E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the safety and tolerability of SB-681323 administered orally for 28 days in subjects with COPD.
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E.2.2 | Secondary objectives of the trial |
• 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. • 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. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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) < 0.7 at Visit 1. Subjects will be assessed 30 (± 5) minutes after receiving salbutamol 400 µg. 5. Subjects with a post-bronchodilator FEV1 ≥ 50% and < 80% of predicted normal for height, age and sex at Visit 1. Subjects will be assessed 30 (± 5) minutes after receiving salbutamol 400 µg. prior to Screening. 6. Subjects capable of providing signed written informed consent to participate.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The Primary endpoint for this study is: • 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
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |