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LY2484595

Phase 2

Dyslipidemia | Small molecule | Cardiovascular |Eli Lilly and Company|Last Updated: Apr 2, 2019

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment398

FDA Designations

No designations recorded

Clinical trial landscape

LY2484595 · 5 trials · 4 indications

Phase 2 2Phase 1 3
NCT01375075A Study of LY2484595 in Japanese SubjectsDyslipidemias
COMPLETED165 Analytics
NCT01105975A Study of LY2484595 in Patients With High LDL-C or Low HDL-CDyslipidemia
COMPLETED398 Analytics
PHASE2COMPLETED
A Study of LY2484595 in Japanese Subjects
DyslipidemiasUnlock trial analytics
PHASE2COMPLETED
A Study of LY2484595 in Patients With High LDL-C or Low HDL-C
DyslipidemiaUnlock trial analytics

Study Endpoints

Primary Endpoints

Percent Change From Baseline to 12 Weeks in High Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo
Baseline and Week 12

Percent change from baseline = 100\*(post-baseline assessment - baseline assessment)/baseline assessment. Higher values in the percent change from baseline represented an improvement for HDL-C and lower values in the percent change from baseline represented an improvement for LDL-C. Least Squares (LS) mean was adjusted for baseline value of the variable analyzed.

Percent Change From Baseline to 12 Weeks Endpoint in High Density Lipoprotein Cholesterol (HDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin Monotherapy
Baseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Percent Change From Baseline to 12 Weeks Endpoint in Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 in Combination With Atorvastatin and Atorvastatin Monotherapy
Baseline, Week 12

Least Squares (LS) Mean values were controlled for region, baseline measurement, treatment, visit, and treatment by visit interaction.

Change From Baseline to Day 10 in QT Interval Corrected for Heart Rate (QTc) for LY2484595 Versus Placebo
Predose of Day 1, Day 10

Data were collected using a 12-lead electrocardiogram (ECG). The QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle and corrected for heart rate. Population-corrected QT interval (QTcP) formula: QTcP = QT / RR\^ß, where ß is the population correction factor.

Part 1: Number of Participants With 1 or More Adverse Events (AEs) or Any Serious AEs
Part 1: Baseline through ≥14 days after last dose of study drug (≥Day 28)

The number of participants with 1 or more AEs is summarized cumulatively. In addition, the number of participants with any serious AEs is summarized cumulatively. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2484595
Part 2, Period 1, Day 1 through Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post Dose; Period 2, Day 5 through Day 15: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 Hours Post Dose

The geometric least squares (LS) means for the maximum observed plasma concentration (Cmax) of LY2484595 following administration of LY2484595 alone and with ketoconazole are reported. Least squares means were calculated from an analysis of variance (ANOVA) model with a fixed effect for treatment and a random effect for participant. The LS means for each treatment and the 90% confidence intervals (CI) for the difference in means were back transformed from the log scale to provide estimates of the geometric means and 90% CIs for the ratio of the geometric means (LY2484595 coadministered with ketoconazole and LY2484595 alone).

Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax) of LY2484595
Part 2, Period 1, Day 1 through Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post Dose; Period 2, Day 5 through Day 15: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 Hours Post Dose

The median times to maximum observed plasma concentration (Tmax) of LY2484595 following administration of LY2484595 alone and with ketoconazole are reported.

Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of LY2484595
Part 2, Period 1, Day 1 through Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post Dose; Period 2, Day 5 through Day 15: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 Hours Post Dose

The geometric least squares (LS) means of area under the concentration-time curve (AUC) from time zero extrapolated to infinity (AUC0-∞) of LY2484595 following administration of LY2484595 alone and with ketoconazole are reported. Least squares means were calculated from an analysis of variance (ANOVA) model with a fixed effect for treatment and a random effect for participant. The LS means for each treatment and the 90% confidence intervals (CI) for the difference in means were back transformed from the log scale to provide estimates of the geometric means and 90% CIs for the ratio of the geometric means (LY2484595 coadministered with ketoconazole and LY2484595 alone).

Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2484595
Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose

Area under the concentration-time curve from time zero to infinity is presented.

Pharmacokinetics: Peak Plasma Concentration (Cmax) of LY2484595
Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose

