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

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)

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.

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: GSK356278; Drug: Rolipram

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • GSK Investigational Site
  • London, United Kingdom, W12 ONN
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK356278; Investigational drug	Drug: GSK356278; Investigational Medicinal Product; Drug: Rolipram; Challenge Agent

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2011
• Primary Completion (Actual): April 12, 2012
• Study Completion (Actual): April 12, 2012

Study Registration Dates

• First Submitted: December 1, 2011
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (Estimate): May 21, 2012

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: June 19, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Antidepressive Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Rolipram
• Other Study ID Numbers: 116038

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: 116038
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 116038
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 116038
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 116038
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 116038
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 116038
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 116038
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register