Trial Outcomes & Findings for A Phase 2a Study to Assess Safety, Daily Symptoms, PK, and Biomarkers of YPL-001 in COPD Patients (NCT NCT02272634)

NCT ID: NCT02272634

Last Updated: 2023-07-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

61 participants

Primary outcome timeframe

Up to Day 56

Results posted on

2023-07-14

Participant Flow

Participant milestones

Participant milestones
Measure
YPL-001 Low Dose
Active arm including patients who receive the YPL-001 low dose. YPL-001 low dose: twice daily \[BID\]
YPL-001 High Dose
Active arm including patients who receive the YPL-001 high dose, YPL-001 high dose: twice daily \[BID\]
Placebo
Control arm including patients who receive the placebo drug. Placebo: twice daily \[BID\]
Overall Study
STARTED
20
21
20
Overall Study
COMPLETED
19
20
19
Overall Study
NOT COMPLETED
1
1
1

Reasons for withdrawal

Reasons for withdrawal
Measure
YPL-001 Low Dose
Active arm including patients who receive the YPL-001 low dose. YPL-001 low dose: twice daily \[BID\]
YPL-001 High Dose
Active arm including patients who receive the YPL-001 high dose, YPL-001 high dose: twice daily \[BID\]
Placebo
Control arm including patients who receive the placebo drug. Placebo: twice daily \[BID\]
Overall Study
Adverse Event
1
0
0
Overall Study
Protocol Violation
0
0
1
Overall Study
Withdrawal by Subject
0
1
0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment A
n=20 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Total
n=61 Participants
Total of all reporting groups
Age, Continuous
65.7 years
STANDARD_DEVIATION 8.66 • n=99 Participants
60.4 years
STANDARD_DEVIATION 6.50 • n=107 Participants
61.7 years
STANDARD_DEVIATION 7.95 • n=206 Participants
62.6 years
STANDARD_DEVIATION 7.98 • n=7 Participants
Sex: Female, Male
Female
8 Participants
n=99 Participants
8 Participants
n=107 Participants
9 Participants
n=206 Participants
25 Participants
n=7 Participants
Sex: Female, Male
Male
12 Participants
n=99 Participants
13 Participants
n=107 Participants
11 Participants
n=206 Participants
36 Participants
n=7 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
1 Participants
n=7 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
19 Participants
n=99 Participants
21 Participants
n=107 Participants
20 Participants
n=206 Participants
60 Participants
n=7 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Asian
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Black or African American
5 Participants
n=99 Participants
6 Participants
n=107 Participants
5 Participants
n=206 Participants
16 Participants
n=7 Participants
Race (NIH/OMB)
White
15 Participants
n=99 Participants
15 Participants
n=107 Participants
15 Participants
n=206 Participants
45 Participants
n=7 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Region of Enrollment
United States
20 Participants
n=99 Participants
21 Participants
n=107 Participants
20 Participants
n=206 Participants
61 Participants
n=7 Participants
Body mass index
28.34 kg/m²
STANDARD_DEVIATION 4.759 • n=99 Participants
27.77 kg/m²
STANDARD_DEVIATION 3.838 • n=107 Participants
26.19 kg/m²
STANDARD_DEVIATION 4.711 • n=206 Participants
27.44 kg/m²
STANDARD_DEVIATION 4.465 • n=7 Participants

PRIMARY outcome

Timeframe: Up to Day 56

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=20 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events
Number of Patients With AEs
10 Participants
8 Participants
14 Participants
Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events
Number of Patients Without AEs
10 Participants
13 Participants
6 Participants

PRIMARY outcome

Timeframe: Up to Day 56

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=20 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Musculoskeletal and connective tissue disorders
1 Adverse events
2 Adverse events
0 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Nervous system disorders
0 Adverse events
1 Adverse events
0 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Total Number of AEs
18 Adverse events
14 Adverse events
23 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Eye disorders
1 Adverse events
1 Adverse events
0 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Gastrointestinal disorders
3 Adverse events
1 Adverse events
1 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Infections and infestations
5 Adverse events
3 Adverse events
6 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Injury, poisoning and procedural complications
0 Adverse events
0 Adverse events
2 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Metabolism and nutrition disorders
1 Adverse events
0 Adverse events
0 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Respiratory, thoracic and mediastinal disorders
5 Adverse events
4 Adverse events
13 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Skin and subcutaneous tissue disorders
0 Adverse events
1 Adverse events
1 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Surgical and medical procedures
1 Adverse events
1 Adverse events
0 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
Vascular disorders
1 Adverse events
0 Adverse events
0 Adverse events

PRIMARY outcome

Timeframe: Up to Day 56

Population: 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.

