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First Time in Human Study With GSK1018921

Primary Purpose

Schizophrenia

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
GSK1018921
Nicotine Lozenges
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring qEEG,, GlyT-1 inhibitor,, ERP, GSK1018921,, FTIH,, schizophrenia,, single-dose,, healthy volunteers,, MMN,

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy volunteers as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring.
  • For Part B, smokers.

Exclusion Criteria:

  • Part A: Smokers, any subject who takes any prescribed or non-prescribed medication/vitamins specified as prohibited in the protocol, substance abuse, clinically significant disease as determined by a responsible physician.
  • Part B: Non-Smokers

Sites / Locations

  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Part A: Subjects receiving treatment in cohort A

Part A: Subjects receiving treatment in cohort B

Part A: Subjects receiving treatment in cohort C

Part B: Subjects in 5 period crossover period

Part B: Subjects in 4 period crossover period

Arm Description

Eligible subjects will be randomized to receive GSK101892 and placebo. Subjects will receive escalated doses of GSK101892 with a starting dose of 0.5 milligrams. Each subject will receive no more than 4 doses of GSK1018921 in a maximum of 5 dosing sessions. Within each cohort, each session will be separated by a washout period of at least 7 days.

Eligible subjects will be randomized to receive GSK101892 and placebo. Subjects will receive escalated doses of GSK101892 with a starting dose of 0.5 milligrams. Each subject will receive no more than 4 doses of GSK1018921 in a maximum of 5 dosing sessions. Within each cohort, each session will be separated by a washout period of at least 7 days.

Eligible subjects will be randomized to receive GSK101892 and placebo. Subjects will receive escalated doses of GSK101892 with a starting dose of 0.5 milligrams. Each subject will receive no more than 4 doses of GSK1018921 in a maximum of 5 dosing sessions. Within each cohort, each session will be separated by a washout period of at least 7 days.

Eligible subjects (first 14 subjects) will be randomized to one of the following 14 sequences as a 5 period crossover with sequences; LMNOQ, MNOLQ, NOLMQ, OLMNQ, ONMLQ, NMLOQ, MLONQ, LONMQ, LNMOQ, NMOLQM MOLNQ, OLNMQ, OMNLQ and MNLOQ) (L= 80 milligrams GSK1018921 given in fasted state, M= 200 milligrams GSK1018921 given in fasted state, N= nicotine lozenge, O= placebo and Q= 80 milligrams GSK1018921 in fed state).

Eligible subjects (last 7 subjects) will be randomized to one of the following 7 sequences as a 4 period crossover with sequences; NLOM, LOMN, OLNM, LNMO, NMOL, MOLN, and MNLO.

Outcomes

Primary Outcome Measures

Part A:Safety pre-dose-8-15days post dose Tolerability,PK of single escalating doses. Part B: PD effects of single doses of GSK1018921 and nicotine on Quantitative Electroencephalography and MisMatch Negativity in smokers.

Secondary Outcome Measures

Part A:Characterise single-dose PD with Bond-Lader Visual analogue Scale,Profile of Mood State,Glycine levels.Part B:Safety pre-dose-8-15 days post dose,Tolerability,PK of single escalating doses.Amplitude and latency of P300, Effects on P50 suppression

Full Information

First Posted
September 6, 2007
Last Updated
August 3, 2017
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00527020
Brief Title
First Time in Human Study With GSK1018921
Official Title
Single-Blind, Randomised, Placebo-controlled First Time in Human Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Oral Escalating Doses of GSK1018921 in Healty Volunteers and a Randomized, Double-blind, Double Dummy, Placebo Controlled, Three-way Crossover Study in a Separate Cohort of Healthy Volunteers to Test the Effect of Single Doses of GSK1018921 and Nicotine on qEEG and MMN in Healthy Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
August 10, 2007 (Actual)
Primary Completion Date
July 12, 2008 (Actual)
Study Completion Date
July 12, 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
GSK1018921 is a new drug under development for the treatment of schizophrenia. GSK1018921 differs from other available drugs in its mode of action and it is assumed that it may have an effect in the treatment of so-called positive symptoms such as hallucinations and negative symptoms such as lack of drive. No clinical studies have been conducted with GSK1018921 in humans until now. This is the first study where this compound is administered to humans; the study has 2 parts: Part A is a dose escalation study, Part B is a pharmacodynamic portion in a separate group of healthy smoker volunteers.
Detailed Description
Single-Blind, Randomised, Placebo-Controlled First Time in Human Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Oral Escalating Doses of GSK1018921 in Healthy Volunteers and to assess the effect of a single dose of GSK1018921 on quantitative EEG and Mismatch Negativity in a separate cohort of healthy smoker volunteers

