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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.
Treatments are described as follows:
Treatment A: Multiple oral YPL-001 80 mg doses (1 x 80 mg tablet + 1 x 1 YPL-001 80 mg matching placebo tablet) will be administered approximately every 12 hours under fasting conditions for 55 consecutive days. Only the morning dose will be administered on Day 56.
Treatment B: Multiple oral YPL-001 160 mg doses (2 x 80 mg tablets) will be administered approximately every 12 hours under fasting conditions for 55 consecutive days. Only the morning dose will be administered on Day 56.
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. Only the morning dose will be administered on Day 56. In all treatments, one tiotropium (Spiriva® HandiHaler®) 18 μg capsule will also be administered QD every morning prior to study drugs administration. Albuterol will be administered on an as needed basis. Each dose of Treatments A, B and C will be administered orally with approximately 240 mL of water.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Experimental | 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. |
|
| Treatment B | Experimental | 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. |
|
| Treatment C | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| YPL-001 80 mg | Drug | twice daily [BID] |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events | 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. | Up to Day 56 |
| Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | 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. | Up to Day 56 |
| Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity. | Up to Day 56 |
| Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity. | Up to Day 56 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | 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. | Baseline (Screen) to Day 55 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gerard J Criner, MD | Temple University | Principal Investigator |
| Mark T Dransfield, MD | The Kirklin Clinic of UAB Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UAB Lung Health Center | Birmingham | Alabama | 35249 | United States | ||
| Florida Pulmonary Research Institute, LLC |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36670877 | Derived | Lee KH, Woo J, Kim J, Lee CH, Yoo CG. YPL-001 Shows Various Beneficial Effects against Cigarette Smoke Extract-Induced Emphysema Formation: Anti-Inflammatory, Anti-Oxidative, and Anti-Apoptotic Effects. Antioxidants (Basel). 2022 Dec 22;12(1):15. doi: 10.3390/antiox12010015. | |
| 29496167 | Derived | Lee SU, Lee S, Ro H, Choi JH, Ryu HW, Kim MO, Yuk HJ, Lee J, Hong ST, Oh SR. Piscroside C inhibits TNF-alpha/NF-kappaB pathway by the suppression of PKCdelta activity for TNF-RSC formation in human airway epithelial cells. Phytomedicine. 2018 Feb 1;40:148-157. doi: 10.1016/j.phymed.2018.01.012. Epub 2018 Jan 31. |
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| ID | Title | Description |
|---|---|---|
| FG000 | YPL-001 Low Dose | Active arm including patients who receive the YPL-001 low dose. YPL-001 low dose: twice daily [BID] |
| FG001 | YPL-001 High Dose | Active arm including patients who receive the YPL-001 high dose, YPL-001 high dose: twice daily [BID] |
| FG002 | Placebo | Control arm including patients who receive the placebo drug. Placebo: twice daily [BID] |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment A | Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM |
| BG001 | Treatment B | Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events | 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. | All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Safety data for all discontinued patients included in this set for the time points for which their data are available. | Posted | Count of Participants | Participants | Up to Day 56 |
|
56 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A | Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Exacerbation of COPD | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry eye | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director of Clinical Trials | Yungjin Pharm. Co., Ltd. | 82-2-2041-8318 | mhlee2017@yungjin.co.kr |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 8, 2016 | Feb 2, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 20, 2017 | Feb 2, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| YPL-001 160 mg | Drug | twice daily [BID] |
|
|
| Placebo | Drug | twice daily [BID] |
|
| Baseline to Day 55 |
| Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 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
Symptom score catecorizes normal(0-0.5), mild(1-1.5), moderate(2-2.5), severe(3-3.5) | Baseline to Day 55 |
| Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) | 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. | Baseline to Day 55 |
| Change From Baseline of Calculated Score From Duke Activity Status Index (DASI) | 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. | Baseline to Day 55 |
| Change From Baseline in Inspiratory Capacity (IC) | 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. | Baseline (Screening) to Day 55 |
| Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio | 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). | Baseline to Day 55 |
| Transition Dyspnea Index (TDI) Focal Score | 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). | Baseline to Day 55 |
| Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) | 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). | Baseline to Day 55 |
| Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | 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. | Baseline (Day -1) and Day 55 |
| Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | 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). | Baseline (Day -1) and Day 55 |
| Change in Percentage of Total Cells in Blood | 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). | Baseline to Day 55 |
| Change in Concentrations of Inflammatory Marker in Plasma/Blood | 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. | Baseline to Day 55 |
| Number of Participants With COPD Exacerbation | 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. | Baseline to Day 56 |
| Change From Baseline in Forced Vital Capacity (FVC) | 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. | Baseline (Screen) to Day 55 |
| Winter Park |
| Florida |
| 32789 |
| United States |
| Aventiv Research Inc. | Columbus | Ohio | 43213 | United States |
| Temple Lung Center, Temple University Hospital | Philadelphia | Pennsylvania | 191140 | United States |
| 28011397 | Derived | Ryu HW, Lee SU, Lee S, Song HH, Son TH, Kim YU, Yuk HJ, Ro H, Lee CK, Hong ST, Oh SR. 3-Methoxy-catalposide inhibits inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages. Cytokine. 2017 Mar;91:57-64. doi: 10.1016/j.cyto.2016.12.006. Epub 2016 Dec 21. |
| 26318254 | Derived | Lee SU, Sung MH, Ryu HW, Lee J, Kim HS, In HJ, Ahn KS, Lee HJ, Lee HK, Shin DH, Lee Y, Hong ST, Oh SR. Verproside inhibits TNF-alpha-induced MUC5AC expression through suppression of the TNF-alpha/NF-kappaB pathway in human airway epithelial cells. Cytokine. 2016 Jan;77:168-75. doi: 10.1016/j.cyto.2015.08.262. Epub 2015 Aug 28. |
| Withdrawal by Subject |
|
| BG002 | Treatment C | Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body mass index | Mean | Standard Deviation | kg/m² |
|
| Treatment B |
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM |
| OG002 | Treatment C | Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM |
|
|
| Primary | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | 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. | All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Safety data for all discontinued patients included in this set for the time points for which their data are available. | Posted | Number | Adverse events | Up to Day 56 |
|
|
|
| Primary | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity. | All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Safety data for all discontinued patients included in this set for the time points for which their data are available. | Posted | Number | participants | Up to Day 56 |
|
|
|
| Primary | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity. | All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Safety data for all discontinued patients included in this set for the time points for which their data are available. | Posted | Number | Adverse events | Up to Day 56 |
|
|
|
| Secondary | Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily | 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. | Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug | Posted | Mean | Standard Deviation | L/min | Baseline to Day 55 |
|
|
|
| Secondary | Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | 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
Symptom score catecorizes normal(0-0.5), mild(1-1.5), moderate(2-2.5), severe(3-3.5) | All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Symptom monitoring data for all discontinued patients were included in this set for the time points for which their data are available. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Day 55 |
|
|
|
| Secondary | Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) | 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. | All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Symptom monitoring data for all discontinued patients were included in this set for the time points for which their data are available. | Posted | Mean | Standard Deviation | units on a scale | Baseline to Day 55 |
|
|
|
| Secondary | Change From Baseline of Calculated Score From Duke Activity Status Index (DASI) | 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. | All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Symptom monitoring data for all discontinued patients included in this set for the time points for which their data are available. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Day 55 |
|
|
|
| Other Pre-specified | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | 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. | Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug | Posted | Mean | Standard Deviation | L | Baseline (Screen) to Day 55 |
