A Study to Investigate the Effect of SB-705498 on Chronic Cough

Two Part Study to Investigate Pharmacokinetics (PK) & Pharamcodynamics (PD) of SB-705498 in Cough. Part A:Open Label Study in Healthy Subjects to Determine Exposure to SB-705498. Part B:Double-blind, Placebo Controlled, Cross Over Study to Investigate Effect of SB-705498 on Capsaicin Induced Cough and 24 Hour Cough Counts in Cough Patients

This study is designed to loook at the affect of oral SB-705498 on cough following an inhaled capsaicin challenge

Inclusion Criteria:

• Male or female between 30 -75 (Part A) and 18-75 (Part B) years of age inclusive.
• Non-child bearing women or women of child bearing potential if they agree to use contraception as indicated by the protocol
• Non-smoker for at least 6 months with a pack history <5 pack years (Pack years = (No. of cigarettes smoked/day/20) x No. of years smoked).
• Body weight > 50 kg and body mass index (BMI) within the range 19 - 30.0 kg/m2 (inclusive).
• Capable of giving written informed consent.
• Agree to use contraception listed as acceptable
• Normal 12-lead ECG at screening.
• Chronic cough (Part B only)
• Good general health, apart from chronic cough (part B only), as determined by a responsible physician.

Exclusion Criteria:

• A history of gastrointestinal, hepatic, renal or multiple cardiovascular risk factors.
• Positive pre-study drug/alcohol screen.
• Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive test for human immunodeficiency virus (HIV) antibody (if determined by the local standard operating procedures (SOPs)).
• History of regular alcohol consumption within 6 months of the study.
• Exposure to more than four new chemical entities within 12 months prior to the start of the study.
• Participation in a clinical trial with a new molecule entity or any other clinical trial within 30 days of the start of the study.
• Use of prescription or non-prescription drugs, as well as of vitamins, herbal and dietary supplements (including St John's Wort) within 7 days prior to study.
• known history of lung cancer
• current treatment with oral corticosteriods or other immunosupressive agents
• FEV1 less than 80% of predicted value at screening
• Any subject who does not reach C5 following 250uM oral capsaicin
• History of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation.
• Donation of blood or blood products in excess of 500mL within a 56 day period prior the start study.
• Pregnant females as determined by positive serum or urine human chorionic gonadotropin (hCG) test at screening or prior to dosing.
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to dosing.