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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
61
twice daily \[BID\]
twice daily \[BID\]
twice daily \[BID\]
UAB Lung Health Center
Birmingham, Alabama, United States
Florida Pulmonary Research Institute, LLC
Winter Park, Florida, United States
Aventiv Research Inc.
Columbus, Ohio, United States
Temple Lung Center, Temple University Hospital
Philadelphia, Pennsylvania, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to Day 56
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.
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Time frame: 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 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)
Time frame: 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.
Time frame: 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.
Time frame: Baseline to Day 55