GSK618334 Repeat Dose Study

Study Overview
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Brief Summary
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The proposed study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of repeated oral doses of GSK618334 in healthy male and female volunteers.

Detailed Description
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GSK618334 strongly binds to dopamine type 3 receptors in the human brain and is being developed as an innovative treatment for substance dependence. This study will evaluate the safety, tolerability, blood concentrations and effect following repeated oral doses of GSK618334 in healthy male and female volunteers. The effect of food on a single oral dose of GSK618334 will also be evaluated. Another portion of this study will investigate dopamine type 3 receptor binding in the human brain by PET scan before and after repeated doses of GSK618334.

Official Title
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A Placebo-controlled, Single Blind, Randomized Two Part Study Toinvestigate the Tolerability, Pharmacokinetics, and brainDopamine D3 Receptor Occupancy of Increasing Repeat Doses ofGSK618334 for up to 21 Days in Healthy Volunteers.

Conditions
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Substance Dependence

Intervention / Treatment
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* Drug: GSK618334 Low Dose
* Drug: GSK618334 PET subjects
* Drug: GSK618334 Medium Dose
* Drug: GSK618334 High Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Males and Females between the ages of 18-50 years old Male and Female subjects must agree to use protocol specified contraceptive methods. Male subjects only in PET parts of the study. Capable of providing written informed consent. Exclusion Criteria: A positive test for Hepatitis B or Hepatitis C within 3 months of screening. Current or chronic history of liver disease, or known liver/bile/gallbladder abnormalities. Personal or family history of heart disease (such as irregular heart beats, a history of sudden unexplained death in a first degree relative, or unexplained fainting). Screening ECG parameters outside the protocol specified parameters. Pulse rate <50 or >100 bpm OR a systolic blood pressure >140 or <95 mmHg OR a diastolic blood pressure >90 or <50 mmHg at screening and/or baseline. Pregnant or lactating females. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden. Significant suicidal risk.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK618334 low Dose<br>GSK618334 Low Dose | Drug: GSK618334 Low Dose<br>* GSK618334 low dose<br>Drug: GSK618334 PET subjects<br>* PET subjects<br>|
| Experimental: GSK618334 Medium Dose<br>GSK618334 medium dose arm | Drug: GSK618334 PET subjects<br>* PET subjects<br>Drug: GSK618334 Medium Dose<br>* Medium Dose<br>|
| Experimental: GSK618334 High Dose<br>GSK618334 High Dose Arm | Drug: GSK618334 PET subjects<br>* PET subjects<br>Drug: GSK618334 High Dose<br>* GSK618334 High Dose<br>|
| Experimental: GSK618334 Placebo<br>Placebo for all 3 dose levels | Drug: GSK618334 Low Dose<br>* GSK618334 low dose<br>Drug: GSK618334 Medium Dose<br>* Medium Dose<br>Drug: GSK618334 High Dose<br>* GSK618334 High Dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability endpoints will be: adverse events, laboratory values, cardiovascular variables (blood pressure, heart rate, ECG), temperature, respiratory rate, assessment of mood and abnormal movements, and GSK618334 blood levels. |  | First dose to follow-up | 
| To assess blood concentrations of GSK618334 after repeated oral doses. |  | First dose to 72 hours post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of food on GSK618334 blood concentrations after a single dose. |  | First dose of the single dose session to 24 hours after dosing of the repeat dose session | 
| The dopamine type 3 receptor binding in the brain (by PET scan) of GSK618334 following the repeat dose session. |  | First dose to 24 hours after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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compulsive discorders, addiction