Study will investigate the pharmacodynamics of a dual pharmacophore in which a combination
of GSK961081 and Propanolol is used to give a total effect of bronchodilation.
Minimum age: 18 Years.
Maximum age: 50 Years.
- Healthy adult males aged between 18 and 50 years.
- Body mass index within the range 19-29. 9 kg/m2.
- FEV1 ≥ 80% predicted and a FEV1/ Forced Vital Capacity (FVC) ratio ≥ 0. 7
- Signed and dated written informed consent is obtained from the subject
- The subject is able to understand and comply with the protocol requirements,
instructions and protocol-stated restrictions.
- The subject has an increase in sGAW of ≥15% over pre-dose baseline within 2 h of
administration of 400 µg salbutamol by MDI inhaler at screening or in the 3 months
- The subject has an increase in sGAW of ≥25% over pre-dose baseline within 2 h
following 80 µg ipratropium bromide at screening or in the 3 months before screening.
- Subjects who are current non-smokers who have not used any tobacco products in the
6-month period preceding the screening visit and have a pack history of ≥ 10 pack
- Any clinically relevant abnormality identified at the screening medical assessment
(physical examination/medical history), clinical laboratory tests, or ECG (12-lead or
- A history of respiratory disease (i. e. history of asthmatic symptoms).
- Clinically significant abnormal 12 lead ECG at
- A subject in whom ipratropium bromide, salbutamol or propranolol are contraindicated.
- 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 45-90 beats per minute (bpm) at screening.
- The subject has donated a unit of blood within the 56 days or intends to donate
within 56 days after completing the study.
- The subject is currently taking regular (or course of) medication whether prescribed
or not (with the exception of contraceptives, 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 medical monitor the medication will not interfere with the study
procedures or compromise subject safety.
- The subject has participated in a clinical study with a New Chemical Entity (NCE)
within the past 3 months.
- Exposure to more than four new chemical entities within 12 months prior to the first
- 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 history of regular alcohol consumption exceeding weekly intake of alcohol greater
than 28 units for males, or an average daily intake of greater than 4 units.
- Are unable to use the inhaler correctly.
- The subject has a history of drug or other allergy, which, in the opinion of the
Investigator, contraindicates their participation.
- The subject has had a lower respiratory tract infection within 4 weeks of study
- Subject is unable to perform the sGAW measurements