A study to investigate the effects of GW876008 on brain activation during emotional processing in healthy subjects.

Healthy males or females aged 18-50 years, inclusive.

• STAI-trait score = or > 40.
• STAI-state score <50th percentile of the normal population distribution.
• Female subjects of non-childbearing.
• Female subjects of childbearing potential must agree to use appropriate contraception.
• Healthy subjects, as determined by a responsible physician
• Body weight ≥ 50 kg (110 lbs), and BMI within the range 19-29.9 kg/m2 inclusive.
• Demonstrates no significant evidence of active disease, physical or mental impairment when assessed by qualified personnel
• Non-smoker (abstinence from smoking for at least 6 months before the start of the study).
• Normal electrocardiogram.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Read, comprehend, and write English at a sufficient level to complete study-related materials.
• Provide a signed and dated written informed consent prior to study participation

As a result of any of the medical interview, physical examination, evaluation of mental state and psychiatric history or screening investigations the physician responsible considers the subject unfit for the study.

• Any history of suicidal attempts or behaviour.
• Any history or current diagnosis of a psychiatric illness.
• Any history of an endocrine disorder including, but not limited to, diabetes or disorders of the hypothalamus, pituitary, adrenal, or thyroid glands, or gonadal disorder or dysfunction of the reproductive organs.
• Abnormal pepsinogen I level at screening.
• Liver Function Tests (LFTs) elevated above the reference range at pre-study screening that remain elevated with a repeat LFT
• Any other clinically significant laboratory abnormality.
• Positive faecal occult blood test.
• Positive pre-study urine drug/alcohol breath screen.
• Positive pre-study HIV 1/2, Hepatitis B surface antigen and positive Hepatitis C antibody result within 3 months of the start of the study.
• Pre-existing or current Helicobactor pylori infection.
• History of alcohol/drug abuse or dependence within 12 months of the study
• Consumption of grapefruit juice or grapefruit within 14 days prior to the first dose of study medication.
• History of peptic ulcer disease.
• Abnormal screening ECG
• History of long QT syndrome (personal or family) or other cardiac conduction disorder, or other clinically significant cardiac disease.
• Systolic blood pressure < 90mmHg or >140mmHg; diastolic blood pressure < 60mmHg or > 90mmHg; pulse rate < 40bpm or > 90bpm.
• Participation in a clinical trial with a drug or new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Use of 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 (whichever is longer) prior to the first dose of study medication.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
• History or current diagnosis of acute narrow angle glaucoma.
• Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period.
• Current or recent (within one year) gastrointestinal disease; a history of malabsorption, esophageal reflux, irritable bowel syndrome; frequent (more than once a week) occurrence of heartburn; or any surgical intervention (e.g., cholecystectomy) which would be expected to influence the absorption of drugs.
• Average daily caffeine intake equivalent to > 4 cups of coffee or > 6 cups of tea.
• Subjects who are left handed.