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LY2409021

Phase 2

Diabetes Mellitus, Type 2 | Small molecule | Metabolic |Eli Lilly and Company|Last Updated: Mar 8, 2019

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials6
Total Enrollment529

FDA Designations

No designations recorded

Clinical trial landscape

LY2409021 · 12 trials · 7 indications

Phase 2 3Phase 1 9
NCT02091362A Study of LY2409021 on Blood Pressure and Pulse Rate in Participants With Type 2 Diabetes MellitusType 2 Diabetes Mellitus
COMPLETED270 Analytics
NCT01241448A Study of LY2409021 in Patients With Type 2 DiabetesDiabetes Mellitus, Type 2
COMPLETED263 Analytics
NCT00871572A Study for Participants With Type 2 Diabetes MellitusDiabetes Mellitus, Type 2
COMPLETED87 Analytics
PHASE2COMPLETED
A Study of LY2409021 on Blood Pressure and Pulse Rate in Participants With Type 2 Diabetes Mellitus
Type 2 Diabetes MellitusUnlock trial analytics
PHASE2COMPLETED
A Study of LY2409021 in Patients With Type 2 Diabetes
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE2COMPLETED
A Study for Participants With Type 2 Diabetes Mellitus
Diabetes Mellitus, Type 2Unlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline to 6 Weeks in Mean 24-Hour Systolic Blood Pressure
Baseline, 6 Weeks

Systolic blood pressure obtained from Ambulatory Blood Pressure Monitoring (ABPM).

Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c)
Baseline, 24 weeks

Least squares means of the change from baseline is from a mixed-model repeated measures analysis (MMRM). The model included terms for treatment group, baseline HbA1c, metformin use, visit, and visit-by-treatment interaction.

Mean Change in Glycosylated Hemoglobin A1c (HbA1c)
Baseline, Week 12

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was calculated using a mixed-model repeated measures analysis (MMRM) that included terms for treatment group, baseline HbA1c, metformin use, visit, and visit-by-treatment interaction.

Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2409021
Pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 192, 264, and 336 hours post-dose

Area under the concentration versus time curve from zero to infinity (AUC\[0-inf\]) of LY2409021 is presented.

Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021
Pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 192, 264, and 336 hours post-dose
Pharmacokinetics: Time to Maximum Observed Drug Concentration (Tmax) of LY2409021
Pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 192, 264, and 336 hours post-dose
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021
Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose
Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Infinity (AUC 0-∞) of LY2409021
Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose
Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021
Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)
Pharmacodynamics: Change From Baseline to Day 2 in 24-hour Insulin Dose
Baseline (Day 1), Day 2

The mean absolute change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported.

Change From Baseline to Day 28 in Liver Fat Average Percent (%)
Baseline, Day 28 (Pre-meal)

Measured by magnetic resonance (MR) scanning.

Change From Baseline to Day 28 in Hepatic Glycogen Content
Baseline, Day 28 (Pre-meal)

Measured by MR scanning.

Part B: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) Corrected QT Intervals (LY2409021)
Baseline, 2, 4, 6, 8, 12, and 24 hours

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Least Squares (LS) means were calculated using mixed effects model with fixed effects for treatment, time, period, sequence, and the time-by-treatment interaction, random effects for participant, the participant-by-treatment interaction, and participant-by-time interaction.

Number of participants with one or more drug related adverse events (AEs) or any serious AEs
From first dose of study drug up to discharge (at least 28 days after last dose)
Maximum glucose response during a 3-hour glucagon infusion
During a 3-hour glucagon infusion

Secondary Endpoints

Change From Baseline to 6 Weeks in Mean 24-Hour Diastolic Blood Pressure
Baseline, 6 Weeks
Change From Baseline to 6 Weeks in Mean 24-Hour, Daytime, and Nighttime Peripheral Pulse Rate
Baseline, 6 Weeks
Change From Baseline to 6 Weeks in Mean 24-Hour, Daytime, and Nighttime Pulse Pressures
Baseline, 6 Weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelCROSSOVER
PurposeBASIC_SCIENCE

