A 5-way Treatment Period Trial of Single Doses of Intranasal GSK256066 in Patients With Rhinitis

A Randomised, Open, Placebo-controlled 5-way Crossover Trial of Single Doses of Intranasal GSK256066 in Subjects With Seasonal Allergic Rhinitis (SAR).

This current study is planned as a dedicated pharmacodynamic (effect of drug on the body) study to investigate the dose response in rhinitic subjects at doses where GSK256066 has been proven to work (200mcg) or expected to (50mcg) work. This study also aims to investigate the lower end of the predicted therapeutic range.

Inclusion Criteria:

• The subject is healthy.
• Body mass index less than 29.0 kg/m² , weight range of 55.0kg (females 50kg) to 95.0kg inclusive.
• They have a history of hayfever (repeated yearly episodes).
• They have a positive skin prick test for grass pollen at or within the 12 months preceding the screening visit.
• They have a positive radioallergosorbent test for grass pollen at or within the 12 months preceding the screening visit.
• non-smokers.
• They must have a baseline FEV1>80% predicted and a baseline FEV1(maximum recorded value)/ forced vital capacity (FVC) (maximum recorded value)>70%
• They are capable of giving informed consent
• They are available to complete all study measurements.

Exclusion Criteria:

• Pregnant or nursing females.
• Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception.
• The subject has structural nasal abnormalities or nasal polyposis.
• Any respiratory disease other than mild stable asthma that is controlled with occasional use of as-needed short-acting beta-agonists and associated with normal lung function.
• The subject has a history of drug or other allergy that may contraindicate participation.
• The subject has participated in a study with a new molecular entity during the previous 4 months or in any clinical study in the previous 3 months
• The subject is concurrently participating in another clinical study and is exposed to an investigational or a non-investigational drug or device.
• The subject has a screening QTc value >450msec, PR interval outside the range 120 to 240msec or an ECG that is not suitable for QT measurements.In addition subjects will be excluded if they have a history of atrial and ventricular arrhythmia.
• The subject has a supine blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
• The subject has donated a unit of blood (450mL) within the previous 3 months or intends to donate within 3 months of completing the study.
• The subject is currently taking regular (or a course of) medication whether prescribed or not, including steroids, vitamins, and herbal remedies (e.g. St. John's Wort). Paracetamol (<2g/day) and occasional as needed use of short-acting beta agonists is permitted.
• Past or present disease which may affect study. outcome
• The subject regularly, or on average, drinks more than 4 units of alcohol per day - where 1 unit = ½ pint of beer (284mL), or 1 glass of wine (125mL), or 1 measure of spirit (25mL).
• The subject is at risk of non-compliance with the study procedures/restrictions.
• The subject has Hepatitis B, Hepatitis C, or HIV virus.