First Time in Human Study With GSK1018921

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: GSK1018921; Drug: Nicotine Lozenges; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Subjects receiving treatment in cohort A; 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; GSK1018921 will be supplied as 0.5, 5, 10 and 40 milligrams coated tablets.; Drug: Nicotine Lozenges; Nicotine Lozenges will be supplied as 4 milligrams lozenges.; Drug: Placebo; Placebo tablets will be given to the subjects.
Experimental: Part A: Subjects receiving treatment in cohort B; 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; GSK1018921 will be supplied as 0.5, 5, 10 and 40 milligrams coated tablets.; Drug: Nicotine Lozenges; Nicotine Lozenges will be supplied as 4 milligrams lozenges.; Drug: Placebo; Placebo tablets will be given to the subjects.
Experimental: Part A: Subjects receiving treatment in cohort C; 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; GSK1018921 will be supplied as 0.5, 5, 10 and 40 milligrams coated tablets.; Drug: Nicotine Lozenges; Nicotine Lozenges will be supplied as 4 milligrams lozenges.; Drug: Placebo; Placebo tablets will be given to the subjects.
Experimental: Part B: Subjects in 5 period crossover period; 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; GSK1018921 will be supplied as 0.5, 5, 10 and 40 milligrams coated tablets.; Drug: Nicotine Lozenges; Nicotine Lozenges will be supplied as 4 milligrams lozenges.; Drug: Placebo; Placebo tablets will be given to the subjects.
Experimental: Part B: Subjects in 4 period crossover period; 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; GSK1018921 will be supplied as 0.5, 5, 10 and 40 milligrams coated tablets.; Drug: Nicotine Lozenges; Nicotine Lozenges will be supplied as 4 milligrams lozenges.; Drug: Placebo; Placebo tablets will be given to the subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2007
• Primary Completion (Actual): July 12, 2008
• Study Completion (Actual): July 12, 2008

Study Registration Dates

• First Submitted: September 6, 2007
• First Submitted That Met QC Criteria: September 6, 2007
• First Posted (Estimate): September 10, 2007

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 3, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: qEEG,; GlyT-1 inhibitor,; ERP; GSK1018921,; FTIH,; schizophrenia,; single-dose,; healthy volunteers,; MMN,
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: GT1109727