[11C]Carfentanil PET Study of GSK1521498

This imaging study will be an open-label, non-randomised PET receptor occupancy study in healthy male volunteers. The degree and time course of μ-opioid receptor occupancy (RO) following single oral doses of GSK1521498 will be estimated by [11C]carfentanil displacement. Previous pre-clinical and human PET studies indicate that [11C]carfentanil is selective for the μ-opioid receptor and can be used to estimate μ-opioid receptor occupancy in vivo.

The PK/PD relationship between plasma concentrations of GSK1521498 and μ-opioid RO will be described. Potential relationships between μ-opioid RO and functional magnetic resonance imaging (fMRI) endpoints, measured in a food reward paradigm, will be assessed as an exploratory aim. Additionally, the PK/PD relationships between plasma concentrations of naltrexone (a generic μ-opioid receptor antagonist), μ-opioid receptor occupancy, and fMRI measures of reward processing will also be investigated.

Inclusion criteria

• Healthy male subjects aged between 25 and 65 years old inclusive.
• Body weight ≥ 50 kg and BMI within the range 18.5.0 - 30.0 kg/m2 (inclusive).
• Normal ECG.
• The subject is able to read, comprehend and record information.
• A signed and dated written informed consent is obtained from the subject.
• Compliance with birth control methods as described in the study protocol.

Exclusion criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• The subject has a positive pre-study drug/alcohol screen.
• History of hepatitis B and /or C
• A positive result for an HIV test.
• Abnormal thyroid function
• Positive evaluation for depression.
• History of heavy alcohol use as described in the study protocol.
• The subject has participated in a clinical trial and has received an investigational product within: 90 days.
• Participation in other drug studies within a calendar year.
• Use of prohibited medications as described in the study protocol.
• History of sensitivity to any of the study medications.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Past or present use of tobacco products.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
• Previous radiation dosages in excess of levels acceptable to take part in this study.
• History of claustrophobia or history of neurological conditions.
• Presence of a cardiac pacemaker.
• Works as a welder, metal worker or machinist