An Open Label Positron Emission Tomography (PET) Study of GSK618334 in Healthy Male Subjects Using 11C-PHNO as PET Ligand

An Open Label Positron Emission Tomography Study in Healthy Male Subjects to Investigate Brain Dopamine D3 Receptor Occupancy, Pharmacokinetics and Safety of Single Oral Doses of GSK618334, Using 11C-PHNO as PET Ligand.

The purpose of this study is to investigate the relationship between the plasma concentrations of the study drug and the amount of the study drug bound to the D3 receptors of the brain after dosing of a new compound GSK618334.

Study Overview

• Status: Completed
• Conditions: Substance Dependence
• Intervention / Treatment: Drug: GSK618334

Detailed Description

This imaging study will be an open label, non-randomised PET receptor occupancy study using healthy male volunteers. The time course and degree of D3 receptor occupancy (RO) after single doses of GSK618334 will be determined using 11C-PHNO as a PET ligand labeling dopamine receptor. The PK/PD relationship between plasma concentrations of GSK618334 and D3 RO will be described. Potential relationships between D3 RO and functional magnetic resonance imaging (fMRI) endpoints will be assessed as an exploratory aim.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy, male subjects aged between 30 and 55 old inclusive.
• normal body weight.
• normal ECG and vital signs.
• agree to use acceptable contraceptive methods required.
• capable of giving written informed consent.

Exclusion Criteria:

• smoker or uses other nicotine-containing products.
• certain medical conditions including heart disease, neurological disease, gastrointestinal disease, kidney or liver dysfunction - abnormal laboratory tests.
• certain psychiatric conditions and use of certain psychoactive drugs .
• positive blood alcohol or urine drug test.
• alcohol intake over 14 drinks per week.
• participation in another drug trial within 30 days or a study involving significant radiation exposure.
• donation of more than 450 mL blood within the 56 days.
• family history of cancer (one or more first-degree relative diagnosed before the age of 55 years old).
• having cardiac pacemaker or other electronic device.
• suffers from claustrophobia or feels that he will be unable to lie still on his back in the PET camera.

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: Open-label; D3 receptor antagonist	Drug: GSK618334; D3 receptor antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Binding of PHNO, PET ligand, in each region of interest at each scan.	up to 48 hours
Percentage of PHNO, PET ligand, occupancy in each region of interest after a single oral dose of GSK618334 for each individual.	up to 48 hours
Time course of GSK618334 concentration in blood following a single oral dose.	up to 48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events and other safety assessments such as clinically relevant changes in electrocardiography (ECG); vital signs (blood pressure, heart rate); laboratory safety data and physical examination.	screening to follow-up
Measuring GSK618334 in the body (pharmacokinetic endpoints): PK parameters of GSK618334 Cmax, AUCinf, tmax.	up to 48 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): December 8, 2008
• Primary Completion (Actual): June 11, 2009
• Study Completion (Actual): June 11, 2009

Study Registration Dates

• First Submitted: December 23, 2008
• First Submitted That Met QC Criteria: December 23, 2008
• First Posted (Estimate): December 25, 2008

Study Record Updates

• Last Update Posted (Actual): July 7, 2017
• Last Update Submitted That Met QC Criteria: July 5, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: addiction; positron emission tomography
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: 110269

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. Individual Participant Data Set
   Information identifier: 110269
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 110269
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 110269
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 110269
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 110269
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 110269
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 110269
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register