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
  Purpose

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 Intervention Phase
Schizophrenia
Drug: Glycine Transporter-1 inhibitor
Phase 1

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 34
Study Start Date: July 2008
Study Completion Date: March 2009
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00929370

Locations
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
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00929370     History of Changes
Other Study ID Numbers: 110791
Study First Received: June 25, 2009
Last Updated: June 25, 2009
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by GlaxoSmithKline:
Schizophrenia
GSK1018921
GlyT-1 inhibitor
Healthy Volunteers
CSF
Patient
Midazolam

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

ClinicalTrials.gov processed this record on August 18, 2014