[11C]Carfentanil PET Study of GSK1521498

NCT ID: NCT00976066

Last Updated: 2017-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-15
• Study Completion Date: 2009-12-07

Brief Summary

The purpose of this study is to determine whether GSK1521498 attaches to sites in the brain called mu-opioid receptors that are involved in the liking reactions to palatable high fat and high sugar foods. We hope that blocking these receptors may modify certain behaviours that may lead to obesity.

Detailed Description

This imaging study will be an open-label, non-randomised PET receptor occupancy study in healthy male volunteers. The degree and time course of μ-opioid receptor occupancy (RO) following single oral doses of GSK1521498 will be estimated by [11C]carfentanil displacement. Previous pre-clinical and human PET studies indicate that [11C]carfentanil is selective for the μ-opioid receptor and can be used to estimate μ-opioid receptor occupancy in vivo.

The PK/PD relationship between plasma concentrations of GSK1521498 and μ-opioid RO will be described. Potential relationships between μ-opioid RO and functional magnetic resonance imaging (fMRI) endpoints, measured in a food reward paradigm, will be assessed as an exploratory aim. Additionally, the PK/PD relationships between plasma concentrations of naltrexone (a generic μ-opioid receptor antagonist), μ-opioid receptor occupancy, and fMRI measures of reward processing will also be investigated.

Conditions

Obesity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

GSK1521498

Subjects will receive a dose of the experimental compound GSK1521498

Group Type: EXPERIMENTAL

Part A Assessing GSK1521498

Intervention Type: DRUG

Each participant will receive up to three [11C]carfentanil PET scans and up to two doses of GSK1521498 in total. The doses used will span the expected receptor occupancy range providing these were well tolerated in the first-time in human study.

Each subject will receive baseline [11C]carfentanil PET and fMRI scans (PET Scan 1 and fMRI Scan 1, respectively), followed by two treatment sessions (Treatment Sessions 1 and 2). Treatment session 1 and 2 are followed by PET scans and an fMRI scan (session 1 only). Sessions will be separated by at least 12 days. PET scans will be timed to coincide with peak brain occupancy. fMRI will begin approximately 30-60 minutes after completion of the PET scan.

Part B Assessing GSK1521498

Intervention Type: DRUG

The purpose of Part B is to establish the timecourse of receptor occupancy of GSK1521498. Each participant in Part B will receive up to three [11C]carfentanil PET scans and one single oral dose of GSK1521498 expected to provide 50-75% receptor occupancy (selected with reference to data from Part A).

Each Part B subject will receive baseline [11C]carfentanil PET and fMRI scans (PET Scan 1 and fMRI Scan 1, respectively) followed by a single treatment session. The treatment session will consist of a single oral dose of GSK1521498 followed by two subsequent PET scans (PET Scans 2 and 3) and one fMRI scan (fMRI Scan 2).

Naltrexone

Subjects will receive a dose of the licensed pharmaceutical product, Naltrexone

Group Type: ACTIVE_COMPARATOR

Part C Assessing Naltrexone

Intervention Type: DRUG

A range of doses of naltrexone will be tested in up to 12 participants in an adaptive design. Each Part C participant will receive up to three \[11C\]carfentanil PET scans and a single oral dose of naltrexone. No dose of naltrexone will exceed 50 mg, the dose usually used therapeutically in the treatment of opiate and alcohol dependence. Each Part C subject will receive baseline \[11C\]carfentanil PET and fMRI scans (PET Scan 1 and fMRI Scan 1, respectively) followed by a single treatment session. The treatment session will consist of a single oral dose of naltrexone followed by two subsequent PET scans (PET Scans 2 and 3) and one fMRI scan (fMRI Scan 2).

Interventions

Part A Assessing GSK1521498

Each participant will receive up to three [11C]carfentanil PET scans and up to two doses of GSK1521498 in total. The doses used will span the expected receptor occupancy range providing these were well tolerated in the first-time in human study.

Each subject will receive baseline [11C]carfentanil PET and fMRI scans (PET Scan 1 and fMRI Scan 1, respectively), followed by two treatment sessions (Treatment Sessions 1 and 2). Treatment session 1 and 2 are followed by PET scans and an fMRI scan (session 1 only). Sessions will be separated by at least 12 days. PET scans will be timed to coincide with peak brain occupancy. fMRI will begin approximately 30-60 minutes after completion of the PET scan.

Intervention Type: DRUG

Part B Assessing GSK1521498

The purpose of Part B is to establish the timecourse of receptor occupancy of GSK1521498. Each participant in Part B will receive up to three [11C]carfentanil PET scans and one single oral dose of GSK1521498 expected to provide 50-75% receptor occupancy (selected with reference to data from Part A).

Each Part B subject will receive baseline [11C]carfentanil PET and fMRI scans (PET Scan 1 and fMRI Scan 1, respectively) followed by a single treatment session. The treatment session will consist of a single oral dose of GSK1521498 followed by two subsequent PET scans (PET Scans 2 and 3) and one fMRI scan (fMRI Scan 2).

Intervention Type: DRUG

Part C Assessing Naltrexone

A range of doses of naltrexone will be tested in up to 12 participants in an adaptive design. Each Part C participant will receive up to three \[11C\]carfentanil PET scans and a single oral dose of naltrexone. No dose of naltrexone will exceed 50 mg, the dose usually used therapeutically in the treatment of opiate and alcohol dependence. Each Part C subject will receive baseline \[11C\]carfentanil PET and fMRI scans (PET Scan 1 and fMRI Scan 1, respectively) followed by a single treatment session. The treatment session will consist of a single oral dose of naltrexone followed by two subsequent PET scans (PET Scans 2 and 3) and one fMRI scan (fMRI Scan 2).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male subjects aged between 25 and 65 years old inclusive.
• Body weight ≥ 50 kg and BMI within the range 18.5.0 - 30.0 kg/m2 (inclusive).
• Normal ECG.
• The subject is able to read, comprehend and record information.
• A signed and dated written informed consent is obtained from the subject.
• Compliance with birth control methods as described in the study protocol.

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• The subject has a positive pre-study drug/alcohol screen.
• History of hepatitis B and /or C
• A positive result for an HIV test.
• Abnormal thyroid function
• Positive evaluation for depression.
• History of heavy alcohol use as described in the study protocol.
• The subject has participated in a clinical trial and has received an investigational product within: 90 days.
• Participation in other drug studies within a calendar year.
• Use of prohibited medications as described in the study protocol.
• History of sensitivity to any of the study medications.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Past or present use of tobacco products.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
• Previous radiation dosages in excess of levels acceptable to take part in this study.
• History of claustrophobia or history of neurological conditions.
• Presence of a cardiac pacemaker.
• Works as a welder, metal worker or machinist

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

London, , United Kingdom

Countries

United Kingdom

References

Rabiner EA, Beaver J, Makwana A, Searle G, Long C, Nathan PJ, Newbould RD, Howard J, Miller SR, Bush MA, Hill S, Reiley R, Passchier J, Gunn RN, Matthews PM, Bullmore ET. Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans. Mol Psychiatry. 2011 Aug;16(8):826-35, 785. doi: 10.1038/mp.2011.29. Epub 2011 Apr 19.

Reference Type: BACKGROUND

PMID: 21502953 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

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Other Identifiers

111848

Identifier Type: -

Identifier Source: org_study_id