ObesityPhase 1NCT00976066
[11C]Carfentanil PET Study of GSK1521498
A Phase 1 study testing Part A Assessing GSK1521498, Part B Assessing GSK1521498 and Part C Assessing Naltrexone in people with Obesity, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Part A Assessing GSK1521498, Part B Assessing GSK1521498 and Part C Assessing Naltrexone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Jun 2009to 7 Dec 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Non-randomized [11C]Carfentanil PET Study in Healthy Male Subjects to Investigate Brain Mu-opioid Receptor Occupancy, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1521498 and Naltrexone.
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.
Read the 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
- Being tested
- Part A Assessing GSK1521498, Part B Assessing GSK1521498, Part C Assessing Naltrexone
- Keywords
- Obesity, Naltrexone, Carfentanil, Receptor Occupancy, mu-opioid Receptor, PET (Positron Emission Tomography), BOLD-fMRI
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part A Assessing GSK1521498Drug
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 GSK1521498Drug
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).
Part C Assessing NaltrexoneDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| GSK1521498 | Experimental | Subjects will receive a dose of the experimental compound GSK1521498 Receives: Drug: Part A Assessing GSK1521498; Drug: Part B Assessing GSK1521498 |
| Naltrexone | Active comparator | Subjects will receive a dose of the licensed pharmaceutical product, Naltrexone Receives: Drug: Part C Assessing Naltrexone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The degree and time-course of mu-opioid receptor occupancy by GSK1521498 in brain regions of interest as measured by PET
Measured: Assessed at various endpoints to be determined based on emerging results
The relationship between plasma concentration and mu-opioid receptor occupancy by GSK1521498
Measured: 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
Measured: 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).
Measured: 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
Measured: 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)
Measured: During fMRI scanning sessions
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2009 (estimated)
- Study start15 Jun 2009
- Primary completion7 Dec 2009
- Study completion7 Dec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00976066
- Sponsor's protocol ID
- 111848
- Status last verified
- Jun 2017
- First submitted
- 11 Sep 2009
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
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.
PubMed 21502953
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-randomized [11C]Carfentanil PET Study in Healthy Male Subjects to Investigate Brain Mu-opioid Receptor Occupancy, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1521498 and Naltrexone.
- ClinicalTrials.gov ID
- NCT00976066
- Acronym / sponsor ID
- 111848
- Conditions
- Obesity
- Keywords
- Obesity, Naltrexone, Carfentanil, Receptor Occupancy, mu-opioid Receptor, PET (Positron Emission Tomography), BOLD-fMRI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 15 Jun 2009 (actual)
- Primary completion
- 7 Dec 2009 (actual)
- Study completion
- 7 Dec 2009 (actual)
- First posted
- 14 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GSK1521498 | Experimental | Drug: Part A Assessing GSK1521498, Drug: Part B Assessing GSK1521498Subjects will receive a dose of the experimental compound GSK1521498 |
| Naltrexone | Active comparator | Drug: Part C Assessing NaltrexoneSubjects will receive a dose of the licensed pharmaceutical product, Naltrexone |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Part A Assessing GSK1521498Each 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. | Drug | GSK1521498 |
| Part B Assessing GSK1521498The 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). | Drug | GSK1521498 |
| Part C Assessing NaltrexoneA 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). | Drug | Naltrexone |
Primary outcome
The degree and time-course of mu-opioid receptor occupancy by GSK1521498 in brain regions of interest as measured by PET
Time frame: Assessed at various endpoints to be determined based on emerging results
The relationship between plasma concentration and mu-opioid receptor occupancy by GSK1521498
Time frame: Assessed at various endpoints to be determined based on emerging results
4 secondary outcomes
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
Time frame: 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).
Time frame: 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
Time frame: 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)
Time frame: During fMRI scanning sessions
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Background: PubMed 21502953Rabiner 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.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 111848 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Part A Assessing GSK1521498, Part B Assessing GSK1521498 and Part C Assessing Naltrexone in people with Obesity, run by GlaxoSmithKline at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The degree and time-course of mu-opioid receptor occupancy by GSK1521498 in brain regions of interest as measured by PET (time frame: Assessed at various endpoints to be determined based on emerging results). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00976066, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2017.