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Enlicitide

Phase 3

Hypercholesterolemia | Small molecule | Metabolic |Merck & Company, Inc.|Last Updated: Sep 1, 2026

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment301

FDA Designations

No designations recorded

Clinical trial landscape

Enlicitide · 11 trials · 6 indications

Phase 3 2Phase 1 9
NCT07216482A Clinical Study of Enlicitide in Participants With High Cholesterol (MK-0616-037)Hyperlipidemia
ACTIVE NOT_RECRUITING996 Analytics
NCT06450366A Study to Evaluate the Efficacy and Safety of Enlicitide (MK-0616, Oral PCSK9 Inhibitor) Compared With Ezetimibe or Bempedoic Acid or Ezetimibe and Bempedoic Acid in Adults With Hypercholesterolemia (MK-0616-018/CORALreef AddOn)Hypercholesterolemia
COMPLETED301 Analytics
PHASE3ACTIVE NOT_RECRUITING
A Clinical Study of Enlicitide in Participants With High Cholesterol (MK-0616-037)
HyperlipidemiaUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Efficacy and Safety of Enlicitide (MK-0616, Oral PCSK9 Inhibitor) Compared With Ezetimibe or Bempedoic Acid or Ezetimibe and Bempedoic Acid in Adults With Hypercholesterolemia (MK-0616-018/CORALreef AddOn)
HypercholesterolemiaUnlock trial analytics

Study Endpoints

Primary Endpoints

Mean Percent Change from Baseline in LDL-C at Week 8 (Enlicitide + Rosuvastatin Versus Placebo)
Baseline and Week 8

Blood samples will be collected at baseline and at Week 8 to assess mean percent change in LDL-C between participants treated with enlicitide and rosuvastatin versus placebo.

Mean Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Day 56
Baseline and Day 56

Blood samples were collected at baseline and after 56 days of treatment to assess mean percentage change in LDL-C. The mean percent change from baseline in LDL-C at Day-56 is reported.

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Enlicitide in Plasma
Pre-dose and at designated timepoints (up to 168 hours post dose)

Blood samples will be collected to determine the AUC0-inf of enlicitide.

Maximum Observed Plasma Concentration (Cmax) of Enlicitide in Plasma
Pre-dose and at designated timepoints (up to 168 hours post dose)

Blood samples will be collected to determine the Cmax of enlicitide.

Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of enlicitide
At designated timepoints up to approximately 50 days

Blood samples will be collected to determine the AUC0-Last of enlicitide.

Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of enlicitide
At designated timepoints up to approximately 50 days

Blood samples will be collected to determine the AUC0-Inf of enlicitide.

Maximum Plasma Concentration (Cmax) of enlicitide
At designated timepoints up to approximately 50 days

Blood samples will be collected to estimate Cmax of enlicitide.

Part 1-Coffee: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of Enlicitide
Predose and at designated time points up to 168 hours

Blood samples will be collected to determine the AUC0-inf of enlicitide when administered with coffee

Part 1-Coffee: Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-last) of Enlicitide
Predose and at designated time points up to 168 hours

Blood samples will be collected to determine the AUC from time 0 to the time of last quantifiable sample of enlicitide when administered with coffee

Part 1 -Coffee : Maximum Plasma Concentration (Cmax) of Enlicitide
Predose and at designated time points up to 168 hours

Blood samples will be collected to determine the maximum observed drug concentration of enlicitide when administered with coffee

Part 2 -Tea: AUC0-last of Enlicitide
Predose and at designated time points up to 168 hours

Blood samples will be collected to determine the AUC from time 0 to the time of last quantifiable sample of enlicitide when administered with tea

Part 2 - Tea: AUC0-Inf of Enlicitide
Predose and at designated time points up to 168 hours

Blood samples will be collected to determine the AUC0-inf of enlicitide when administered with tea.

Part 2 -Tea: Cmax of Enlicitide
Predose and at designated time points up to 168 hours

Blood samples will be collected to determine the maximum observed drug concentration of enlicitide when administered with tea

Area Under the Concentration-Time Curve from Time 0 to 24 hours (AUC0-24hrs) of enlicitide in plasma
Pre-dose and at designated time points up to 24 hours post dose

Blood samples will be collected to determine the AUC0-24hr of enlicitide.

Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of enlicitide in plasma
Pre-dose and at designated time points up to 168 hours post dose

Blood samples will be collected to determine the AUC0-Last of enlicitide.

Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of enlicitide in plasma
Pre-dose and at designated time points up to 168 hours post dose

Blood samples will be collected to determine the AUC0-Inf of enlicitide.

Maximum Plasma Concentration (Cmax) of enlicitide in plasma
Pre-dose and at designated time points up to 168 hours post dose

Blood samples will be collected to determine the Cmax of enlicitide.

Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) for Lithium in Plasma
At designated timepoints (up to approximately 5 days post dose)

Blood samples will be collected to determine the AUC0-inf of lithium in plasma.

Area Under the Concentration versus Time Curve From Time Zero to Last Quantifiable Sample (AUC0-last) for Lithium in Plasma
At designated timepoints (up to approximately 5 days post dose)

Blood samples will be collected to determine the AUC0-last of lithium in plasma.

Cmax (Maximum Concentration) for Lithium in Plasma
At designated timepoints (up to approximately 5 days post dose)

Blood samples will be collected determine the Cmax of lithium in plasma.

Area Under the Concentration versus Time Curve from Time 0 to 24 hours (AUC0-24) of enlicitide in plasma
Pre-dose and at designated time points up to 24 hours post dose on Day 28

AUC0-24 of enlicitide in plasma will be determined.

Time to maximum plasma concentration (Tmax) of enlicitide in plasma
Pre-dose and at designated time points up to 24 hours post dose on Day 28

Tmax of enlicitide in plasma will be determined.

Apparent Clearance (CL/F) of enlicitide in plasma
Pre-dose and at designated time points up to 24 hours post dose on Day 28

CL/F of enlicitide in plasma will be determined.

Apparent volume of distribution during terminal phase (Vz/F) of enlicitide in plasma
Pre-dose and at designated time points up to 24 hours post dose on Day 28

Vz/F of enlicitide in plasma will be determined.

Number of participants who experience one or more adverse events (AEs)
Up to approximately 42 days

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Number of participants who discontinue study intervention due to an AE
Up to approximately 28 days

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Area Under the Concentration versus Time Curve from 0 to Infinity (AUC0-inf) of enlicitide in plasma
Pre-dose and at designated time points up to 168 hours post dose

AUC0-inf of enlicitide in plasma will be determined.

Area under the concentration versus time curve from time 0 to last quantifiable sample (AUC0-last) of enlicitide in plasma
Pre-dose and at designated time points up to 168 hours post dose

AUC0-last of enlicitide in plasma will be determined.

Apparent terminal half-life (t1/2) of enlicitide in plasma
Pre-dose and at designated time points up to 168 hours post dose

t1/2 of enlicitide in plasma will be determined.

Lag Time (tlag) of enlicitide in plasma
Pre-dose and at designated time points up to 168 hours post dose

tlag is the time from dosing to the first appearance in plasma. The tlag of enlicitide in plasma will be determined.

Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Digoxin in Plasma
At designated timepoints (up to 5 days)

AUC0-inf is the area under the plasma concentration versus time curve (AUC) for digoxin, from time zero (pre-dose) to extrapolated infinite time.

Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC0-inf) of Enlicitide
Predose and 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, and 168 hours postdose

Blood samples were collected at pre-specified time points to determine the AUC0-inf of enlicitide in plasma. AUC0-inf was defined as AUC0-last + (Cest,last/λz) where Cest, last was the estimated last measurable concentration, and λz was the apparent first-order terminal elimination rate constant.

Maximum Concentration (Cmax) of Enlicitide
Predose and 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, and 168 hours postdose

Blood samples were collected at pre-specified time points to determine the Cmax of enlicitide in participant's plasma. Cmax was defined as the maximum observed concentration of enlicitide in plasma after the administration of a given dose.

