Study of GSK961081 in Healthy Volunteer Subjects

Exclusion Criteria

• •Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead or Holter).
• •A history of breathing problems (i.e. history of asthmatic symptoms). Screening lung function tests (FEV1, FVC and sGaw) will be performed to confirm normal lung function parameters.
• •A mean QTc(B) and QTc(F) value at screening \>430msec, the 3 screening ECGs are not within 10% of the mean, a PR interval outside the range 120-210msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave).
• •A supine blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
• •A supine mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
• •The subject has donated a unit of blood within the 90 days or intends to donate within 90 days after completing the study.
• •A history of claustrophobia such that they may not tolerate plethysmography measurements.
• •The subject is currently taking regular (or course of) medication whether prescribed or not, including vitamins and herbal remedies such as St John's Wort.
• •The subject has used prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (which ever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety.
• •The subject has participated in a clinical study with another New Chemical Entity (NCE) within the past 112 days or a clinical study with any other drug during the previous 84 days.
• •The subject is infected with the Hepatitis B, Hepatitis C, or HIV virus.
• •The subject has a positive pre-study urine cotinine/ breath carbon monoxide test, urine drug/urine alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbituates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
• •A history of regular alcohol consumption exceeding weekly intake of alcohol greater than 28 units, or an average daily intake of greater than 4 units.
• •Are unable to use the Prodose AAD nebuliser device correctly.
• •An unwillingness of subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or tubal ligation if the woman could become pregnant from the time of the first dose study medication until 90 days post-dose.
• •The subject has a history of drug or other allergy, which, in the opinion of the responsible physician, contraindicates their participation.
• •The subject has a history of hypersensitivity to Salbutamol or Ipratropium bromide, and for those subjects in cohorts III and IV, hypersensitivity to a beta-blocker.
• •The subject has had a lower respiratory tract infection within 4 weeks of study start