Chronic Obstructive Pulmonary Disease MedDRA version: 18.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Interventions
Product Name: Danirixin
Product Code: GSK1325756
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Danirixin
CAS Number: 954126-98-8
Current Sponsor code: GSK1325756
Other descriptive name:
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Male or female aged between 40 and 75 years of age inclusive, at the time of signing the informed consent 2. 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 mg/mL 3. 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 4. Subjects with a post-bronchodilator FEV1/FVC ratio of 40 MlU/ml and estradiol 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 8. 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 9. AST and ALT 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. 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 2. Pulse Oximetry levels 21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~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. 12. Current or expected use of proton pump inhibitors or histamine H2-receptor antagonists during the study period 13. 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). 14. Subjects with peripheral blood neutrophil count (PBN) <2x109/L 15. Subject with history of previous lung surgery (e.g. lobectomy, pneumonectomy, or lung volume reduction) 16. Requiring the use of oral or injectable CYP3A4 or BCRP substrates with a narrow therapeutic index (refer to Section 5.11.2.) 17. Current or expected chronic use of macrolides during the study period for the prevention of COPD exacerbations. Examples of "chronic use" would be daily or two-three times per week for at least 3 mont
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary-Part A & Part B To evaluate the safety and tolerability of danirixin compared with placebo in symptomatic COPD subjects with mild to moderate airflow limitation Primary -Part A To characterize the pharmacokinetics of danirixin in symptomatic COPD subjects with mild to moderate airflow limitation Primary-Part B To characterize the effect of danirixin compared with placebo on the incidence and severity of respiratory symptoms and COPD exacerbations in symptomatic COPD subjects with mild to moderate airflow limitation ;Secondary Objective: Secondary- Part B To characterize the pharmacokinetics of danirixin in symptomatic COPD subjects with mild to moderate airflow limitation To further characterize clinical efficacy of danirixin in symptomatic COPD subjects with mild to moderate airflow limitation ;Primary end point(s): Primary-Part A & Part B •Adverse Events (AEs) •Vital Signs •ECG •Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis) •Lung Function (spirometry) Primary -Part A Standard pharmacokinetic parameters for danirixin (i.e. AUC, Cmax, Tmax) Primary-Part B •Health Care Resource Utilization (HCRU) defined COPD exacerbations (new prescription antibiotics or oral corticosteroids, hospitalization or emergency room visits for management of COPD exacerbation) •Monthly weighted means of EXACT Respiratory Symptoms (EXACT-RS);Timepoint(s) of evaluation of this end point: Week 0, 2, 4, 8, 12, 16, 20, 24, 32, 40, 52, 56 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part B •Standard pharmacokinetic parameters for danirixin (i.e.AUC, Cmax, Tmax) •EXACT-PRO event •EXACT-PRO total score weighted means •Time to first HCRU COPD exacerbation •Time to first moderate HCRU COPD exacerbation •Time to first severe HCRU COPD exacerbation •Time to first EXACT-PRO event •EXACT-PRO events severity and duration •Monthly weighted mean EXACT-RS domain scores (breathlessness, cough & sputum, chest symptoms) •COPD Assessment Test (CAT) •Lung function (spirometry) •Physician Global Assessment •Patient Global Rating of Severity Patient Global Impression of Change ;Timepoint(s) of evaluation of this end point: Week 0, 2, 4, 8, 12, 16, 20, 24, 32, 40, 52, 56 | — |
Countries
Germany, United States
Contacts
Public ContactClincial Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed