Clinical trial NCT00929370: 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.
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: Schizophrenia
GSK1018921
GlyT-1 inhibitor
Healthy Volunteers
CSF
Patient
Midazolam
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-06-29
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Part A: Safety and tolerability endpoints consisting of: adverse events; 12-lead ECG; vital signs, clinical laboratory evaluations and PK parameters.
timeFrame: 14 days twice daily dosing.
measure: Part B: Midazolam PK following single and repeat doses of GSK1018921.
timeFrame: 14 days twice daily dosing.
measure: Part C: Plasma & CSF glycine concentrations following single doses og GSK1018921.
timeFrame: After single dosing.
measure: 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.
timeFrame: 28 days
Secondary outcomes:
measure: Part A: Effects of GSK1018921 on VAS
timeFrame: 14 days.
measure: Part B: None
timeFrame: 0
measure: Part C: GSK1018921 plasma exposure-CSF glycine relationship
timeFrame: After single dosing.
measure: Part D: Effects of GSK1018921 on VAS, PANSS and CGI
timeFrame: 28 days.
Other outcomes:
Locations:
city: Glendale
country: United States
facility: GSK Investigational Site
state: California
city: Bellaire
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: