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)

This study has been terminated.
(Study has now been terminated due to changes in project strategy. Current available data will be analysed and reported in a synoptic study report.)
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00929370
First received: June 25, 2009
Last updated: NA
Last verified: June 2009
History: No changes posted

June 25, 2009
June 25, 2009
July 2008
October 2008   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
No Changes Posted
  • 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 ]
Same as current
Not Provided
Not Provided
 
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.
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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Schizophrenia
Drug: Glycine Transporter-1 inhibitor
GSK1018921 is a potent and selective inhibitor of the glycine transporter-1 (GlyT-1).
Experimental: GSK1018921
Glycine Transporter-1 inhibitor to modulate the NMDA receptor.
Intervention: Drug: Glycine Transporter-1 inhibitor
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
34
March 2009
October 2008   (final data collection date for primary outcome measure)

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.

Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00929370
110791
Not Provided
Study Director, GSK
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
June 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP