A 12-week, randomised, double-blind, placebo-controlled study to assess the anti-inflammatory activity, efficacy and safety of GW856553 in subjects with chronic obstructive pulmonary disease (COPD)

INTERVENTION: Product Name: GW856553 2.5mg Tablets Product Code: GW856553 Pharmaceutical Form: Tablet Current Sponsor code: GW856553 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2.5‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Viani forte 50µg/500µg Diskus Product Name: Viani forte 50µg/500µg Diskus Pharmaceutical Form: Inhalation powder, pre‐dispensed INN or Proposed INN: Salmeterol (as salmeterol xinafoate) Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 50µg salmeterol‐ INN or Proposed INN: Fluticasone propionate Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 500 µg‐ Pharmaceutical form of the placebo: Inhalation powder, pre‐dispensed Route of administration of the placebo: Inhalation use Product Name: GW856553 5mg Tablets Product Code: GW856553 Pharmaceutical Form: Tablet Current Sponsor code: GW856553 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Chronic obstructive pulmonary disease ; MedDRA version: 9.1 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease PRIMARY OUTCOME: Main Objective: To evaluate the effects of 12 weeks of treatment with GW856553 7.5 mg BID compared with placebo on the percentage of sputum neutrophils at 12 weeks. Primary end point(s): Percentage of neutrophils in induced sputum at week 12. Secondary Objective: To evaluate the effects of 12 weeks of treatment with GW856553 7.5 mg BID compared with placebo on:; ‐ Pulmonary function assessed by body plethysmography; ‐ Pulmonary function assessed by spirometry; ‐ Pulmonary function assessed by impulse oscillometry; ‐ Parameters measured in induced sputum ; ‐ Serum fibrinogen and additional systemic inflammation biomarkers ; ‐ Levels of ex vivo lipopolysaccharide (LPS) induced tumour necrosis factor (TNF)‐alpha in whole blood pre‐dose and 2 h post‐dose at selected centres. ; ‐ Levels of ex vivo sorbitol induced phosphorylation of heat shock protein 27 (pHSP27) in whole blood pre‐dose and 2 h post‐dose at selected centres.; ; Refer to the protocol for full details.; 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 non‐childbearing potential (i.e. physiologically incapable of becoming pregnant). This includes any female who is post‐menopausal. For the purposes of this study, post menopausal is defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. Postmenopausal status may be confirmed by serum FSH and oestradiol concentrations at screening if deemed necessary by the PI. Surgical sterility will be defined as females who have had a hysterectomy and/or bilateral oophorectomy or tubal ligation. 2. Chronic obstructive pulmonary disease diagnosis: an established clinical history of COPD in accordance with the following description by the American Thoracic Society / European Respiratory Society