GSK618334 Repeat Dose Study

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.

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

Study Overview

• Status: Completed
• Conditions: Substance Dependence
• Intervention / Treatment: Drug: GSK618334 Low Dose; Drug: GSK618334 PET subjects; Drug: GSK618334 Medium Dose; Drug: GSK618334 High Dose

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GSK618334 low Dose; GSK618334 Low Dose	Drug: GSK618334 Low Dose; GSK618334 low dose; Drug: GSK618334 PET subjects; PET subjects
EXPERIMENTAL: GSK618334 Medium Dose; GSK618334 medium dose arm	Drug: GSK618334 PET subjects; PET subjects; Drug: GSK618334 Medium Dose; Medium Dose
EXPERIMENTAL: GSK618334 High Dose; GSK618334 High Dose Arm	Drug: GSK618334 PET subjects; PET subjects; Drug: GSK618334 High Dose; GSK618334 High Dose
EXPERIMENTAL: GSK618334 Placebo; Placebo for all 3 dose levels	Drug: GSK618334 Low Dose; GSK618334 low dose; Drug: GSK618334 Medium Dose; Medium Dose; Drug: GSK618334 High Dose; GSK618334 High Dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

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): September 28, 2009
• Primary Completion (ACTUAL): February 17, 2010
• Study Completion (ACTUAL): February 17, 2010

Study Registration Dates

• First Submitted: December 17, 2009
• First Submitted That Met QC Criteria: December 17, 2009
• First Posted (ESTIMATE): December 21, 2009

Study Record Updates

• Last Update Posted (ACTUAL): June 22, 2017
• Last Update Submitted That Met QC Criteria: June 21, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: addiction; compulsive discorders
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: 108414

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. Statistical Analysis Plan
   Information identifier: 108414
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 108414
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 108414
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 108414
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 108414
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 108414
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register