A Phase 2a Study to Assess Safety, Daily Symptoms, PK, and Biomarkers of YPL-001 in COPD Patients

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo Controlled, Multicenter 2a Study to Assess Safety, Daily Respiratory Symptoms, PK, and Biomarker Variations After Administration of Either YPL-001, or Placebo in Patients With Moderate-to-Severe COPD.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02272634
• Other study ID #: YPL-001_YJP-130403
• Status: Completed
• Phase: Phase 2
• Start date: June 4, 2015
• Est. completion date: November 8, 2017

Study information

• Verified date: June 2021
• Source: Yungjin Pharm. Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: November 8, 2017
• Est. primary completion date: November 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• YPL-001 80 mg
twice daily [BID]
• YPL-001 160 mg
twice daily [BID]
• Placebo
twice daily [BID]

Locations

Country	Name	City	State
United States	UAB Lung Health Center	Birmingham	Alabama
United States	Aventiv Research Inc.	Columbus	Ohio
United States	Temple Lung Center, Temple University Hospital	Philadelphia	Pennsylvania
United States	Florida Pulmonary Research Institute, LLC	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Yungjin Pharm. Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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)-1ß, 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
Other	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
Other	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-a, IL-1ß, 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
Other	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
Other	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
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.	Up to Day 56
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.	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.	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.	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.	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; Breathlessness(Dyspnea) Screen: 0(None)-10(Extreme): 0: better condition, 10: worse condition; Sputum Quantity Screen: None(better)-greater than 1/4 cup(worse); Sputum Color Screen: White(better)-Brown(condition); Sputum Consistency Screen: Watery(better)-Thick(worse); Peak Flow Measurement Screen: 60(better)-800(worse); Symptoms Screen: (Temperature over 100F / Cough/Wheeze/Sore Throat/ Nasal Congestion); 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)	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.	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.	Baseline to Day 55