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SB-742457

Phase 2

Alzheimer's Disease | Small molecule | Neurology |GSK plc|Last Updated: Jul 27, 2018

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials5
Total Enrollment1,850

FDA Designations

No designations recorded

Clinical trial landscape

SB-742457 · 5 trials · 1 indication

Phase 2 4Phase 1 1
NCT00708552Study of SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer's DiseaseAlzheimer's Disease
COMPLETED576 Analytics
NCT00710684A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's DiseaseAlzheimer's Disease
COMPLETED682 Analytics
NCT00348192SB-742457 And Donepezil In Alzheimer's DiseaseAlzheimer's Disease
COMPLETED200 Analytics
NCT00224497A Dose Ranging Study To Investigate The Efficacy And Safety Of SB-742457 In Alzheimer's DiseaseAlzheimer's Disease
COMPLETED380 Analytics
PHASE2COMPLETED
Study of SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer's Disease
Alzheimer's DiseaseUnlock trial analytics
PHASE2COMPLETED
A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's Disease
Alzheimer's DiseaseUnlock trial analytics
PHASE2COMPLETED
SB-742457 And Donepezil In Alzheimer's Disease
Alzheimer's DiseaseUnlock trial analytics
PHASE2COMPLETED
A Dose Ranging Study To Investigate The Efficacy And Safety Of SB-742457 In Alzheimer's Disease
Alzheimer's DiseaseUnlock trial analytics

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 to 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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Frequently asked questions about SB-742457

What is SB-742457 used for?

SB-742457 is an investigational small molecule being developed for the treatment of Alzheimer's disease. It has been studied in patients with mild-to-moderate Alzheimer's disease, both as a monotherapy and in combination with donepezil. The drug is not approved and remains in clinical development.

Who makes SB-742457?

SB-742457 is being developed by GSK plc, a global pharmaceutical company listed on the London Stock Exchange under the ticker GSK. GSK has sponsored multiple clinical trials of SB-742457 in Alzheimer's disease, including Phase 1 and Phase 2 studies.

What phase is SB-742457 in?

SB-742457 is in Phase 2 clinical development for Alzheimer's disease. All five completed trials were Phase 1 or Phase 2 studies. The drug is investigational and has not been approved by regulatory authorities. No Phase 3 trials have been initiated.

What clinical trials is SB-742457 in?

SB-742457 has been studied in five completed trials, including NCT00224497, a dose-ranging Phase 2 study in Alzheimer's disease with 380 participants, and NCT00708552, a Phase 2 study comparing SB-742457 or donepezil versus placebo in 576 patients with mild-to-moderate Alzheimer's disease.

Is SB-742457 the same as donepezil?

No, SB-742457 is not the same as donepezil. Donepezil is an approved acetylcholinesterase inhibitor used to treat Alzheimer's disease symptoms. SB-742457 is a separate investigational compound. In one trial, NCT00708552, SB-742457 was compared directly against donepezil and placebo.