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Effects of the D3 Antagonist GSK598809 on Food Reward and Reinforcement

Phase 1
Completed
Conditions
Substance Dependence
Interventions
Drug: GSK598809 Placebo Capsules
Drug: GSK598809 Capsules
Registration Number
NCT01039454
Lead Sponsor
GlaxoSmithKline
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria
  • generally healthy
  • right handed
  • binge eating episode
  • use appropriate contraception method
  • willing to see a dietician
  • overweight or obese (BMI 27 - 40 kg/m2)
Exclusion Criteria
  • pregnant or breast feeding female
  • recent weight loss or gain
  • recent use of weight loss drugs
  • surgery for obesity
  • abuse alcohol or drugs
  • cannot do MRI scans
  • smokers
  • certain emotional problems being treated with medications
  • medical, surgical or neuropsychiatric illness
  • ECG abnormality
  • sudden unexplained death or syncope in first degree relatives

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboGSK598809 Placebo Capsules2 way cross over.
ActiveGSK598809 Capsules2 Way cross over
Primary Outcome Measures
NameTimeMethod
Functional MRI: Food Processing Task, Food-Stop Signal Task, Food Stroop Task9 weeks
Behavioural Neurocognitive Task: Visual Probe Task, Stimulus Response Compatibility Task, Pavlovian-Instrumental Task.9 weeks
Secondary Outcome Measures
NameTimeMethod
PK endpoints: AUC, Cmax, tmax, t1/29 weeks
Appetite VAS, Bond and Lader VAS, Distress VAS, BIS II, TFEQ, BIS/BAS, BDI-II, Body weight, Metabolic markers: plasma leptin, ghrelin, alpa MSH9 weeks
Safety and tolerability: adverse events, laboratory values, cardiovascular - blood pressure; heart rate; ECGs, movement disorders, temperature, respiratory rate, serum prolactin, GH and TSH9 weeks

Trial Locations

Locations (1)

GSK Investigational Site

🇬🇧

London, United Kingdom

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