[11C]Carfentanil PET Study of GSK1521498

NCT00976066 | Completed Phase 1

• 1 other identifier: 111848
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity

Keywords

Obesity; Naltrexone; Carfentanil; Receptor Occupancy; mu-opioid Receptor; PET (Positron Emission Tomography); BOLD-fMRI

Outcome Measures

Primary Outcomes (2)

• The degree and time-course of mu-opioid receptor occupancy by GSK1521498 in brain regions of interest as measured by PET

  Assessed at various endpoints to be determined based on emerging results

• The relationship between plasma concentration and mu-opioid receptor occupancy by GSK1521498

  Assessed at various endpoints to be determined based on emerging results

Secondary Outcomes (4)

• Adverse events and clinically relevant changes in electrocardiography (ECG); vital signs (blood pressure, heart rate); POMS, Bond and Lader VAS, laboratory safety data and physical examination

  Duration of study

• Pharmacokinetic endpoints will be: AUC(0-∞), AUC(0-t), maximum observed plasma drug concentration (Cmax), time to maximum observed plasma drug concentration (Tmax), terminal elimination half-life (t½).

  PK samples will be collected throughout the study

• The degree and time-course of mu-opioid receptor occupancy by naltrexone in brain regions of interest as measured by PET

  Assessed at various endpoints to be determined based on emerging results

• The relationship between mu-opioid receptor occupancy by GSK1521498 and naltrexone and fMRI responses during expectation and receipt of a pleasant tasting reward (juice)

  During fMRI scanning sessions

Study Arms (2)

GSK1521498

EXPERIMENTAL

Subjects will receive a dose of the experimental compound GSK1521498

Drug: Part A Assessing GSK1521498; Drug: Part B Assessing GSK1521498

Naltrexone

ACTIVE COMPARATOR

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

Drug: Part C Assessing Naltrexone

Interventions

Part A Assessing GSK1521498 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.

GSK1521498

Part B Assessing GSK1521498 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).

GSK1521498

Part C Assessing Naltrexone 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).

Naltrexone

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 21502953 BACKGROUND

Related 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.
• Results for study 111848 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2009
• First Posted: September 14, 2009
• Study Start: June 15, 2009
• Primary Completion: December 7, 2009
• Study Completion: December 7, 2009
• Last Updated: June 20, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)