Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Interventions
Product Name: SB681323 Tablets
Product Code: SB681323
Pharmaceutical Form: Tablet
Current Sponsor code: SB681323
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5
Sponsors
GlaxoSmithKline R&D
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male adults or female adults of non-childbearing potential who are between 40 and 75 years of age (inclusive). Note: A female is eligible to enter and participate in the study if she is of nonchildbearing potential (i.e. physiologically incapable of becoming pregnant), including any female who is post-menopausal. For the purposes of this study, post menopausal is defined as one year without menses. 2. Subjects with a clinical diagnosis of COPD in accordance with the European Respiratory Society Consensus Statement and subjects categorised with moderate COPD as defined by the GOLD guidelines of 2003 [GOLD, 2003]. 3. Subjects with a cigarette smoking history of = 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or the equivalent). Both current and former smokers are eligible to be enrolled. A former smoker is defined as a subject who has not smoked for =6 months at Visit 1. 4. Subjects with a post-bronchodilator FEV1 to FVC ratio (FEV1:FVC) 3mg/L at Visit 1a. 2. Subjects with no evidence of an ongoing acute infection or sinus symptoms. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Women who are pre-menopausal and of child-bearing potential. 2. Subjects with a current diagnosis of asthma. 3. Subjects who have required hospitalisation or treatment with oral corticosteroids and/or antibiotic therapy for acute worsening of COPD or lower respiratory tract infection in the 6 weeks prior to Screening. 4. Subjects with active tuberculosis, sarcoidosis or clinically overt bronchiectasis. 5. Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with chronic inflammation (e.g. Inflammatory Bowel Disease). 6. Subjects with chronic infections such as gingivitis, periodontitis, prostatitis, gastritis, and urinary tract infections. 7. Subjects with clinically significant renal disease, diabetes mellitus/metabolic syndrome, hypertension or any other clinically significant cardiovascular, neurological, endocrine, or haematological abnormalities that are uncontrolled on permitted therapy. 8. Subjects with clinically significant gastrointestinal or hepatic abnormalities. 9. Subjects with hypoxaemia. (All subjects must have an O2 saturation of =88% on room air.) 10. History of Gilbert's syndrome or elevated bilirubin concentrations. Subjects with a total bilirubin concentration above the upper limit of normal at Screening will be excluded 11. History of increased liver function tests (ALT, AST) above upper limit of normal in the past 6 months and/or liver function tests (bilirubin, ALT, AST) above upper limit of normal at Screening (Visit 1). 12. Subjects who have undergone recent surgery including lung volume reduction surgery or have conditions that prevent them from performing spirometry. 13. Subjects who require treatment with any of the following from the Screening (Visit 1) until study completion: Inhaled corticosteroids Inhaled cromolyn sodium or nedocromil Xanthines (theophylline preparations). Leukotriene modifiers Tiotropium Long-acting inhaled beta2-agonists (salmeterol, formoterol) Oral beta2-agonists 14. Subjects who have received treatment with oral, intravenous or intra-articular corticosteroids within 6 weeks of Screening or thereafter 15. Subjects with any known hypersensitivity to salbutamol or ipratropium bromide. A subject will not be eligible for randomisation at the end of the run-in period if the following additional criterion applies: 1. Subjects who have experienced an exacerbation during the run-in period requiring treatment with oral corticosteroids and/or antibiotics and/or hospitalisation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the safety and tolerability of SB-681323 administered orally for 28 days in subjects with COPD. • To assess the systemic anti-inflammatory activity of SB-681323 administered orally for 28 days in subjects with COPD as determined by serum concentrations of CRP.;Secondary Objective: • To assess the pulmonary anti-inflammatory activity of SB-681323 administered orally for 28 days in subjects with COPD. • To assess the systemic anti-inflammatory activity of SB-681323 administered orally for 28 days in subjects with COPD as determined by other markers. • To assess the effect on pulmonary function of SB-681323 administered orally for 28 days in subjects with COPD. • To assess the effect on dyspnoea of SB-681323 administered orally for 28 days in subjects with COPD. • To assess the pharmacokinetics of SB-681323 in subjects with COPD. • To explore the potential correlation between plasma concentrations of SB-681323 and serum concentrations of CRP.;Primary end point(s): There are two primary endpoints for this study. These are: • The safety and tolerability of SB-681323 administered orally for 28 days as assessed by the incidence of alanine aminotransferase (ALT) concentrations >3 x ULN • The mean ratio to baseline after 28 days treatment of the serum concentration of CRP. | — |
Countries
Denmark, Finland, Germany, United Kingdom
Outcome results
None listed