Treatment Arms

ArmTypeDescription
PlaceboPLACEBO_COMPARATORSingle daily dose of placebo matching LY2409021 administered orally in 1 of 2 treatment periods.
LY2409021EXPERIMENTALSingle daily dose of 20 milligrams (mg) LY2409021 administered orally in 1 of 2 treatment periods.
2.5 mg LY2409021EXPERIMENTALTaken orally once daily for 24 weeks. Participants who entered the study on stable metformin therapy were to continue at the dose prescribed by their physician.
10 mg LY2409021EXPERIMENTALTaken orally once daily for 24 weeks. Participants who entered the study on stable metformin therapy were to continue at the dose prescribed by their physician.
20 mg LY2409021EXPERIMENTALTaken orally once daily for 24 weeks. Participants who entered the study on stable metformin therapy were to continue at the dose prescribed by their physician.
LY2409021 10 milligrams (mg)EXPERIMENTAL -
LY2409021 30 mgEXPERIMENTAL -
LY2409021 60 mgEXPERIMENTAL -
LY2409021 ControlEXPERIMENTALHealthy participants received a single 80 mg dose of LY2409021 orally on Day 1 of the study.
LY2409021 Mild Renal ImpairmentEXPERIMENTALParticipants received a single 80 mg dose of LY2409021 orally on Day 1 of the study.
LY2409021 Moderate Renal ImpairmentEXPERIMENTALParticipants received a single 80 mg dose of LY2409021 orally on Day 1 of the study.
LY2409021 Severe Renal ImpairmentEXPERIMENTALParticipants received a single 80 mg dose of LY2409021 orally on Day 1 of the study.
LY2409021 End Stage Renal DiseaseEXPERIMENTALParticipants received a single 80 mg dose of LY2409021 orally on Day 1 of Period 1 of the study and a single 80 mg dose of LY2409021 orally on Day 1 of Period 2 of the study.
LY2409021 Only (Part A, Cohort 1)EXPERIMENTALPart A, Period 1. Participants will receive a single 20-milligram (mg) oral dose of LY2409021 on Day 1.
LY2409021+Gemfibrozil (Part A, Cohort 1)EXPERIMENTALPart A, Period 2. Participants will receive a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants will also receive a single 20-mg oral dose of LY2409021 on Day 4.
LY2409021 Only (Part A, Cohort 2)EXPERIMENTALPart A, Period 1. Participants will receive a single 20-mg oral dose of LY2409021 on Day 1.
LY2409021+Ketoconazole (Part A, Cohort 2)EXPERIMENTALPart A, Period 2. Participants will receive a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
LY2409021+Clarithromycin (Part B)EXPERIMENTALPart B. Participants will receive a twice-daily 500-mg oral dose of clarithromycin on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
100 mg LY2409021EXPERIMENTALLY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2. Placebo: 2 capsules, administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.
300 mg LY2409021EXPERIMENTALLY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2. Glucagon: 1 mg administered via intramuscular injection on Day 3.
15 mg LY2409021EXPERIMENTALPart B - 1 capsule of 15 mg LY2409021 orally once a day for 28 days. (Arm added in September, 2012, per protocol amendment.)
60 mg LY2409021EXPERIMENTALPart A - 4 capsules of 15 mg LY2409021 administered orally once a day for 28 days.
Part A: LY2409021EXPERIMENTALParticipants will receive 2 standard meals; one alone without LY2409021, and one along with a single dose of 300 milligrams (mg) LY2409021 administered orally. Participants enrolled in Part A will not be allowed to participate in Part B.
Part B: LY2409021EXPERIMENTAL300 milligrams (mg) LY2409021 administered orally as a single dose on Day 1 of the relevant treatment period. The treatment and washout period was a total of 15 days in length.
Part B: PlaceboPLACEBO_COMPARATORAdministered orally as a single dose on Day 1 of the relevant treatment period. The treatment and washout period was a total of 15 days in length.
Part B: MoxifloxacinACTIVE_COMPARATOR400 milligrams (mg) Moxifloxacin administered orally as a single dose on Day 1 of the relevant treatment period. The treatment and washout period was a total of 15 days in length.
5 mg LY2409021EXPERIMENTAL5 mg LY2409021 administered orally once daily for 4 weeks
30 mg LY2409021EXPERIMENTAL30 mg LY2409021 administered orally once daily for 4 weeks
90 mg LY2409021EXPERIMENTAL90 mg LY2409021 administered orally once daily for 4 weeks
22.5 mg LY2409021EXPERIMENTAL22.5 mg LY2409021 administered once, orally
200 mg LY2409021EXPERIMENTAL200 mg LY2409021 administered once, orally
500 mg LY2409021EXPERIMENTAL500 mg LY2409021 administered once, orally
Healthy-PlaceboPLACEBO_COMPARATORPlacebo (capsule) administered once, orally
Healthy-2.5 mg LY2409021EXPERIMENTAL2.5 mg LY2409021 administered once, orally
Healthy-10 mg LY2409021EXPERIMENTAL10 mg LY2409021 administered once, orally
Healthy-30 mg LY2409021EXPERIMENTAL30 mg LY2409021 administered once, orally
Healthy-100 mg LY2409021EXPERIMENTAL100 mg LY2409021 administered once, orally
Healthy-250 mg LY2409021EXPERIMENTAL250 mg LY2409021 administered once, orally
Healthy-500 mg LY2409021EXPERIMENTAL500 mg LY2409021 administered once, orally
Diabetic-PlaceboPLACEBO_COMPARATORPlacebo (capsule) administered once, orally
Diabetic-75 mg LY2409021EXPERIMENTAL75 mg LY2409021 administered once, orally
Diabetic-200 mg LY2409021EXPERIMENTAL200 mg LY2409021 administered once, orally
Diabetic-500 mg LY2409021EXPERIMENTAL500 mg LY2409021 administered once, orally