When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity.

Outcome measures

Outcome measures
Measure
Treatment A
n=20 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
Number of Patients With AEs
10 participants
8 participants
14 participants
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
Severity: Mild
3 participants
3 participants
4 participants
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
Severity: Moderate
7 participants
5 participants
9 participants
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
Severity: Severe
0 participants
0 participants
1 participants
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
Relationship to Drug: Unrelated
9 participants
7 participants
14 participants
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
Relationship to Drug: Unlikely
0 participants
1 participants
0 participants
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
Relationship to Drug: Possible
1 participants
0 participants
0 participants
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
Relationship to Drug: Probable
0 participants
0 participants
0 participants
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
Relationship to Drug: Definite
0 participants
0 participants
0 participants

PRIMARY outcome

Timeframe: Up to Day 56

Population: 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.

When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity.

Outcome measures

Outcome measures
Measure
Treatment A
n=20 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
Number of Adverse Events
18 Adverse events
14 Adverse events
23 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
Severity: Mild
9 Adverse events
8 Adverse events
11 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
Severity: Moderate
9 Adverse events
6 Adverse events
11 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
Severity: Severe
0 Adverse events
0 Adverse events
1 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
Relationship to Drug: Unrelated
17 Adverse events
12 Adverse events
23 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
Relationship to Drug: Unlikely
0 Adverse events
2 Adverse events
0 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
Relationship to Drug: Possible
1 Adverse events
0 Adverse events
0 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
Relationship to Drug: Probable
0 Adverse events
0 Adverse events
0 Adverse events
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
Relationship to Drug: Definite
0 Adverse events
0 Adverse events
0 Adverse events

SECONDARY outcome

Timeframe: Baseline to Day 55

Population: 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

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily
Baseline (Day1)
250.0 L/min
Standard Deviation 109.82
254.9 L/min
Standard Deviation 68.61
240.7 L/min
Standard Deviation 68.21
Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily
Day55
282.8 L/min
Standard Deviation 123.61
277.9 L/min
Standard Deviation 92.08
247.6 L/min
Standard Deviation 96.17

SECONDARY outcome

Timeframe: Baseline to Day 55

Population: 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.

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)

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Baseline (Day 1)
0.63 score on a scale
Standard Deviation 0.812
0.17 score on a scale
Standard Deviation 0.297
0.47 score on a scale
Standard Deviation 0.757
Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Day 55
0.26 score on a scale
Standard Deviation 0.504
0.18 score on a scale
Standard Deviation 0.351
0.50 score on a scale
Standard Deviation 0.876

SECONDARY outcome

Timeframe: Baseline to Day 55

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale)
Day 55
3.76 units on a scale
Standard Deviation 2.463
3.88 units on a scale
Standard Deviation 2.147
3.31 units on a scale
Standard Deviation 2.323
Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale)
Baseline (Day 1)
3.88 units on a scale
Standard Deviation 1.996
4.05 units on a scale
Standard Deviation 1.746
3.18 units on a scale
Standard Deviation 2.512

SECONDARY outcome

Timeframe: Baseline to Day 55

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change From Baseline of Calculated Score From Duke Activity Status Index (DASI)
-0.267 score on a scale
Standard Deviation 3.7696
-2.844 score on a scale
Standard Deviation 9.8016
1.137 score on a scale
Standard Deviation 4.8336

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Screen) to Day 55

Population: 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

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
-0.088 L
Standard Deviation 0.2721
-0.002 L
Standard Deviation 0.1974
0.011 L
Standard Deviation 0.1533

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Screening) to Day 55

Population: 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

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change From Baseline in Inspiratory Capacity (IC)
-0.158 L
Standard Deviation 0.3148
-0.097 L
Standard Deviation 0.4357
-0.304 L
Standard Deviation 0.4709

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 55

Population: 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

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).

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio
-1.8 ratio
Standard Deviation 6.21
-0.2 ratio
Standard Deviation 4.63
2.0 ratio
Standard Deviation 4.98

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 55

Population: 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

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).

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Transition Dyspnea Index (TDI) Focal Score
2.2 units on a scale
Standard Deviation 2.68
1.1 units on a scale
Standard Deviation 2.75
2.9 units on a scale
Standard Deviation 2.84

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 55

Population: 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

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).

