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.

Schizophrenia Clinical Trial

— GT1110791  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00929370
• Other study ID #: 110791
• Status: Terminated
• Phase: Phase 1
• First received: June 25, 2009
• Last updated: June 25, 2009
• Start date: July 2008
• Est. completion date: March 2009

Study information

• Verified date: June 2009
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: March 2009
• Est. primary completion date: October 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Glycine Transporter-1 inhibitor
GSK1018921 is a potent and selective inhibitor of the glycine transporter-1 (GlyT-1).

Locations

Country	Name	City	State
United States	GSK Investigational Site	Bellaire	Texas
United States	GSK Investigational Site	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Safety and tolerability endpoints consisting of: adverse events; 12-lead ECG; vital signs, clinical laboratory evaluations and PK parameters.		14 days twice daily dosing.	No
Primary	Part B: Midazolam PK following single and repeat doses of GSK1018921.		14 days twice daily dosing.	No
Primary	Part C: Plasma & CSF glycine concentrations following single doses og GSK1018921.		After single dosing.	No
Primary	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.		28 days	No
Secondary	Part A: Effects of GSK1018921 on VAS		14 days.	No
Secondary	Part B: None		0	No
Secondary	Part C: GSK1018921 plasma exposure-CSF glycine relationship		After single dosing.	No
Secondary	Part D: Effects of GSK1018921 on VAS, PANSS and CGI		28 days.	No