Interventions

NameTypeDescription
LY2409021DRUGAdministered orally
PlaceboDRUGAdministered orally
MetforminDRUGAdministered as background therapy.
GemfibrozilDRUG -
KetoconazoleDRUG -
ClarithromycinDRUG -
GlucagonDRUGAdministered via intramuscular injection
MoxifloxacinDRUGAdministered orally
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites30

Inclusion Criteria: * Have type 2 diabetes mellitus (according to the World Health Organization diagnostic criteria) and use diet and exercise alone or in combination with a stable dose of metformin ( \>/=1000 mg/day \[or \<1000 mg, if documented intolerance to 1000 mg or higher dosages\] immediate...

Countries:United StatesCzechiaMexicoPolandPuerto RicoGermanyItalyRomaniaSlovakiaSpainLithuaniaUnited KingdomSingapore
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Frequently asked questions about LY2409021

What is LY2409021 used for?

LY2409021 is an investigational small molecule being studied for metabolic conditions, including Type 2 Diabetes Mellitus, Type 1 Diabetes Mellitus, and chronic kidney failure. It has been evaluated in healthy volunteers and in participants with Type 2 diabetes across multiple Phase 1 clinical trials.

Who makes LY2409021?

LY2409021 is being developed by Eli Lilly and Company, a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol LLY. The drug is in Phase 1 clinical development for metabolic indications.

What phase is LY2409021 in?

LY2409021 is in Phase 1 clinical development. All six clinical trials listed for the drug have been completed, with no active trials currently ongoing. The drug remains investigational and has not been approved by regulatory authorities.

What clinical trials is LY2409021 in?

LY2409021 has completed six Phase 1 trials, including NCT01460368, a study on its effects on heart electrical impulses in 67 participants with Type 2 diabetes, and NCT01588366, a liver effects study in 30 participants. Other trials include NCT01606397 and NCT01929109.

Is LY2409021 the same as any other drug?

LY2409021 is the primary identifier for this investigational compound developed by Eli Lilly. No alternative names have been established for this drug in the available clinical trial data.