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT)
-1.2 units on a scale
Standard Deviation 6.14
-1.3 units on a scale
Standard Deviation 5.11
0.0 units on a scale
Standard Deviation 7.38

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day -1) and Day 55

Population: All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement.

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=20 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL)
Macrophages
45.9 percent change from baseline
Standard Deviation 136.88
9.3 percent change from baseline
Standard Deviation 55.48
59.8 percent change from baseline
Standard Deviation 124.05
Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL)
WBC
5.2 percent change from baseline
Standard Deviation 23.16
-2.3 percent change from baseline
Standard Deviation 22.87
-5.6 percent change from baseline
Standard Deviation 21.16
Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL)
Eosinohils
-50.8 percent change from baseline
Standard Deviation 49.25
38.3 percent change from baseline
Standard Deviation 150.97
61.2 percent change from baseline
Standard Deviation 261.73
Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL)
Lymphocytes
37.8 percent change from baseline
Standard Deviation 111.26
2.7 percent change from baseline
Standard Deviation 75.89
19.4 percent change from baseline
Standard Deviation 121.45
Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL)
Neutrophils
57.0 percent change from baseline
Standard Deviation 152.70
83.5 percent change from baseline
Standard Deviation 252.98
1.1 percent change from baseline
Standard Deviation 106.19

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day -1) and Day 55

Population: All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement.

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).

Outcome measures

Outcome measures
Measure
Treatment A
n=17 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=20 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=18 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
ELA2(neutrophil elastage)
46.36 % change from baseline
Standard Deviation 154.476
714.18 % change from baseline
Standard Deviation 1864.367
155.57 % change from baseline
Standard Deviation 523.538
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
IL-1ß
79.65 % change from baseline
Standard Deviation 216.674
223.62 % change from baseline
Standard Deviation 618.896
45.43 % change from baseline
Standard Deviation 207.504
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
MCP-1
90.05 % change from baseline
Standard Deviation 224.213
155.50 % change from baseline
Standard Deviation 601.606
252.95 % change from baseline
Standard Deviation 816.196
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
TNF-a
14.04 % change from baseline
Standard Deviation 114.456
268.19 % change from baseline
Standard Deviation 863.815
124.20 % change from baseline
Standard Deviation 266.423
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
IL-13
34.47 % change from baseline
Standard Deviation 187.126
321.42 % change from baseline
Standard Deviation 1168.485
160.25 % change from baseline
Standard Deviation 243.317
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
IL-4
11.12 % change from baseline
Standard Deviation 101.995
121.13 % change from baseline
Standard Deviation 258.496
155.36 % change from baseline
Standard Deviation 276.287
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
IL-5
49.97 % change from baseline
Standard Deviation 161.255
220.88 % change from baseline
Standard Deviation 523.979
213.86 % change from baseline
Standard Deviation 341.157
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
IL-6
-7.41 % change from baseline
Standard Deviation 79.289
130.15 % change from baseline
Standard Deviation 354.531
53.48 % change from baseline
Standard Deviation 153.791
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
IL-8
50.61 % change from baseline
Standard Deviation 178.116
173.57 % change from baseline
Standard Deviation 600.987
45.40 % change from baseline
Standard Deviation 222.303
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
MMP-9
28.38 % change from baseline
Standard Deviation 201.899
565.88 % change from baseline
Standard Deviation 2067.142
43.31 % change from baseline
Standard Deviation 242.912
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
MPO
64.14 % change from baseline
Standard Deviation 243.237
275.50 % change from baseline
Standard Deviation 693.932
62.14 % change from baseline
Standard Deviation 199.545

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 55

Population: All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement.

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).

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change in Percentage of Total Cells in Blood
WBC
5.229 % change from baseline
Standard Deviation 23.1568
-2.289 % change from baseline
Standard Deviation 22.8687
-5.572 % change from baseline
Standard Deviation 21.1569
Change in Percentage of Total Cells in Blood
Eosinophils
7.61728 % change from baseline
Standard Deviation 78.203389
20.06903 % change from baseline
Standard Deviation 91.240833
57.36857 % change from baseline
Standard Deviation 226.50576
Change in Percentage of Total Cells in Blood
Monocytes
0.05858 % change from baseline
Standard Deviation 24.446709
30.65211 % change from baseline
Standard Deviation 65.329419
1.67563 % change from baseline
Standard Deviation 46.936967
Change in Percentage of Total Cells in Blood
Lymphocytes
10.21926 % change from baseline
Standard Deviation 35.449159
-1.58746 % change from baseline
Standard Deviation 23.455210
14.24407 % change from baseline
Standard Deviation 26.363322
Change in Percentage of Total Cells in Blood
Neutrophils
1.62215 % change from baseline
Standard Deviation 24.058407
0.13700 % change from baseline
Standard Deviation 10.8890617
-3.29570 % change from baseline
Standard Deviation 10.559662

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 55

Population: All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement.

