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Part A Assessing GSK1521498

Phase 1

Obesity | Small molecule | Metabolic |GSK plc|Last Updated: Jun 20, 2017

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
ACTIVE_CONTROLLEDBiomarker
Total Trials1
Total Enrollment26
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00976066[11C]Carfentanil PET Study of GSK1521498PHASE1 COMPLETED 26Jun 15, 2009Dec 7, 2009Jun 20, 20171 United Kingdom
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Study Endpoints
Primary Endpoints
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 Endpoints
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
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeBASIC_SCIENCE
Treatment Arms
ArmTypeDescription
GSK1521498EXPERIMENTALSubjects will receive a dose of the experimental compound GSK1521498
NaltrexoneACTIVE_COMPARATORSubjects will receive a dose of the licensed pharmaceutical product, Naltrexone
Interventions
NameTypeDescription
Part A Assessing GSK1521498DRUGEach 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 GSK1521498DRUGThe 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 NaltrexoneDRUGA 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).
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Eligibility Criteria
Age Range25 Years — 65 Years
SexMALE
Healthy VolunteersYes
Study Sites1

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 ob...

Countries:United Kingdom
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