Investigation of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy of Oral Danirixin in Symptomatic COPD Subjects With Mild to Moderate Airflow Limitation at Risk for Exacerbations
Saves the questions and what to expect into your notes, next to the visit they belong to.
Keep this study
Lead
GlaxoSmithKline
Age
40–70
Sex
ALL
Healthy volunteers
Not accepted
You may be eligible if
Male or female aged between 40 and 70 years of age inclusive, at the time of signing the informed consent
Subjects with a documented history of COPD exacerbation(s) in the 12 months prior to study participation meeting at least one of the following criteria: \>=2 COPD exacerbations resulting in prescription for antibiotics and/or oral corticosteroids or hospitalization or extended observation in a hospital emergency room or outpatient center; 1 COPD exacerbation resulting in prescription for antibiotics and/or oral corticosteroids or hospitalization or extended observation in a hospital emergency room or outpatient center and a plasma fibrinogen concentration at screening \>=3.5 milligram/milliliter (mg/mL)
Diagnosis of symptomatic chronic obstructive pulmonary disease with mild to moderate airflow obstruction (COPD-GOLD I or II) for at least 2 years based on American Thoracic Society (ATS)/ European Respiratory Society (ERS) current guidelines or symptoms consistent with COPD for at least 2 years
Subjects with a post-bronchodilator FEV1/FVC ratio of \< 0.7 and FEV1 \>=50% of predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equation at Visit 1
A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy \[for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\]; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milli international units/mL (MIU/mL) and estradiol \< 40 picogram (pg)/mL (\<147 picomole/Liter \[pmol/L\]) is confirmatory\]. Females on hormone replacement therapy (HRT) will not be enrolled in the study.
Body weight \>=45 kilogram (kg)
Current smokers and former smokers with a cigarette smoking history of \>=10 pack years (1 pack year =20 cigarettes smoked per day for 1 year or equivalent). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1
Subjects with a history of respiratory symptoms, including chronic cough and/or mucus hypersecretion on most days for at least the previous 3 months prior to Visit 1
Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<2x upper limit of normal (ULN); alkaline phosphatase and bilirubin \<=1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
Able to perform lung function tests reliably
Based on single or averaged corrected QT (QTc) values of triplicate ECGs obtained over a brief recording period: Fridericia-corrected QTc (QTcF) \< 450 milliseconds (msec); or QTc \< 480 msec in subjects with Bundle Branch Block
Subjects must have the ability to use an electronic diary on a daily basis \[Part B only\]
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
You may not be if
Diagnosis of asthma, or other clinically relevant lung disease (other than COPD), e.g. sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis or lung cancer; Subject with alpha-1-antitrypsin deficiency as the underlying cause of COPD
Pulse Oximetry levels \<88% (at rest on room air) at screening
Less than 14 days have elapsed from completion of a course of antibiotics or oral corticosteroids for a recent COPD exacerbation.
Diagnosis of Pneumonia (chest X-Ray or computed tomography \[CT\] confirmed) within the last 3 months prior to screening
History or current evidence of clinically significant renal disease, diabetes mellitus/metabolic syndrome, hypertension or any other clinically significant cardiovascular, neurological, endocrine, or hematological abnormalities that are uncontrolled on permitted therapy. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subjects at risk through study participation, or which would affect the safety analysis or other analysis if the disease/condition exacerbated during the study.
A positive pre-study drug/alcohol screen
A positive test for human immunodeficiency virus (HIV) antibody
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
History of regular alcohol consumption within 6 months of the study defined as: For non United States of America (US) sites: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits; For US sites: an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
Current or expected use of proton pump inhibitors or histamine H2-receptor antagonists during the study period
Chest X-ray (posteroanterior with lateral) or CT scan reveals evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD (historic data up to 1 yr may be used).
Subjects with peripheral blood neutrophil count (PBN) \<2x10\^9/Liter
Subject with history of previous lung surgery (e.g. lobectomy, pneumonectomy, or lung volume reduction)
Requiring the use of oral or injectable Cytochrome P450 3A4 (CYP3A4) or breast cancer resistance protein (BCRP) substrates with a narrow therapeutic index
Clareo Health | Investigation of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy of Oral Danirixin in Symptomatic COPD Subjects With Mild to Moderate Airflow Limitation at Risk for Exacerbations