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change in Concentrations of Inflammatory Marker in Plasma/Blood
ELA2
-7.13 % change from baseline
Standard Deviation 30.726
-17.01 % change from baseline
Standard Deviation 33.050
-26.33 % change from baseline
Standard Deviation 30.972
Change in Concentrations of Inflammatory Marker in Plasma/Blood
IL-13
5.158 % change from baseline
Standard Deviation 45.4151
10.197 % change from baseline
Standard Deviation 53.7029
-1.622 % change from baseline
Standard Deviation 5.5691
Change in Concentrations of Inflammatory Marker in Plasma/Blood
IL-1ß
44.9813 % change from baseline
Standard Deviation 149.88595
32.7901 % change from baseline
Standard Deviation 121.71539
4.7453 % change from baseline
Standard Deviation 72.39394
Change in Concentrations of Inflammatory Marker in Plasma/Blood
IL-4
68.849 % change from baseline
Standard Deviation 280.7619
22.678 % change from baseline
Standard Deviation 98.3923
-19.865 % change from baseline
Standard Deviation 35.6127
Change in Concentrations of Inflammatory Marker in Plasma/Blood
IL-5
73.36 % change from baseline
Standard Deviation 214.724
20.57 % change from baseline
Standard Deviation 257.416
-5.30 % change from baseline
Standard Deviation 99.117
Change in Concentrations of Inflammatory Marker in Plasma/Blood
IL-6
-26.0682 % change from baseline
Standard Deviation 36.92257
-35.8383 % change from baseline
Standard Deviation 82.30541
-48.4230 % change from baseline
Standard Deviation 51.59468
Change in Concentrations of Inflammatory Marker in Plasma/Blood
IL-8
26.916 % change from baseline
Standard Deviation 47.0832
6.986 % change from baseline
Standard Deviation 54.7421
57.464 % change from baseline
Standard Deviation 176.8141
Change in Concentrations of Inflammatory Marker in Plasma/Blood
MCP1
20.019 % change from baseline
Standard Deviation 86.8398
-13.923 % change from baseline
Standard Deviation 31.9128
51.441 % change from baseline
Standard Deviation 173.5531
Change in Concentrations of Inflammatory Marker in Plasma/Blood
MMP9
-10.922 % change from baseline
Standard Deviation 52.3542
-9.087 % change from baseline
Standard Deviation 39.4842
-27.524 % change from baseline
Standard Deviation 34.8440
Change in Concentrations of Inflammatory Marker in Plasma/Blood
MPO
-6.051 % change from baseline
Standard Deviation 21.3202
-9.661 % change from baseline
Standard Deviation 26.7605
-14.232 % change from baseline
Standard Deviation 26.6217
Change in Concentrations of Inflammatory Marker in Plasma/Blood
TNF-α
-10.499 % change from baseline
Standard Deviation 24.7753
-16.184 % change from baseline
Standard Deviation 25.6551
-1.585 % change from baseline
Standard Deviation 27.5520
Change in Concentrations of Inflammatory Marker in Plasma/Blood
CRP
-12.087 % change from baseline
Standard Deviation 102.3304
29.028 % change from baseline
Standard Deviation 345.0216
-61.732 % change from baseline
Standard Deviation 40.0405
Change in Concentrations of Inflammatory Marker in Plasma/Blood
Fibrinogen
0.5 % change from baseline
Standard Deviation 15.39
-0.4 % change from baseline
Standard Deviation 13.88
-7.7 % change from baseline
Standard Deviation 22.38

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 56

Population: 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

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=20 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Number of Participants With COPD Exacerbation
3 Participants
2 Participants
5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Screen) to Day 55

Population: 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

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.

Outcome measures

Outcome measures
Measure
Treatment A
n=19 Participants
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment B
n=21 Participants
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM
Treatment C
n=20 Participants
Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM
Change From Baseline in Forced Vital Capacity (FVC)
-0.087 L
Standard Deviation 0.3475
0.007 L
Standard Deviation 0.2290
-0.105 L
Standard Deviation 0.3117

Adverse Events

Treatment A

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Treatment B

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Treatment C

Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Treatment A
n=20 participants at risk
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55
Treatment B
n=21 participants at risk
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55
Treatment C
n=20 participants at risk
Multiple oral doses of placebo BID on Days 1 - 55
Respiratory, thoracic and mediastinal disorders
Acute Exacerbation of COPD
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • 56 days

Other adverse events

Other adverse events
Measure
Treatment A
n=20 participants at risk
Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55
Treatment B
n=21 participants at risk
Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55
Treatment C
n=20 participants at risk
Multiple oral doses of placebo BID on Days 1 - 55
Eye disorders
Dry eye
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Eye disorders
Eye irritation
0.00%
0/20 • 56 days
4.8%
1/21 • Number of events 1 • 56 days
0.00%
0/20 • 56 days
Gastrointestinal disorders
Diarrhoea
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Gastrointestinal disorders
Dry mouth
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • Number of events 1 • 56 days
Gastrointestinal disorders
Dyspepsia
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Gastrointestinal disorders
Large intestine polyp
0.00%
0/20 • 56 days
4.8%
1/21 • Number of events 1 • 56 days
0.00%
0/20 • 56 days
Gastrointestinal disorders
Nausea
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Infections and infestations
Bronchitis
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • Number of events 1 • 56 days
Infections and infestations
Bronchopneumonia
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Infections and infestations
Epididymitis
0.00%
0/20 • 56 days
4.8%
1/21 • Number of events 1 • 56 days
0.00%
0/20 • 56 days
Infections and infestations
Folliculitis
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Infections and infestations
Gastroenteritis viral
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Infections and infestations
Herpes zoster
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Infections and infestations
Nasopharyngitis
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • 56 days
Infections and infestations
Subcutaneous abscess
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • 56 days
Infections and infestations
Upper respiratory tract infection
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
10.0%
2/20 • Number of events 2 • 56 days
Infections and infestations
Urinary tract infection
5.0%
1/20 • Number of events 1 • 56 days
9.5%
2/21 • Number of events 2 • 56 days
0.00%
0/20 • 56 days
Injury, poisoning and procedural complications
Chest injury
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • Number of events 1 • 56 days
Injury, poisoning and procedural complications
Skeletal injury
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • Number of events 1 • 56 days
Metabolism and nutrition disorders
Diabetes mellitus
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/20 • 56 days
4.8%
1/21 • Number of events 1 • 56 days
0.00%
0/20 • 56 days
Musculoskeletal and connective tissue disorders
Neck pain
5.0%
1/20 • Number of events 1 • 56 days
4.8%
1/21 • Number of events 1 • 56 days
0.00%
0/20 • 56 days
Nervous system disorders
Dizziness
0.00%
0/20 • 56 days
4.8%
1/21 • Number of events 1 • 56 days
0.00%
0/20 • 56 days
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
15.0%
3/20 • Number of events 3 • 56 days
9.5%
2/21 • Number of events 2 • 56 days
25.0%
5/20 • Number of events 5 • 56 days
Respiratory, thoracic and mediastinal disorders
Cough
0.00%
0/20 • 56 days
9.5%
2/21 • Number of events 2 • 56 days
25.0%
5/20 • Number of events 5 • 56 days
Respiratory, thoracic and mediastinal disorders
Dyspnoea
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • Number of events 1 • 56 days
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • Number of events 1 • 56 days
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • Number of events 1 • 56 days
Skin and subcutaneous tissue disorders
Drug eruption
0.00%
0/20 • 56 days
0.00%
0/21 • 56 days
5.0%
1/20 • Number of events 1 • 56 days
Skin and subcutaneous tissue disorders
Rash
0.00%
0/20 • 56 days
4.8%
1/21 • Number of events 1 • 56 days
0.00%
0/20 • 56 days
Surgical and medical procedures
Large intestinal polypectomy
0.00%
0/20 • 56 days
4.8%
1/21 • Number of events 1 • 56 days
0.00%
0/20 • 56 days
Surgical and medical procedures
Tooth extraction
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days
Vascular disorders
Hypertension
5.0%
1/20 • Number of events 1 • 56 days
0.00%
0/21 • 56 days
0.00%
0/20 • 56 days

Additional Information

Director of Clinical Trials

Yungjin Pharm. Co., Ltd.

Phone: 82-2-2041-8318

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place