A Repeat Dose Study With GSK1018921 to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics in Healthy Volunteers and Patients With Schizophrenia and to Evaluate Its Effect on PK of Midazolam. (GT1110791)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A 4-Part Parallel Group, Randomized, Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Repeat Doses of GSK1018921 in Healthy Volunteers and Stable Patients With Schizophrenia and to Evaluate Its Effects on Pharmacokinetics of Midazolam.|
- Part A: Safety and tolerability endpoints consisting of: adverse events; 12-lead ECG; vital signs, clinical laboratory evaluations and PK parameters. [ Time Frame: 14 days twice daily dosing. ] [ Designated as safety issue: No ]
- Part B: Midazolam PK following single and repeat doses of GSK1018921. [ Time Frame: 14 days twice daily dosing. ] [ Designated as safety issue: No ]
- Part C: Plasma & CSF glycine concentrations following single doses og GSK1018921. [ Time Frame: After single dosing. ] [ Designated as safety issue: No ]
- Part D: Safety and tolerability endpoints consisting of: adverse events; 12-lead ECG; vital signs, clinical laboratory evaluations and movement scales Simpson Angus Scale, AIMS and Barnes akathisia Scale. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
- Part A: Effects of GSK1018921 on VAS [ Time Frame: 14 days. ] [ Designated as safety issue: No ]
- Part B: None [ Time Frame: 0 ] [ Designated as safety issue: No ]
- Part C: GSK1018921 plasma exposure-CSF glycine relationship [ Time Frame: After single dosing. ] [ Designated as safety issue: No ]
- Part D: Effects of GSK1018921 on VAS, PANSS and CGI [ Time Frame: 28 days. ] [ Designated as safety issue: No ]
|Study Start Date:||July 2008|
|Study Completion Date:||March 2009|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
Glycine Transporter-1 inhibitor to modulate the NMDA receptor.
Drug: Glycine Transporter-1 inhibitor
GSK1018921 is a potent and selective inhibitor of the glycine transporter-1 (GlyT-1).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00929370
|United States, California|
|GSK Investigational Site|
|Glendale, California, United States, 91206|
|United States, Texas|
|GSK Investigational Site|
|Bellaire, Texas, United States, 77401|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|