 55 ]
    The blood samples are collected at the the time points of the study for pharmacodynamics (PD) assessments of biomarkers. The blood samples are analyzed for concentrations of C-reactive protein (CRP), fibrinogen, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-13, MCP-1, and MMP-9. Baseline is Day 1 predose measurement.

  10. Number of Participants With COPD Exacerbation [ Time Frame: Baseline to Day 56 ]
    Number of COPD exacerbation during 8-week treatment. COPD exacerbations are defined as a new onset or worsening of at least one respiratory symptom (i.e. dyspnea, cough, sputum purulence or volume, or wheeze) present for at least 3 consecutive days, documented change or increase in COPD-related treatment due to worsening symptoms or documented COPD-related hospitalizations or emergency room visits.

  11. Change From Baseline in Forced Vital Capacity (FVC) [ Time Frame: Baseline (Screen) to Day 55 ]
    Forced vital capacity (FVC) is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC is measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. A positive change from baseline in FVC indicates improvement in lung function.



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Ages Eligible for Study:   30 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult males and/or females, 30 to 85 years of age (inclusive).
  • History of COPD for at least 12 months prior to screening.
  • Diagnosed with COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD for at least 12 months prior to screening.
  • Classified as moderate to severe COPD based on the current severity classification GOLD Stage 2-3 disease in terms of post-bronchodilator spirometry at screening
  • etc.

Exclusion Criteria:

  • History of life-threatening COPD including respiratory arrest, intensive care unit admission and/or requiring intubation.
  • History of more than 2 hospitalizations for COPD within 12 months prior to screening.
  • Presentation of an acute exacerbation of COPD that will be associated with increase sputum volume or change in sputum color within 4 weeks before Day 1 of the Run-in Period.
  • Evidence of pulmonary heart disease, or clinically significant pulmonary hypertension.
  • etc.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02272634


Locations
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United States, Alabama
UAB Lung Health Center
Birmingham, Alabama, United States, 35249
United States, Florida
Florida Pulmonary Research Institute, LLC
Winter Park, Florida, United States, 32789
United States, Ohio
Aventiv Research Inc.
Columbus, Ohio, United States, 43213
United States, Pennsylvania
Temple Lung Center, Temple University Hospital
Philadelphia, Pennsylvania, United States, 191140
Sponsors and Collaborators
Yungjin Pharm. Co., Ltd.
Investigators
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Principal Investigator: Gerard J Criner, MD Temple University
Principal Investigator: Mark T Dransfield, MD The Kirklin Clinic of UAB Hospital
  Study Documents (Full-Text)

Documents provided by Yungjin Pharm. Co., Ltd.:
Study Protocol  [PDF] June 8, 2016
Statistical Analysis Plan  [PDF] March 20, 2017

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Yungjin Pharm. Co., Ltd.
ClinicalTrials.gov Identifier: NCT02272634    
Other Study ID Numbers: YPL-001_YJP-130403
First Posted: October 23, 2014    Key Record Dates
Results First Posted: June 25, 2021
Last Update Posted: June 25, 2021
Last Verified: June 2021
Keywords provided by Yungjin Pharm. Co., Ltd.:
COPD
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases