Study has now been terminated due to changes in project strategy. Current available data will be analysed and reported in a synoptic study report.

The purpose of this study is to understand safety and tolerability of the drug GSK1018921 after 14 days of dosing in healthy volunteers and then in patient volunteers.

This is a four part, parallel group, randomised, study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of repeat doses of GSK1018921 in healthy volunteers and stable patients with schizophrenia and to evaluate its effect on pharmacokinetics of midazolam. Part A will evaluate 14 days repeat BID dosing in at least three cohorts of healthy volunteers, to assess safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK1018921. Part B will study the potential drug interaction of GSK1018921 (Maximum Tolerated Dose from Part A) with midazolam with 14 days repeat BID dosing in healthy volunteers and therefore will assess the PK, safety and tolerability. Part C will be a single dose study in healthy volunteers and will include CSF sampling to assess the concentration of GSK1018921 and glycine in CSF with two doses (80 and 200 mg). Part D will study stable patients with schizophrenia, to assess safety, tolerability, PK and PD following 28 days of repeat BID dosing.

Safety assessments will include physical examination, 12-lead ECGs, holter monitoring, vital signs, orthostatic vital signs, visual assessments, and clinical lab test. Tolerability will be assessed by collecting Adverse Events.

PD assessments will include glycine in red blood cells, plasma and CSF, as well as CogState Battery test, Visual Assessment Scale, Positive And Negative Symptom Scores (PANSS) and Clinical Global Impression scales of change.

All subjects (Healthy and Patients)

Exclusion Criteria:

• History of drug or alcohol abuse.
• Consumption of drug, food or drink affecting the CYP450 metabolism pathway.
• Has received investigational drug within 30 days to 5 half lives or twice the duration of the biological effect of any drug (which ever is the longer).
• Donation of blood in excess of 500mL within a 56 day period.

Patients eligibility

- Stable patients with schizophrenia.