Healthy Volunteer Positron Emission Tomography (PET) Brain Occupancy Study of a Phosphodiesterase 4 (PDE4) Inhibitor in Huntington's Disease

Study Overview
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Brief Summary
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This study will investigate if a new experimental drug to treat Huntington's Disease gets into the brain. If it does get into the brain the study will explore the relationship between the amount of drug in the brain and the amount of drug in the blood. The study will involve healthy male volunteers.

Detailed Description
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This is an open label, non-randomized, adaptive design PET occupancy study in healthy adult males. The primary aim of this study is to describe the relationship between plasma concentrations and brain PDE4 occupancy of GSK356278 over time. Up to 24 healthy volunteers may be administered single doses of GSK356278 in order to obtain 12 evaluable complete data sets of occupancy estimates. This study will help to optimize the dose selection for future clinical studies with GSK356278.

Official Title
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An Open Label Positron Emission Tomography Study in Healthy Male Subjects to Investigate Brain PDE4 Engagement, Pharmacokinetics and Safety of Single Oral Doses of GSK356278, Using 11C-(R)-Rolipram as a PET Ligand(s)

Conditions
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Huntington Disease

Intervention / Treatment
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* Drug: GSK356278
* Drug: Rolipram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteer, aged 22-55 years. Normal blood pressure, laboratory values, and body mass index Willing to agree to study procedures & contraception requirements Capable of giving written informed consent Exclusion Criteria: Any evidence of disease that would preclude participation in the clinical study (includes sexually transmitted diseases, exessive alcohol consumption, and substance abuse). Previously involved in another clinical trial within 3 months prior to scheduled administration of study drug Smoker Suffers from claustrophobia Any contraindications for MRI scanning (e.g. pacemaker, metal implants or fillings)

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK356278<br>Investigational drug | Drug: GSK356278<br>* Investigational Medicinal Product<br>Drug: Rolipram<br>* Challenge Agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positron Gamma-ray emmision & voxel counts | Brain regions of interest and associated radionuclitide-activity | 60 minutes | 
| systemic plasma concentration | serial sampling: GSK356278 concentration expressed as mass per unit of volume | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure - mm/Hg | Standard clinical pharmacology safety monitoring of vital signs | 24 hours | 
| ECG - 12-Lead & Telemetry | Standard clinical pharmacology safety monitoring | 24 & 72 hours | 
| Heart rate - bpm | Standard clinical pharmacology safety monitoring of vital signs | 72 hours |