Danirixin

This 2-part study will be carried out on healthy elderly subjects to evaluate relative bioavailability of danirixin formulations. Part A will support the selection of the formulation and Part B will assess food effect, bioavailability and pharmacokinetic (PK) profile of selected formulation from Part A. Danirixin is currently administered with food, therefore the investigation of food effect for the selected formulation could potentially enable dosing without food. Approximately 16 subjects will be included in Part A and approximately 24 subjects will be included in Part B. Both parts will include a screening phase, treatment phase with in-between washout period and a follow-up phase.

The inflammation associated with COPD is characterized by a prominent infiltration of neutrophils in lung tissue and airways. The CXC chemokine receptor type 2 (CXCR2) plays a pivotal role in neutrophil recruitment to the lungs resulting in progressive fibrosis, airway stenosis, and destruction of the lung parenchyma characteristic of COPD. There is a paucity of novel therapies that target these symptoms, and there are no currently available therapies that modify disease progression in COPD. Danirixin (GSK1325756) is a selective CXCR2 antagonist being developed as a potential anti-inflammatory agent for the treatment of COPD and influenza. This study is a mechanistic study which aims to evaluate the effect of danirixin in reducing neutrophil extracellular traps (NETs) formation (or NETosis). Subjects will be randomized (3:1) to receive danirixin hydrobromide (HBr) 35 milligram (mg) orally twice daily or matching placebo for 14 days. Subjects may continue to use rescue medication(s) and inhaled COPD maintenance medication(s) during the study. The study will consist of a screening period of up to 30 days, a 2 week treatment period, and a 1-week follow-up visit via phone call. Approximately 50 subjects will be screened to obtain approximately 24 subjects to complete the study.