Clinical trial NCT02272634: A Phase 2a Study to Assess Safety, Daily Symptoms, PK, and Biomarkers of YPL-001 in COPD Patients
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Lead sponsor: Yungjin Pharm. Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2014-10-23
Enrollment: 61
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events
timeFrame: Up to Day 56
measure: Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
timeFrame: Up to Day 56
measure: Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
timeFrame: Up to Day 56
measure: Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
timeFrame: Up to Day 56
Secondary outcomes:
measure: Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily
timeFrame: Baseline to Day 55
measure: Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
timeFrame: Baseline to Day 55
measure: Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale)
timeFrame: Baseline to Day 55
measure: Change From Baseline of Calculated Score From Duke Activity Status Index (DASI)
timeFrame: Baseline to Day 55
Other outcomes:
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline (Screen) to Day 55
measure: Change From Baseline in Inspiratory Capacity (IC)
timeFrame: Baseline (Screening) to Day 55
measure: Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio
timeFrame: Baseline to Day 55
measure: Transition Dyspnea Index (TDI) Focal Score
timeFrame: Baseline to Day 55
measure: Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT)
timeFrame: Baseline to Day 55
measure: Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL)
timeFrame: Baseline (Day -1) and Day 55
measure: Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
timeFrame: Baseline (Day -1) and Day 55
measure: Change in Percentage of Total Cells in Blood
timeFrame: Baseline to Day 55
measure: Change in Concentrations of Inflammatory Marker in Plasma/Blood
timeFrame: Baseline to Day 55
measure: Number of Participants With COPD Exacerbation
timeFrame: Baseline to Day 56
measure: Change From Baseline in Forced Vital Capacity (FVC)
timeFrame: Baseline (Screen) to Day 55
Locations:
city: Birmingham
country: United States
facility: UAB Lung Health Center
state: Alabama
city: Winter Park
country: United States
facility: Florida Pulmonary Research Institute, LLC
state: Florida
city: Columbus
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Philadelphia
country: United States
facility: Temple Lung Center, Temple University Hospital
state: Pennsylvania
Study officials:
affiliation: Temple University
name: Gerard J Criner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Kirklin Clinic of UAB Hospital
name: Mark T Dransfield, MD
role: PRINCIPAL_INVESTIGATOR
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