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LY450139

Phase 3

Alzheimer's Disease | Small molecule | Neurology |Eli Lilly and Company|Last Updated: Mar 17, 2015

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials3
Total Enrollment2,693

FDA Designations

No designations recorded

Clinical trial landscape

LY450139 · 4 trials · 2 indications

Phase 3 2Phase 2 1Phase 1 1
NCT00762411Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With PlaceboAlzheimer's Disease
COMPLETED1,111 Analytics
NCT00594568Effect of LY450139 on the Long Term Progression of Alzheimer's DiseaseAlzheimer's Disease
COMPLETED1,537 Analytics
PHASE3COMPLETED
Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo
Alzheimer's DiseaseUnlock trial analytics
PHASE3COMPLETED
Effect of LY450139 on the Long Term Progression of Alzheimer's Disease
Alzheimer's DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 76 Weeks
Baseline (randomization), 76 weeks

The cognitive subscale of the ADAS (ADAS Cog11) was used as a primary efficacy measure and consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.

Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 16 Weeks After Cessation of Study Drug
Baseline (randomization), 16 weeks following treatment cessation

The cognitive subscale of ADAS (ADAS Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 76 Weeks
Baseline (randomization), 76 weeks

The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 16 Weeks After Cessation of Study Drug
Baseline (randomization), 16 weeks following treatment cessation

The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score at 76 Weeks
Baseline (randomization), 76 weeks

ADAS-Cog11 was used as a primary efficacy measure. It consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score at 16 Weeks After Cessation of Study Drug
Baseline (randomization), 16 weeks following treatment cessation

ADAS-Cog11 consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory Score at 76 Weeks
Baseline (randomization), 76 weeks

ADCS-ADL is a 23-item inventory developed as a Rater-administered questionnaire answered by the participant's caregiver. It measures performance of basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory Score at 16 Weeks After Cessation of Study Drug
Baseline (randomization), 16 weeks following treatment cessation

ADCS-ADL is a 23-item inventory developed as a Rater-administered questionnaire answered by the participant's caregiver. It measures performance of basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.

Safety and tolerability
To test hypothesis that LY450139, a gamma-secretase inhibitor, will reduce the rate of synthesis of 13C6-leucine-labeled Aβ (newly synthesized) in lumbar cerebrospinal fluid (CSF).
0-36 hours post dose

Secondary Endpoints

Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 76 Weeks
Baseline (randomization), 76 weeks
Change From Baseline in Neuropsychiatric Inventory (NPI) at 76 Weeks
Baseline (randomization), 76 weeks
Change From Baseline in the Resource Utilization in Dementia-Lite (RUD-Lite) up to 76 Weeks
Baseline (randomization), up to 76 weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
LY450139EXPERIMENTALParticipants received 60 milligrams (mg) LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
PlaceboPLACEBO_COMPARATORParticipants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
100 mg LY450139EXPERIMENTALParticipants received 60 mg LY450139 orally once daily for 2 weeks, followed by 100 mg LY450139 orally once daily until Week 88.
140 mg LY450139EXPERIMENTALParticipants received 60 mg LY450139 orally once daily for 2 weeks, followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
1EXPERIMENTAL100 mg LY 450139 oral
2EXPERIMENTAL140 mg LY450139 oral
3EXPERIMENTAL280 mg LY450139 oral
4EXPERIMENTALPlacebo

Interventions

NameTypeDescription
LY450139DRUGAdministered orally once daily.
PlaceboDRUGAdministered orally once daily.
LY450139 dihydrateDRUG -
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Eligibility Criteria

Age Range55 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites91

Inclusion Criteria: * Meets criteria for mild to moderate Alzheimer's disease (AD) with Mini-Mental State Examination score of 16 through 26 at visit 1 * Modified Hachinski Ischemia Scale score of less than or equal to 4 * Geriatric Depression Scale score of less than or equal to 6 * A magnetic res...

Countries:United StatesBrazilBulgariaCanadaChinaFranceGermanyHungaryItalyJapanMexicoRomaniaRussiaSerbiaSouth KoreaTaiwanTurkey (Türkiye)UkraineArgentinaAustraliaBelgiumChileDenmarkFinlandIndiaIsraelPolandSouth AfricaSpainSwedenUnited Kingdom
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Frequently asked questions about LY450139

What is LY450139 used for in Alzheimer's disease?

LY450139 is an investigational small molecule being studied for the treatment of Alzheimer's disease. It has been evaluated in clinical trials for mild to moderate Alzheimer's disease and for long-term progression of the disease. The drug is still in clinical development and has not been approved by regulatory authorities.

Who makes LY450139?

LY450139 is being developed by Eli Lilly and Company, a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol LLY. The company has sponsored clinical trials of this investigational drug in patients with Alzheimer's disease.

What phase is LY450139 in?

LY450139 has been studied in Phase 1, Phase 2, and Phase 3 clinical trials. All trials listed are completed, with no active trials currently ongoing. The drug remains investigational and has not received regulatory approval for any indication.

What clinical trials is LY450139 in?

LY450139 has been studied in several completed trials, including NCT00244322 (Phase 2, mild to moderate Alzheimer's disease), NCT00594568 (Phase 3, long-term progression), NCT00762411 (Phase 3, progression compared with placebo), and NCT00765115 (Phase 1, healthy subjects). These trials enrolled a total of 2,693 participants.

Is LY450139 the same as semagacestat?

LY450139 is also known as semagacestat, a gamma-secretase inhibitor developed by Eli Lilly for Alzheimer's disease. The drug was investigated in multiple clinical trials but did not demonstrate benefit and was discontinued. It is not approved for use.