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
qEEG,, GlyT-1 inhibitor,, ERP, GSK1018921,, FTIH,, schizophrenia,, single-dose,, healthy volunteers,, MMN,

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A: Subjects receiving treatment in cohort A
Arm Type
Experimental
Arm Description
Eligible subjects will be randomized to receive GSK101892 and placebo. Subjects will receive escalated doses of GSK101892 with a starting dose of 0.5 milligrams. Each subject will receive no more than 4 doses of GSK1018921 in a maximum of 5 dosing sessions. Within each cohort, each session will be separated by a washout period of at least 7 days.
Arm Title
Part A: Subjects receiving treatment in cohort B
Arm Type
Experimental
Arm Description
Eligible subjects will be randomized to receive GSK101892 and placebo. Subjects will receive escalated doses of GSK101892 with a starting dose of 0.5 milligrams. Each subject will receive no more than 4 doses of GSK1018921 in a maximum of 5 dosing sessions. Within each cohort, each session will be separated by a washout period of at least 7 days.
Arm Title
Part A: Subjects receiving treatment in cohort C
Arm Type
Experimental
Arm Description
Eligible subjects will be randomized to receive GSK101892 and placebo. Subjects will receive escalated doses of GSK101892 with a starting dose of 0.5 milligrams. Each subject will receive no more than 4 doses of GSK1018921 in a maximum of 5 dosing sessions. Within each cohort, each session will be separated by a washout period of at least 7 days.
Arm Title
Part B: Subjects in 5 period crossover period
Arm Type
Experimental
Arm Description
Eligible subjects (first 14 subjects) will be randomized to one of the following 14 sequences as a 5 period crossover with sequences; LMNOQ, MNOLQ, NOLMQ, OLMNQ, ONMLQ, NMLOQ, MLONQ, LONMQ, LNMOQ, NMOLQM MOLNQ, OLNMQ, OMNLQ and MNLOQ) (L= 80 milligrams GSK1018921 given in fasted state, M= 200 milligrams GSK1018921 given in fasted state, N= nicotine lozenge, O= placebo and Q= 80 milligrams GSK1018921 in fed state).
Arm Title
Part B: Subjects in 4 period crossover period
Arm Type
Experimental
Arm Description
Eligible subjects (last 7 subjects) will be randomized to one of the following 7 sequences as a 4 period crossover with sequences; NLOM, LOMN, OLNM, LNMO, NMOL, MOLN, and MNLO.
Intervention Type
Drug
Intervention Name(s)
GSK1018921
Intervention Description
GSK1018921 will be supplied as 0.5, 5, 10 and 40 milligrams coated tablets.
Intervention Type
Drug
Intervention Name(s)
Nicotine Lozenges
Intervention Description
Nicotine Lozenges will be supplied as 4 milligrams lozenges.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets will be given to the subjects.
Primary Outcome Measure Information:
Title
Part A:Safety pre-dose-8-15days post dose Tolerability,PK of single escalating doses. Part B: PD effects of single doses of GSK1018921 and nicotine on Quantitative Electroencephalography and MisMatch Negativity in smokers.
Time Frame
pre-dose-8-15days post dose
Secondary Outcome Measure Information:
Title
Part A:Characterise single-dose PD with Bond-Lader Visual analogue Scale,Profile of Mood State,Glycine levels.Part B:Safety pre-dose-8-15 days post dose,Tolerability,PK of single escalating doses.Amplitude and latency of P300, Effects on P50 suppression
Time Frame
pre-dose-8-15 days post dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy volunteers as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring. For Part B, smokers. Exclusion Criteria: Part A: Smokers, any subject who takes any prescribed or non-prescribed medication/vitamins specified as prohibited in the protocol, substance abuse, clinically significant disease as determined by a responsible physician. Part B: Non-Smokers
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
14050
Country
Germany

12. IPD Sharing Statement

Citations:
Citation
Daniele Ouellet, Suzanne Sutherland, Tianli Wang, Patrizia Griffini, Venkatesha Murthy. First-Time-in-Human Study with GSK1018921, a Selective GlyT1-Inhibitor: Characterization of the Exposure-Response to Dizziness, the Dose Limiting Adverse Event. [Clin Pharmacol Ther]. 2011;DOI: CLPT.2011.154:
Results Reference
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First Time in Human Study With GSK1018921

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