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SB-742457

Phase 2

Alzheimer's Disease | Small molecule | Neurology |GSK plc|Last Updated: Jul 27, 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 Trials5
Total Enrollment1,850
FDA Designations
No designations recorded
Clinical Trials (5)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00708552Study of SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer's DiseasePHASE2 COMPLETED 576Jul 4, 2008Mar 9, 2010Jul 27, 201872 Bulgaria, Chile +9
NCT00710684A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's DiseasePHASE2 COMPLETED 682Jul 1, 2008Nov 16, 2010Dec 7, 2017102 United States, Argentina +7
NCT00348192SB-742457 And Donepezil In Alzheimer's DiseasePHASE2 COMPLETED 200May 1, 2006 -Jun 2, 200926 Austria, Bulgaria +6
NCT00224497A Dose Ranging Study To Investigate The Efficacy And Safety Of SB-742457 In Alzheimer's DiseasePHASE2 COMPLETED 380Sep 1, 2005 -Dec 24, 200948 Austria, Bulgaria +11
NCT00551772A Study To Assess The Pharmacokinetics Of SB-742457 Formulated As A Capsule And A Tablet In Healthy Elderly Volunteers.PHASE1 COMPLETED 12Aug 1, 2007 -Dec 25, 20081 United States
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Study Endpoints
Primary Endpoints
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24
Baseline (Week 0) and Week 24

ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a five point scale. The ADAS-Cog total score is the sum of the calculated scores for Questions 1 (Word recall task), 2 (Naming objects and fingers), and 7 (Word recognition task) and the scores recorded on the CRF for Questions 3 to 6 (Commands, Constructional praxis, Ideational praxis, Orientation) and 8 to 11 (Remembering test instructions, Spoken language ability, Word finding difficulty in spontaneous speech, Comprehension). The total score ranges from 0-70 with higher scores indicating greater dysfunction while lower indicates better cognitive function. Baseline was defined as the value at Week 0. Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Clinician's Interview-Based Impression of Change - Plus (CIBIC+) Score at Week 24
Week 24

The CIBIC+ is a rating scale derived from an interview with the participant and caregiver with an independent rater designed to measure several domains of participant function, such as mental/cognitive state, behavior, and functioning. The scores are rated on a scale of 1 to 7 as follows: 1 (marked improvement), 2 (moderately improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (moderately worse) and 7 (markedly worse).

Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24
Baseline(Week 0) and Week 24

The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

Change in cognition and function after 24 weeks.
To characterise pharmacokinetics ( AUC(0-inf) and Cmax ) of SB-742457 from pre-dose to 96 hours following single doses formulated as a capsule and a tablet.
pre-dose to 96 hours
Secondary Endpoints
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24
Baseline (Week 0) and Week 24
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline Mini Mental State Examination [MMSE] Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24
Baseline (Week 0) and Week 24
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline [MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24
Baseline (Week 0) and Week 24
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
SB-742457 - 15mgEXPERIMENTALSB-742457 - 15mg
PlaceboPLACEBO_COMPARATOR -
SB-742457 - 35mgEXPERIMENTALSB-742457 - 35mg
DonepezilACTIVE_COMPARATOR -
DONEPEZIL + SB-742457 15 MGEXPERIMENTALSB-742457 - 15mg added to existing donepezil treatment
DONEPEZIL + PLACEBOPLACEBO_COMPARATORPlacebo added to existing donepezil
DONEPEZIL + SB-742457 35 MGEXPERIMENTALSB-742457 - 35mg added to existing donepezil
Interventions
NameTypeDescription
SB-742457DRUGinvestigational drug
DonepezilDRUGcomparator
PlaceboDRUGcomparator
SB-742457 15mgDRUGSB-742457 - 15mg added to existing donepezil treatment
SB-742457 35mgDRUGSB-742457 - 35mg added to existing donepezil
donepezil 5-10mgDRUGexisting donepezil treatment
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Eligibility Criteria
Age Range50 Years — 85 Years
SexALL
Healthy VolunteersNo
Study Sites72

Inclusion criteria: * Subjects and their caregivers must provide informed consent prior to study entry. * Subjects must have a clinical diagnosis of probable mild-to-moderate Alzheimer's disease with a documented 6-month history of AD symptoms * Subjects must have a regular caregiver who is willing...

Countries:BulgariaChileCzechiaEstoniaGermanyGreeceMexicoPolandRussiaSouth AfricaSouth KoreaUnited StatesArgentinaAustraliaCanadaItalySpainAustriaSlovakiaUnited KingdomCroatiaNew Zealand
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