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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00929370
Recruitment Status : 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.)
First Posted : June 29, 2009
Last Update Posted : June 29, 2009
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Glycine Transporter-1 inhibitor Phase 1

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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.
Study Start Date : July 2008
Actual Primary Completion Date : October 2008
Actual Study Completion Date : March 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
U.S. FDA Resources

Arm Intervention/treatment
Experimental: GSK1018921
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).

Primary Outcome Measures :
  1. 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. ]
  2. Part B: Midazolam PK following single and repeat doses of GSK1018921. [ Time Frame: 14 days twice daily dosing. ]
  3. Part C: Plasma & CSF glycine concentrations following single doses og GSK1018921. [ Time Frame: After single dosing. ]
  4. 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 ]

Secondary Outcome Measures :
  1. Part A: Effects of GSK1018921 on VAS [ Time Frame: 14 days. ]
  2. Part B: None [ Time Frame: 0 ]
  3. Part C: GSK1018921 plasma exposure-CSF glycine relationship [ Time Frame: After single dosing. ]
  4. Part D: Effects of GSK1018921 on VAS, PANSS and CGI [ Time Frame: 28 days. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00929370

United States, California
GSK Investigational Site
Glendale, California, United States, 91206
United States, Texas
GSK Investigational Site
Bellaire, Texas, United States, 77401
Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: Study Director, GSK Identifier: NCT00929370     History of Changes
Other Study ID Numbers: 110791
First Posted: June 29, 2009    Key Record Dates
Last Update Posted: June 29, 2009
Last Verified: June 2009

Keywords provided by GlaxoSmithKline:
GlyT-1 inhibitor
Healthy Volunteers

Additional relevant MeSH terms:
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Glycine Agents