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SB-480848

Phase 2

Atherosclerosis | Small molecule | Cardiovascular |GSK plc|Last Updated: Mar 20, 2018

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
RandomizedDouble-BlindPLACEBO_CONTROLLEDBiomarker
Total Trials6
Total Enrollment1,495
FDA Designations
No designations recorded
Clinical Trials (6)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00268996Integrated Biomarker And Imaging Study - 2PHASE2 COMPLETED 336Nov 10, 2005Aug 28, 2007Mar 20, 201826 Austria, Belgium +9
NCT00269048SB-480848 In Subjects With Coronary Heart DiseasePHASE2 COMPLETED 969Nov 1, 2005Sep 1, 2006Aug 8, 2016119 United States, Argentina +14
NCT01916720Study to Determine the Effect of 14 Days Dosing With Darapladib (SB-480848) on Carotid Plague Composition in Patients With Planned Carotid EndarterectomyPHASE2 COMPLETED 103Jan 1, 2003Jul 1, 2003Dec 5, 2016 -
NCT00704431A Study With Darapladib to Collect Tolerability InformationPHASE1 COMPLETED 2May 1, 2008Oct 1, 2008Nov 4, 20161 United States
NCT00622830Phase I Study of SB-480848(Darapladib) -Repeat Dose Study in Healthy Japanese Male Subjects-PHASE1 COMPLETED 18Jan 1, 2008Mar 1, 2008Nov 3, 20161 Japan
NCT00368576A Study To Determine The Effect Of SB-480848 On AsthmaPHASE1 COMPLETED 67Aug 1, 2006Oct 1, 2007Dec 5, 20167 United States, Germany
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Study Endpoints
Primary Endpoints
Mean Circulating High Sensitivity C- Reactive Protein (Hs-CRP) Levels at Week 52.
Week 52

hs-CRP is a pentameric protein that is rapidly upregulated in response to inflammation and tissue damage and assessed as circulating biomarkers associated with atherosclerosis and cardiovascular risk. Last Observation Carried Forward (LOCF) data was reported. Only data from 3 months onwards was carried forward. hs-CRP has a skewed distribution and values were log transformed before analysis. The statistics was calculated on the log transformed data and back transformed. The adjusted geometric means of hs-CRP levels at Week 52 were reported. The levels were analyzed using analysis of co-variance (ANCOVA), with Acute Coronary Syndrome (ACS) status, pooled country and treatment included as covariates.

Change From Baseline in the Density of Rotterdam Classification (ROC) Grade III/IV Strain Spots/10 Millimeter (mm) Within the Region of Interest (ROI) on IVUS Grey Scale Based Palpography at the End of Week 52.
Baseline and Week 52

The ROC grade III/IV strain spots per 10 millimetre (mm) within the ROI on intravascular ultrasound (IVUS) grey scale based palpography were assessed and change from Baseline at end of 52 was reported. Change from Baseline was calculated as the density of spots at the end of study minus the density of spots recorded at Baseline. If either value was considered missing then the change from Baseline value was missing for the participant. Between treatment group comparisons of change from Baseline were analyzed using ANCOVA adjusting for ACS status, pooled country, Baseline value, matched segment length and treatment. Adjusted means and associated standard errors for each treatment group were presented. The baseline value for each participant was defined as the last value prior to the first dose of study drug.

On treatment sustained inhibition of plasma Lp-PLA2 activity.
12 Weeks
Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy
14 +/- 4 days
Adverse events as reported by subjects.
From dosing through to follow-up visit.
Safety/tolerability of repeat oral doses of darapladib
Primary Pharmacokinetic parameters of repeat oral doses of darapladib
FEV1
6 hours post-dose, Days 7, 14 and 21
Secondary Endpoints
Circulating Hs-CRP at the End of Week 26.
Week 26
Mean Lipoprotein Phospholipase A2 (Lp-PLA2) Activity at the End of Week 26 and Week 52
Week 26 and Week 52
Change From Baseline in Plaque Volume as IVUS-Grey Scale Assessments at Week 52
Baseline and Week 52
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Subjects with ACS and evidence of MN:SB-480848EXPERIMENTALEnrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive 160mg of SB-480848 once daily with food for 52 weeks
Subjects with ACS and evidence of MN: placeboPLACEBO_COMPARATOREnrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive SB-480848 matching placebo once daily with food for 52 weeks
Non-ACS and ACS subjects without evidence of MN: SB-480848EXPERIMENTALEnrolled subjects (non-ACS subjects and those ACS subjects without evidence of myocardial necrosis) will receive 160mg of SB-480848 once daily with food for 52 weeks
Non-ACS and those ACS subjects without evidence of MN: placeboPLACEBO_COMPARATOREnrolled subjects (non-ACS subjects and those ACS subjects without evidence of myocardial necrosis) will receive SB-480848 matching placebo once daily with food for 52 weeks
Arm 1EXPERIMENTALSB-480848
Arm 2PLACEBO_COMPARATORplacebo
SB-480848 40 mgEXPERIMENTALSB-480848 40 milligrams (mg) once a day (od) for 14 +/- 4 days followed by carotid endarterectomy. SB-480848 40 mg was administered as 2 SB-480848 20 mg tablets plus 2 placebo tablets.
SB-480848 80 mgEXPERIMENTALSB-480848 80 mg od for 14 +/- 4 days followed by carotid endarterectomy.SB-480848 80 mg was administered as 4 20 mg SB-480848 tablets.
Matching PlaceboPLACEBO_COMPARATORPlacebo for 14 +/- 4 days followed by carotid endarterectomy. Placebo was administered as 4 placebo tablets. Placebo tablets were identical in appearance to the SB-480848 20 mg tablets.
darapladibEXPERIMENTALdarapladib
Interventions
NameTypeDescription
SB-480848DRUGSB-480848 is available as enteric-coated, free-base micronized tablet
SB-480848 matching placeboDRUGPlacebo is available as enteric-coated, free-base micronized tablet
placeboDRUGplacebo
SB-480848 40 mgDRUGStudy Drug
SB-480848 80 mgDRUGStudy Drug
SB-480848 (darapladib)DRUG160 mg darapladib
SB 480848, tabletsDRUG -
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Eligibility Criteria
Age Range18 Years — 80 Years
SexALL
Healthy VolunteersNo
Study Sites26

Inclusion criteria: * Successful PCI (Percutaneous Coronary Intervention) or uncomplicated diagnostic catheterization * Suitable non-intervened coronary artery with IVUS * Antiplatelet therapy Exclusion criteria: * Clinical instability * Previous CABG (Coronary Artery By-pass Graft) surgery * Pla...

Countries:AustriaBelgiumCzechiaDenmarkFranceGermanyNetherlandsNorwayPolandSpainSwitzerlandUnited StatesArgentinaAustraliaBulgariaCanadaEstoniaHungaryIndiaNew ZealandPakistanRomaniaJapan
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