The present study will investigate in humans the enzyme inhibition effects of SB-649868 on CYP3A4, using Simvastatin and Atorvastatin as CYP3A4 probe substrates, administered as single doses: alone, and on two different occasions after repeat doses of SB-649868, at the same time as SB-649868 and 2h before SB-649868.

Inclusion Criteria:

1. Healthy male subject, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, neuropsychiatric status using the MINI International Neuropsychiatric Interview, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. However,

   • Subjects with cTpn I values above 99th percentile of normal range of the selected assay should always be excluded from enrollment;
   • Subjects with alkaline phosphatase or bilirubin > 1.5xULN should always be excluded (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%);

2. Male between 18 and 65 years of age inclusive, at the time of signing the informed consent.

3. Body weight ≥50 kg and BMI within the range 18.5-29.9 kg/m2 inclusive.

4. Subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 3 days post last dose (equivalent to 5 terminal half-lives post-last dose).

5. Having given written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

1. History or presence of significant psychiatric neurological, musculo-skeletal , respiratory, gastrointestinal, hepatic, uncontrolled hypothyroidism. pancreatic or renal diseases or of any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.

2. Subjects, who in the Investigator's judgement, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behaviour and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months.

3. History of cardiovascular diseases and/or evidence of repolarization defects.

4. Family history of heriditary muscular disorders.

5. Subjects with abnormal ECG defined as: average QTcB or QTcF > 450 msec; PQ < 120 ms or > 220 ms; complete left bundle branch block; second-or third-degree AV block; any relevant ST/T wave abnormalities ; any atrial or ventricular arrhtymias which are of clinical significance as determined by the Investigator.

6. History of regular alcohol consumption within 6 months of the study defined as:

   • an average weekly intake of greater than 21 units (14 units for female) or an average daily intake of greater than 3 units (2 units for female). 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.

7. 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 investigator or GSK Medical Monitor, contraindicates their participation.

8. Vulnerable subjects, or subject is mentally or legally incapacitated, or has language barrier precluding adequate understanding of cooperation.

9. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

10. A positive test for HIV antibody.

11. A positive pre-study drug/alcohol screen.

12. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

13. 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, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.

14. Consumption of broccoli, radish sprouts, cauliflower, cabbage, orange juice, apple juice grapefruit juice or grapefruit within 7 days prior to the first dose of study medication until collection of the final pharmacokinetic blood sample.

15. The subject has participated in a clinical trial and has received an investigational product (IP) within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the IP (whichever is longer).

16. Exposure to more than four new chemical entities (i.e., medical drugs being under development) within 12 months prior to the first dosing day.

17. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

18. Unwillingness or inability to follow the procedures outlined in the protocol.

19. The subject is unable or unwilling to abstain from strenuous physical activity in the 48 h before screening and up to the follow up visit.

20. Subject is the investigator or his/her deputies, research assistant, pharmacist, study coordinator, other staff or relative thereof involved in the conduct of the study.

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.