|
|
|
| Other Pre-specified | Change From Baseline in Inspiratory Capacity (IC) | 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. | Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug | Posted | Mean | Standard Deviation | L | Baseline (Screening) to Day 55 |
|
|
|
| Other Pre-specified | Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio | 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). | Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug | Posted | Mean | Standard Deviation | ratio | Baseline to Day 55 |
|
|
|
| Other Pre-specified | Transition Dyspnea Index (TDI) Focal Score | 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). | Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug | Posted | Mean | Standard Deviation | units on a scale | Baseline to Day 55 |
|
|
|
| Other Pre-specified | Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) | 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). | Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug | Posted | Mean | Standard Deviation | units on a scale | Baseline to Day 55 |
|
|
|
| Other Pre-specified | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | 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. | All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement. | Posted | Mean | Standard Deviation | percent change from baseline | Baseline (Day -1) and Day 55 |
|
|
|
| Other Pre-specified | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | 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). | All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement. | Posted | Mean | Standard Deviation | % change from baseline | Baseline (Day -1) and Day 55 |
|
|
|
| Other Pre-specified | Change in Percentage of Total Cells in Blood | 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). | All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement. | Posted | Mean | Standard Deviation | % change from baseline | Baseline to Day 55 |
|
|
|
| Other Pre-specified | Change in Concentrations of Inflammatory Marker in Plasma/Blood | 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. | All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement. | Posted | Mean | Standard Deviation | % change from baseline | Baseline to Day 55 |
|
|
|
| Other Pre-specified | Number of Participants With COPD Exacerbation | 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. | Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug | Posted | Count of Participants | Participants | Baseline to Day 56 |
|
|
|
| Other Pre-specified | Change From Baseline in Forced Vital Capacity (FVC) | 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. | Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug | Posted | Mean | Standard Deviation | L | Baseline (Screen) to Day 55 |
|
|
|
| 20 |
| 0 |
| 20 |
| 10 |
| 20 |
| EG001 | Treatment B | Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 | 0 | 21 | 0 | 21 | 8 | 21 |
| EG002 | Treatment C | Multiple oral doses of placebo BID on Days 1 - 55 | 0 | 20 | 1 | 20 | 14 | 20 |
| Eye irritation | Eye disorders | MedDRA (18.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Large intestine polyp | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Epididymitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Subcutaneous abscess | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Chest injury | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
|
| Skeletal injury | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
|
| Large intestinal polypectomy | Surgical and medical procedures | MedDRA (18.0) | Systematic Assessment |
|
| Tooth extraction | Surgical and medical procedures | MedDRA (18.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
|
Not provided
Not provided
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|---|
|
| Gastrointestinal disorders |
|
| Infections and infestations |
|
| Injury, poisoning and procedural complications |
|
| Metabolism and nutrition disorders |
|
| Musculoskeletal and connective tissue disorders |
|
| Nervous system disorders |
|
| Respiratory, thoracic and mediastinal disorders |
|
| Skin and subcutaneous tissue disorders |
|
| Surgical and medical procedures |
|
| Vascular disorders |
|
|
| Severity: Moderate |
|
| Severity: Severe |
|
| Relationship to Drug: Unrelated |
|
| Relationship to Drug: Unlikely |
|
| Relationship to Drug: Possible |
|
| Relationship to Drug: Probable |
|
| Relationship to Drug: Definite |
|
|
| Severity: Moderate |
|
| Severity: Severe |
|
| Relationship to Drug: Unrelated |
|
| Relationship to Drug: Unlikely |
|
| Relationship to Drug: Possible |
|
| Relationship to Drug: Probable |
|
| Relationship to Drug: Definite |
|
| Day55 |
|
|
| Day 55 |
|
|
| Day 55 |
|
|
| Eosinohils |
|
|
| Lymphocytes |
|
|
| Macrophages |
|
|
| Neutrophils |
|
|
|
| IL-1ß |
|
| IL-4 |
|
| IL-5 |
|
| IL-6 |
|
| IL-8 |
|
| MCP-1 |
|
| MMP-9 |
|
| MPO |
|
| TNF-a |
|
| Eosinophils |
|
|
| Lymphocytes |
|
|
| Monocytes |
|
|
| Neutrophils |
|
|
| IL-13 |
|
|
| IL-1ß |
|
|
| IL-4 |
|
|
| IL-5 |
|
|
| IL-6 |
|
|
| IL-8 |
|
|
| MCP1 |
|
|
| MMP9 |
|
|
| MPO |
|
|
| TNF-α |
|
|
| CRP |
|
|
| Fibrinogen |
|
|