Secondary Endpoints

Mean Percent Change from Baseline in LDL-C at Week 8
Baseline and Week 8
Mean Percent Change from Baseline in Apolipoprotein B (ApoB) at Week 8
Baseline and Week 8
Number of Participants with One or More Adverse Events (AEs)
Up to approximately 20 weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelFACTORIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
EnlicitideEXPERIMENTALParticipants will receive enlicitide and a rosuvastatin-matching placebo. Both will be delivered orally once daily (QD) for up to 12 weeks.
Enlicitide + RosuvastatinEXPERIMENTALParticipants will receive enlicitide and rosuvastatin. Both will be delivered orally QD for up to 12 weeks.
RosuvastatinACTIVE_COMPARATORParticipants will receive rosuvastatin and an enlicitide-matching placebo. Both will be delivered orally QD for up to 12 weeks.
PlaceboPLACEBO_COMPARATORParticipants will receive an enlicitide-matching placebo and a rosuvastatin-matching placebo. Placebos will be delivered orally QD for up to 12 weeks.
EzetimibeACTIVE_COMPARATORParticipants receive ezetimibe 10mg, enlicitide-matching placebo, and bempedoic acid-matching placebo QD orally up to approximately 56 days.
Bempedoic AcidACTIVE_COMPARATORParticipants receive bempedoic acid 180mg, ezetimibe-matching placebo, and enlicitide-matching placebo QD orally up to approximately 56 days.
Ezetimibe + Bempedoic AcidACTIVE_COMPARATORParticipants receive ezetimibe 10 mg, bempedoic acid 180mg, enlicitide-matching placebo orally QD for approximately 56 days.
Treatment A: Enlicitide ReferenceEXPERIMENTALParticipants will receive a single oral dose of enlicitide reference formulation.
Treatment B: Enlicitide Formulation Test 1 - FedEXPERIMENTALParticipants will receive a single oral dose of enlicitide formulation test 1 after a high-fat breakfast.
Treatment C: Enlicitide Formulation Test 1 - FastedEXPERIMENTALParticipants will receive a single oral dose of enlicitide formulation test 1 under fasted conditions.
Treatment D: Enlicitide Formulation Test 2 - FedEXPERIMENTALParticipants will receive a single oral dose of enlicitide formulation test 2 after a high-fat breakfast.
Treatment E: Enlicitide Formulation Test 2 - FastedEXPERIMENTALParticipant will receive a single oral dose of enlicitide formulation test 2 under fasted conditions.
Dose regimen AEXPERIMENTALParticipants receive enlicitide orally at dose regimen A.
Dose regimen BEXPERIMENTALParticipants receive enlicitide orally at dose regimen B.
Dose regimen CACTIVE_COMPARATORParticipants receive enlicitide orally at dose regimen C.
Enlicitide Coffee Sequence 1EXPERIMENTALParticipants will be randomized to receive enlicitide administered with water in period 1 and enlicitide with coffee in period 2.
Enlicitide Coffee Sequence 2EXPERIMENTALParticipants will be randomized to receive enlicitide administered with coffee in period 1 and enlicitide with water in period 2.
Enlicitide Tea Sequence 1EXPERIMENTALParticipants will be randomized to receive enlicitide administered with water in period 1 and enlicitide with tea in period 2.
Enlicitide Tea Sequence 2EXPERIMENTALParticipants will be randomized to receive enlicitide administered with tea in period 1 and enlicitide with water in period 2.
Treatment A: enlicitide reference tabletEXPERIMENTALParticipants receive a single oral dose of enlicitide reference tablet.
Treatment B: enlicitide test tabletEXPERIMENTALParticipants receive a single oral dose of enlicitide test tablet.
Lithium CarbonateEXPERIMENTALOn Day 1 of Period 1, a single oral dose of lithium carbonate will be administered.
Enlicitide with Lithium CarbonateEXPERIMENTALOn Day 1 of Period 2, a single oral dose of lithium carbonate will be coadministered with a single oral dose of enlicitide.
Panel A: Severe Renal ImpairmentEXPERIMENTALParticipants with severe renal impairment receive enlicitide once daily (QD) for 28 days.
Panel B: HealthyEXPERIMENTALHealthy participants receive enlicitide QD for 28 days.
Enlicitide Treatment AEXPERIMENTALParticipants receive single oral dose of enlicitide after 8-hour overnight fast.
Enlicitide Treatment BEXPERIMENTALParticipants receive single oral dose of enlicitide 4 hours after morning meal.
Enlicitide Treatment CEXPERIMENTALParticipants receive single oral dose of enlicitide 3 hours after morning meal.
Enlicitide Treatment DEXPERIMENTALParticipants receive single oral dose of enlicitide 2 hours after morning meal.
Sequence 1: 0.25mg Digoxin-->0.25mg Digoxin plus 20mg enlicitide/180mg Sodium CaprateEXPERIMENTALParticipants will receive 1 tablet of 0.25mg Digoxin on Day 1 of period 1 and 1 tablet of 0.25mg Digoxin coadministered with 1 tablet of 20 mg enlicitide/180 mg sodium caprate on Day 1 of Period 2.
Sequence 2: 0.25mg Digoxin plus 20mg enlicitide/180mg Sodium Caprate-->0.25mg DigoxinEXPERIMENTALParticipants will receive 1 tablet of 0.25mg Digoxin coadministered with 1 tablet of 20 mg enlicitide/180 mg sodium caprate on Day 1 of Period 1 and will receive 1 tablet of 0.25mg Digoxin on Day 1 of period 2.
Moderate Hepatic Impairment (HI)EXPERIMENTALParticipants will receive a single oral dose of enlicitide on Day 1
Healthy ControlsEXPERIMENTALParticipants will receive a single oral dose of enlicitide on Day 1
Mild HIEXPERIMENTALParticipants will receive a single oral dose of enlicitide on Day 1

