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LY3372689

Phase 2

Alzheimer Disease | Small molecule | Neurology |Eli Lilly and Company|Last Updated: Jun 12, 2026

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment327

FDA Designations

No designations recorded

Clinical trial landscape

LY3372689 · 6 trials · 2 indications

Phase 2 1Phase 1 5
NCT05063539A Study of LY3372689 to Assess the Safety, Tolerability, and Efficacy in Participants With Alzheimer's DiseaseAlzheimer Disease
COMPLETED327 Analytics
PHASE2COMPLETED
A Study of LY3372689 to Assess the Safety, Tolerability, and Efficacy in Participants With Alzheimer's Disease
Alzheimer DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline to End Time Point in Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)
Baseline, Week 100

iADRS is a simple linear combination of scores from 13-item alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). It is used to assess whether LY3372689 slows down the cognitive and functional decline associated with early symptomatic Alzheimer's Disease, compared to placebo. The iADRS score ranges from 0 to 144 with lower scores indicating worse performance and higher score better performance. Change from baseline was calculated using Bayesian disease progression model (DPM) adjusted for age at baseline, AChEI/Memantine use at baseline, pooled investigator. Data presented are posterior mean with 95% credible interval.

Urinary Excretion of LY3372689 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
Predose up to Day 17 post dose
Fecal Excretion of LY3372689 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
Predose up to Day 17 post dose
Percent O-GlcNAcase (OGA) Enzyme Occupancy (EO)
Approximately 2 to 96 hours following the first dose

Percent OGA EO

Percent OGA EO
Approximately 2 to 96 hours following the last dose
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Observed by the Investigator During Study Drug Administration
Baseline through final follow-up at approximately Day 30

A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module

Secondary Endpoints

Change From Baseline to End Time Point in iADRS (Overall Population)
Baseline, Week 100
Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)
Baseline, Week 76
Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Overall Population)
Baseline, Week 76
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
0.75 Milligram (mg) LY3372689EXPERIMENTALDouble-blind treatment period: Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks. Post treatment follow up period: Participants who received 0.75 mg LY3372689 during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring. Post treatment observational extension period: Participants who received 0.75 mg LY3372689 during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring.
3 mg LY3372689EXPERIMENTALDouble-blind treatment period: Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks. Post treatment follow up period: Participants who received 3 mg LY3372689 during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring. Post treatment observational extension period: Participants who received 3 mg LY3372689 during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring.
PlaceboPLACEBO_COMPARATORDouble-blind treatment period: Participants received placebo administered orally once daily for up to 124 weeks. Post treatment follow up period: Participants who received placebo during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring. Post treatment observational extension period: Participants who received placebo during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring.
[¹⁴C]-LY3372689EXPERIMENTALSingle dose of \[¹⁴C\]-LY3372689 administered orally.
LY3372689 + [18F]LSN3316612EXPERIMENTALLY3372689 administered orally followed by \[18F\]LSN3316612 PET tracer administered intravenously (IV) approximately 24 hours later.
LY3372689EXPERIMENTALLY3372689 administered orally

Interventions

NameTypeDescription
LY3372689DRUGgiven orally
PlaceboDRUGgiven orally
[¹⁴C]-LY3372689DRUGAdministered orally.
[18F]LSN3316612DIAGNOSTIC_TESTAdministered intravenously (IV).
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Eligibility Criteria

Age Range60 Years to 85 Years
SexALL
Healthy VolunteersNo
Study Sites69

Inclusion Criteria: * Gradual and progressive change in memory function reported by participants or informants for ≥ 6 months * MMSE score of 22 to 30 (inclusive) at screening * CDR global score of 0.5 to 1.0 (inclusive), with a memory box score ≥0.5. * Meet 18F flortaucipir positron emission tomog...

Countries:United StatesAustraliaCanadaJapanPoland
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Recent Changes (Last 90 Days)

MEDIUMJul 13, 2026NCT05063539TRIAL_REMOVED: changed
MEDIUMJul 13, 2026NCT05063539TRIAL_REMOVED: changed
MEDIUMJul 13, 2026NCT05063539TRIAL_REMOVED: changed

Frequently asked questions about LY3372689

What is LY3372689 used for?

LY3372689 is an investigational small molecule being studied for Alzheimer's disease and in healthy participants. It is being developed by Eli Lilly and Company. The drug has completed Phase 2 testing in patients with Alzheimer's disease, and Phase 1 trials have been completed in healthy volunteers.

What does LY3372689 target?

LY3372689 is a small molecule developed by Eli Lilly and Company. The specific molecular target of LY3372689 has not been disclosed in the available information. The drug is being studied for its safety, tolerability, and efficacy in participants with Alzheimer's disease.

Who makes LY3372689?

LY3372689 is being developed by Eli Lilly and Company, which trades under the ticker symbol LLY. The company has completed Phase 1 and Phase 2 clinical trials for this investigational small molecule, which is being studied for Alzheimer's disease.

What phase is LY3372689 in?

LY3372689 is in Phase 2 clinical development for Alzheimer's disease. The Phase 2 trial has been completed, and all five clinical trials for the drug have been completed. LY3372689 is investigational and has not been approved by the FDA.

What clinical trials is LY3372689 in?

LY3372689 has been studied in five completed clinical trials. These include Phase 1 safety studies in healthy participants (NCT03819270, NCT04106206, NCT05749848) and a Phase 2 efficacy study in Alzheimer's disease patients (NCT05063539). The Phase 2 trial enrolled 327 participants across the United States, Australia, Canada, Japan, and Poland.

Is LY3372689 the same as any other drug?

LY3372689 is the primary name for this investigational drug developed by Eli Lilly and Company. No alternative names have been reported for this compound. The drug is being studied for Alzheimer's disease and has completed Phase 2 clinical trials.