Effects of the D3 Antagonist GSK598809 on Food Reward and Reinforcement

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT01039454

Collaborator

(none)

Enrollment

Locations

Arms

16.2

Actual Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This novel compound is a new experimental treatment that may help people to stop compulsive overeating. Compulsive overeating or binge eating is one of the main reasons why people are overweight or obese. Recent research has shown that some kinds of overeating may be linked to a brain chemical called dopamine. There is some evidence that blocking the action of this chemical in animals can reduce food intake, particularly of foods that are high in fat and sugar. The purpose of this study is to find out if this compound (which blocks the effects of dopamine) has the same effect in overweight or obese people, as it does in animals.

Condition or Disease	Intervention/Treatment	Phase
Substance Dependence	Drug: GSK598809 Capsules Drug: GSK598809 Placebo Capsules	Phase 1

Detailed Description

This novel compound is being developed for the treatment of substance dependence and potentially other impulse control disorders.

This is an fMRI study designed to examine the behavioural and physiological effects of a single dose of novel compound on food reward and reinforcement in relation to food seeking behaviour under conditions of fasting, using fMRI, neurocognitive and metabolic endpoints in overweight and obese subjects. These main objectives will be evaluated in the principal part of the study, Part A. The study will also consist of a follow up period of weight management with a dietician where exploratory objectives are considered, Part B.

Part A, will be a single-blind, randomised, placebo controlled, multi-centre, two-period cross-over study. Approximately 24 subjects will be enrolled such that a minimum of 20 subjects complete dosing and critical assessments. All subjects will be required to complete questionnaires, perform a series of behavioural tasks and scanning procedures. Safety and tolerability will be assessed by monitoring subjects for adverse events, vital signs, ECGs, movement disorders (EPS, Akathisia) and laboratory parameters. The pharmacokinetic profile of the compound in this subject population will be determined by blood sampling over a 72 hour period post dosing, in both sessions. Part B will consist of 12 weeks weight management directed by a dietician on an outpatient basis. Subjects will have fortnightly visits with a dietician and at the end of the 12 weeks complete three questionnaires (TFEQ-18R, DBEQ and YBOCS-BE) and have their weight measured to assess weight loss.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Single-blind, Randomized, Placebo Controlled, Two-period Crossover fMRI Study to Investigate the Effects of the D3 Antagonist GSK598809 on Neural and Behavioural Responses to Food Reward and Reinforcement After a Single Oral Dose of GSK598809 in Overweight and Obese Subjects.

Actual Study Start Date :

Dec 18, 2008

Actual Primary Completion Date :

Apr 26, 2010

Actual Study Completion Date :

Apr 26, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 2 way cross over.	Drug: GSK598809 Placebo Capsules Treatment of substance dependence and potentially other impulse control disorders.
Active Comparator: Active 2 Way cross over	Drug: GSK598809 Capsules GSK598809 is being developed for the treatment of substance dependence and potentially other impulse control disorders.

Arm

Intervention/Treatment

Placebo Comparator: Placebo

2 way cross over.

Drug: GSK598809 Placebo Capsules

Treatment of substance dependence and potentially other impulse control disorders.

Active Comparator: Active

2 Way cross over

Drug: GSK598809 Capsules

GSK598809 is being developed for the treatment of substance dependence and potentially other impulse control disorders.

Outcome Measures

Primary Outcome Measures

Functional MRI: Food Processing Task, Food-Stop Signal Task, Food Stroop Task [9 weeks]
Behavioural Neurocognitive Task: Visual Probe Task, Stimulus Response Compatibility Task, Pavlovian-Instrumental Task. [9 weeks]

Secondary Outcome Measures

Appetite VAS, Bond and Lader VAS, Distress VAS, BIS II, TFEQ, BIS/BAS, BDI-II, Body weight, Metabolic markers: plasma leptin, ghrelin, alpa MSH [9 weeks]
PK endpoints: AUC, Cmax, tmax, t1/2 [9 weeks]
Safety and tolerability: adverse events, laboratory values, cardiovascular - blood pressure; heart rate; ECGs, movement disorders, temperature, respiratory rate, serum prolactin, GH and TSH [9 weeks]