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)
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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. |
- 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 ]
| 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 |
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| 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 |
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 Anti-Anxiety Agents Tranquilizing Agents Central Nervous System Depressants |
Physiological Effects of Drugs Psychotropic Drugs Hypnotics and Sedatives Anesthetics, Intravenous Anesthetics, General Anesthetics GABA Modulators GABA Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Glycine Agents |
ClinicalTrials.gov processed this record on May 23, 2013