Secondary Endpoints

Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 in Combination With Atorvastatin
Baseline, Weeks 2, 4, and 8
Pharmacokinetics - Area Under the Curve (AUC) of LY2484595 and Atorvastatin
Weeks 2, 4, 8, 12 (predose and postdose), and Week 16
The Number and Severity of Episodes of Rashes at Any Time From Baseline Through Week 12
Baseline through Week 12
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
30 milligrams (mg) LY2484595EXPERIMENTALAdministered orally once daily for 12 weeks
100 mg LY2484595EXPERIMENTALAdministered orally once daily for 12 weeks
500 mg LY2484595EXPERIMENTALAdministered orally once daily for 12 weeks
PlaceboPLACEBO_COMPARATORAdministered orally once daily for 12 weeks
10 mg AtorvastatinACTIVE_COMPARATORAdministered orally once daily for 12 weeks
100 mg LY2484595 + 10 mg AtorvastatinEXPERIMENTALAdministered orally once daily for 12 weeks
30 milligram (mg) LY2484595 monotherapyEXPERIMENTAL -
100 mg LY2484595 monotherapyEXPERIMENTAL -
500 mg LY2484595 monotherapyEXPERIMENTAL -
20 mg Atorvastatin monotherapyACTIVE_COMPARATOR -
100 mg LY2484595 + 20 mg AtorvastatinEXPERIMENTAL -
40 mg Simvastatin monotherapyACTIVE_COMPARATOR -
100 mg LY2484595 + 40 mg SimvastatinEXPERIMENTAL -
10 mg Rosuvastatin monotherapyACTIVE_COMPARATOR -
100 mg LY2484595 + 10 mg RosuvastatinEXPERIMENTAL -
1200 milligrams (mg) LY2484595EXPERIMENTALAdministered orally once daily for 10 days during 1 of the 3 crossover periods, separated by at least a 14-day washout period.
400 mg MoxifloxacinACTIVE_COMPARATORPositive control, unblinded treatment administered orally once during 1 of 3 crossover periods, separated by at least a 14-day washout period.
Part 1 (Cohort A): 100 mg, 1800 mg LY2484595, PlaceboEXPERIMENTALPeriod 1: Participants will receive either 100 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14 of Period 1. Washout period lasting ≥14 days. Period 2: Participants will receive either 1800 mg LY2484595 tablets or placebo tablets QD by mouth on Days 1 through 14 of Period 2.
Part 1 (Cohort B): 300 mg LY2484595, PlaceboEXPERIMENTALParticipants will receive either 300 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14.
Part 1 (Cohort C): 600 mg LY2484595, PlaceboEXPERIMENTALParticipants will receive either 600 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14.
Part 1 (Cohort D): 1200 mg LY2484595, PlaceboEXPERIMENTALParticipants will receive either 1200 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14.
Part 2 (Cohort E): 100 mg LY2484595 ± 400 mg KetoconazoleEXPERIMENTALPeriod 1: Participants will receive 100 milligrams (mg) LY2484595 tablet by mouth on Day 1 of Period 1. Washout period lasting ≥14 days. Period 2: Participants will receive 400 mg ketoconazole tablets once daily (QD) by mouth on Days 1 through 14 of Period 2. Participants will receive 100 mg LY2484595 tablet by mouth on Day 5 of Period 2.
Cohort A: Fixed Sequence of Meal ConditionsEXPERIMENTALLY2484595 (evacetrapib): 200 milligrams (mg) of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with no food. There was a washout of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with low-fat breakfast. There was another washout period of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with high-fat breakfast.
Cohort B: Comparison of Randomized TreatmentsEXPERIMENTALLY2484595 (evacetrapib): 100 mg of LY2484595 administered orally as an RF tablet given with a low-fat breakfast. There was a washout period of at least 14 days before crossing over and receiving 100 mg of LY2484595 administered orally as a SDSD-PG tablet given with a low-fat breakfast. There was another washout of at least 14 days before crossing over and receiving 300 mg of LY2484595 as a SDSD-PG tablet given with a low-fat breakfast.

Interventions

NameTypeDescription
LY2484595DRUGAdministered orally
PlaceboDRUGAdministered orally
AtorvastatinDRUGAdministered orally
SimvastatinDRUGAdministered daily by mouth for 12 weeks
RosuvastatinDRUGAdministered daily by mouth for 12 weeks
Placebo for LY2484595DRUGAdministered daily by mouth for 12 weeks
Placebo for StatinsDRUGAdministered daily by mouth for 12 weeks
MoxifloxacinDRUGSingle dose administered orally.
KetoconazoleDRUGAdministered orally
LY2484595 Reference Formulation (RF)DRUGAdministered orally
LY2484595 spray-dried solid dispersion-propyl gallate (SDSD-PG)DRUGAdministered orally
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Eligibility Criteria

Age Range20 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites5

Inclusion Criteria: Have Low HDL-C or High LDL-C criteria as follows: Low HDL lipid criteria: * HDL-C \<45 milligrams per deciliter (mg/dL) (men) and \<50 mg/dL (women), and * LDL-C according to Japan Atherosclerosis Society (JAS) guidelines as follows: * LDL-C \<190 mg/dL (0-1 risk factors) ...

Countries:JapanUnited StatesDenmarkGermanyNetherlandsPolandUnited Kingdom
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Frequently asked questions about LY2484595

What is LY2484595 used for?

LY2484595 is an investigational small molecule being studied for dyslipidemia, a condition of abnormal lipid levels in the blood. It has also been evaluated in healthy volunteers and healthy participants to assess its safety and pharmacokinetics. The drug is in clinical development by Eli Lilly and Company for the cardiovascular therapeutic area.

Who makes LY2484595?

LY2484595 is being developed by Eli Lilly and Company, a pharmaceutical company traded on the New York Stock Exchange under the ticker LLY. The company has sponsored clinical trials of the drug in the United States and Japan.

What phase is LY2484595 in?

LY2484595 has completed Phase 1 and Phase 2 clinical trials. The most advanced study, NCT01375075, was a Phase 2 trial in Japanese subjects with dyslipidemias. All trials listed for LY2484595 are completed, and the drug remains investigational, not approved by regulatory authorities.

What clinical trials has LY2484595 been in?

LY2484595 has been studied in four completed clinical trials. NCT01375075 was a Phase 2 study in Japanese subjects with dyslipidemias. NCT01448824, NCT01450098, and NCT01537887 were Phase 1 studies in healthy participants or volunteers in the United States, including a trial on the drug's effect on heart electrical activity.

Is LY2484595 the same as any other drug?

No alternative names for LY2484595 have been disclosed in the clinical trial records. The drug is identified solely by its code name LY2484595 in the studies sponsored by Eli Lilly and Company.