First Time in Human Study With GSK1018921

NCT00527020 | Completed Phase 1

• 1 other identifier: GT1109727
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Keywords

qEEG,; GlyT-1 inhibitor,; ERP; GSK1018921,; FTIH,; schizophrenia,; single-dose,; healthy volunteers,; MMN,

Outcome Measures

Primary Outcomes (1)

• 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.

  pre-dose-8-15days post dose

Secondary Outcomes (1)

• 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

  pre-dose-8-15 days post dose

Study Arms (5)

Part A: Subjects receiving treatment in cohort A

EXPERIMENTAL

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.

Drug: GSK1018921; Drug: Nicotine Lozenges; Drug: Placebo

Part A: Subjects receiving treatment in cohort B

EXPERIMENTAL

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.

Drug: GSK1018921; Drug: Nicotine Lozenges; Drug: Placebo

Part A: Subjects receiving treatment in cohort C

EXPERIMENTAL

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.

Drug: GSK1018921; Drug: Nicotine Lozenges; Drug: Placebo

Part B: Subjects in 5 period crossover period

EXPERIMENTAL

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).

Drug: GSK1018921; Drug: Nicotine Lozenges; Drug: Placebo

Part B: Subjects in 4 period crossover period

EXPERIMENTAL

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.

Drug: GSK1018921; Drug: Nicotine Lozenges; Drug: Placebo

Interventions

GSK1018921 DRUG

GSK1018921 will be supplied as 0.5, 5, 10 and 40 milligrams coated tablets.

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 4 period crossover period; Part B: Subjects in 5 period crossover period

Nicotine Lozenges DRUG

Nicotine Lozenges will be supplied as 4 milligrams lozenges.

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 4 period crossover period; Part B: Subjects in 5 period crossover period

Placebo DRUG

Placebo tablets will be given to the subjects.

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 4 period crossover period; Part B: Subjects in 5 period crossover period

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Berlin, 14050, Germany

Location

Related Publications (1)

• Ouellet D, Sutherland S, Wang T, Griffini P, Murthy V. First-time-in-human study with GSK1018921, a selective GlyT1 inhibitor: relationship between exposure and dizziness. Clin Pharmacol Ther. 2011 Oct;90(4):597-604. doi: 10.1038/clpt.2011.154. Epub 2011 Aug 24.

  PMID: 21866096 BACKGROUND

Related Links

• Results for study GT1109727 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Schizophrenia

Interventions

GSK 1018921; Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2007
• First Posted: September 10, 2007
• Study Start: August 10, 2007
• Primary Completion: July 12, 2008
• Study Completion: July 12, 2008
• Last Updated: August 4, 2017

Record last verified: 2017-08

Locations

DE (1)