Interventions

NameTypeDescription
EnlicitideDRUGOral Tablet
RosuvastatinDRUGOral Capsule
Placebo for EnlicitideDRUGOral Tablet
Placebo for RosuvastatinDRUGOral Capsule
EzetimibeDRUGOral tablet
Bempedoic AcidDRUGOral capsule
Placebo for EzetimibeOTHERezetimibe-matching placebo oral tablet
Placebo for Bempedoic AcidOTHERbempedoic acid-matching placebo oral capsule
lithium carbonateDRUGOral capsule
DigoxinDRUGParticipants will receive 0.25 mg digoxin orally on Day 1 Period 1 in Arm A and Day 1 Period 2 in Arm B. They also receive Digoxin orally on Day 1, Period 2 in Arm A and on Day 1 Period 1 in Arm B coadministered with oral 20 mg enlicitide/180 mg sodium caprate.
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Eligibility Criteria

Age Range18 Years to 64 Years
SexALL
Healthy VolunteersNo
Study Sites87

Inclusion Criteria: -Has either not received lipid-lowering therapy (LLT) or has not received certain LLTs within a specified time period prior to the study. Exclusion Criteria: * Has a history of homozygous familial hypercholesterolemia (FH), compound heterozygous FH, or double heterozygous FH. ...

Countries:United StatesArgentinaAustraliaBrazilCanadaHungaryIsraelNew ZealandSpainTurkey (Türkiye)United KingdomFranceTaiwan
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Recent Changes (Last 90 Days)

LOWSep 1, 2026NCT07216482Enrollment: 975 → 996
LOWSep 1, 2026NCT07216482Enrollment: 975 → 996
LOWAug 26, 2026NCT07776665Status: NOT_YET_RECRUITING → RECRUITING
LOWAug 26, 2026NCT07776665Status: NOT_YET_RECRUITING → RECRUITING
LOWAug 25, 2026NCT07776665lastUpdatePostDate: changed
LOWAug 25, 2026NCT07776665lastUpdatePostDate: changed
LOWAug 20, 2026NCT07776665NEW_TRIAL: changed
LOWAug 20, 2026NCT07776665NEW_TRIAL: changed
LOWAug 5, 2026NCT07216482primaryCompletionDate: changed
MEDIUMJul 3, 2026NCT07481708TRIAL_REMOVED: changed
MEDIUMJul 3, 2026NCT07481708TRIAL_REMOVED: changed
MEDIUMJul 3, 2026NCT07481708TRIAL_REMOVED: changed
MEDIUMJun 29, 2026NCT06575959TRIAL_REMOVED: changed
MEDIUMJun 29, 2026NCT06575959TRIAL_REMOVED: changed
MEDIUMJun 29, 2026NCT06575959TRIAL_REMOVED: changed
MEDIUMJun 25, 2026NCT07216482Status: RECRUITING → ACTIVE_NOT_RECRUITING
MEDIUMJun 25, 2026NCT07216482Status: RECRUITING → ACTIVE_NOT_RECRUITING
MEDIUMJun 25, 2026NCT07216482Status: RECRUITING → ACTIVE_NOT_RECRUITING
LOWJun 22, 2026NCT07216482lastUpdatePostDate: changed
LOWJun 22, 2026NCT07216482lastUpdatePostDate: changed

Frequently asked questions about Enlicitide

What is Enlicitide used for?

Enlicitide is an investigational small molecule being studied for hepatic insufficiency, hyperlipidemia, and hypercholesterolemia. It is also used in healthy volunteer studies to assess drug interactions, food effects, and formulations. Enlicitide is in Phase 1 clinical development and is not yet approved by the FDA.

Who makes Enlicitide?

Enlicitide is being developed by Merck & Company, Inc., which trades under the ticker MRK. Merck is conducting Phase 1 clinical trials to evaluate the drug's safety, tolerability, and pharmacokinetics in healthy participants and in people with hepatic insufficiency.

What phase is Enlicitide in?

Enlicitide is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. Merck has completed seven Phase 1 trials and has one active trial ongoing, with a total of 975 participants enrolled across all studies.

What clinical trials is Enlicitide in?

Enlicitide has been studied in several Phase 1 trials, including NCT06597760 (digoxin interaction), NCT06609512 (food effect), NCT06880874 (formulation evaluation), and NCT07481708 (formulation study). These trials enrolled healthy adults in the United States and assessed how the body processes the drug.

What does Enlicitide target?

Enlicitide is a small molecule with a peptide-like structure, classified under the -tide (peptide) target class. It is being investigated for its effects on lipid metabolism in conditions such as hyperlipidemia and hypercholesterolemia, though its specific molecular target is not disclosed in the available data.

Is Enlicitide the same as MK-0616?

Yes, Enlicitide is also known as MK-0616. Clinical trial records reference both names, such as in NCT06880874, which is titled 'A Clinical Study to Evaluate Enlicitide (MK-0616) Formulations in Healthy Adult Participants.' Both names refer to the same investigational drug.