Familial Hypercholesterolemia, Hypercholesterolemia
Conditions
Brief summary
The goal of this study is to evaluate the efficacy, safety, and tolerability of enlicitide decanoate in adult participants with hypercholesterolemia. The primary hypothesis is that enlicitide decanoate is superior to placebo on mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 24.
Interventions
Oral tablet
DRUGPlacebo
Oral tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a history of a major atherosclerotic cardiovascular disease (ASCVD) event and LDL-C ≥55 mg/dL OR, if no history of a major ASCVD event, has intermediate to high risk for development of a first major ASCVD event and LDL-C ≥70 mg/dL. * Is treated with a moderate- or high-intensity statin OR is treated with low-intensity statin with documentation of intolerance to a moderate or high-intensity statin OR is not receiving statins with documentation of statin intolerance * If on any lipid-lowering therapies (LLTs), should be on a stable dose with no planned medication change.
Exclusion criteria
* Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous FH, or double heterozygous FH * Has a history of heart failure or heart failure hospitalization within 3 months before first study visit * Is undergoing or previously underwent an LDL-C apheresis program within 3 months before first study visit or plans to initiate an LDL-C apheresis program * Was previously treated/is being treated with certain other cholesterol lowering medications, including protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors without adequate washout
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 24 | Baseline and Week 24 | Blood samples collected at baseline and Week 24 were used to assess mean percent change in LDL-C. |
| Number of Participants With One or More Adverse Events (AEs) | Up to 60 weeks | 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 Discontinued Study Drug Due to an AE | Up to 52 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in LDL-C at Week 52 | Baseline and Week 52 | Blood samples collected at baseline and Week 52 were used to assess mean percent change in LDL-C. |
| Mean Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 | Baseline and Week 24 | Blood samples collected at baseline and Week 24 were used to assess mean percent change in non-HDL-C. |
| Mean Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24 | Baseline and Week 24 | Blood samples collected at baseline and Week 24 were used to assess mean percent change in ApoB. |
| Percent Change From Baseline in Lipoprotein(a) (Lp(a)) at Week 24 | Baseline and Week 24 | Blood samples collected at baseline and Week 24 were used to assess percent change in Lp(a). |
| Percentage of Participants With LDL-C <70 mg/dL and ≥50% Reduction From Baseline at Week 24 | Baseline and Week 24 | Blood samples collected at baseline and Week 24 were used to assess the percentage of participants who have LDL-C \<70 mg/dL and ≥50% reduction from baseline. Participants who did not have a Week 24 assessment are considered as not being at the LDL-C goal. |
| Percentage of Participants With LDL-C <55 mg/dL and ≥50% Reduction From Baseline at Week 24 | Baseline and Week 24 | Blood samples collected at baseline and Week 24 were used to assess the percentage of participants who have LDL-C \<55 mg/dL and ≥50% reduction from baseline. Participants who did not have a Week 24 assessment are considered as not being at the LDL-C goal. |
Countries
Argentina, China, Colombia, Germany, Israel, Italy, Japan, Mexico, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Participants ≥18 years old with a prior major atherosclerotic cardiovascular disease (ASCVD) event and low-density lipoprotein cholesterol (LDL-C) ≥55 mg/dL (≥1.42 mmol/L) or, if they had no prior ASCVD event, were at intermediate-to-high risk for a first major ASCVD event with LDL-C ≥70 mg/dL (≥1.81 mmol/L) were eligible to be enrolled in this study.
Pre-assignment details
A total of 2912 participants were originally enrolled in the study. 3 participants were simultaneously enrolled at more than one study site or in more than one enlicitide study. As pre-specified in the protocol for cases of simultaneous enrollment, these participants were excluded from all analyses, including disposition.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.7 Years STANDARD_DEVIATION 10.7 |
| Baseline Low-density Lipoprotein Cholesterol (LDL-C) | 95.0 mg/dL STANDARD_DEVIATION 38.8 |
| Baseline Statin Dose Intensity High intensity | 1039 Participants |
| Baseline Statin Dose Intensity Low intensity | 35 Participants |
| Baseline Statin Dose Intensity Moderate intensity | 384 Participants |
| Baseline Statin Dose Intensity No statin therapy | 65 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 545 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2091 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 253 Participants |
| Race (NIH/OMB) Black or African American | 252 Participants |
| Race (NIH/OMB) More than one race | 318 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1030 Participants |
| Sex: Female, Male Female | 367 Participants |
| Sex: Female, Male Male | 1165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 15 / 1,940 | 8 / 969 |
| other Total, other adverse events | 0 / 1,935 | 0 / 969 |
| serious Total, serious adverse events | 191 / 1,935 | 116 / 969 |
Outcome results
None listed