Hypercholesterolemia
Conditions
Brief summary
The main purpose of this study is to assess whether enlicitide is superior to ezetimibe or bempedoic acid or ezetimibe + bempedoic acid in reducing low-density lipoprotein cholesterol (LDL-C) in participants with hypercholesterolemia, and to evaluate its safety and tolerability. The primary study hypotheses are enlicitide is superior to ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid on mean percent change from baseline in LDL-C at week 8.
Interventions
DRUGEnlicitide
Oral tablet
DRUGEzetimibe
Oral tablet
DRUGBempedoic Acid
Oral capsule
enlicitide-matching placebo oral tablet
ezetimibe-matching placebo oral tablet
bempedoic acid-matching placebo oral capsule
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 either a) history of a major atherosclerotic cardiovascular disease (ASCVD) event or b) if no history of a major ASCVD event, has intermediate to high risk for development of a first major ASCVD event * Has fasted lipid values (evaluated by the central laboratory) at Visit 1 (Screening) as follows: a) history of a major ASCVD event with LDL-C ≥55 mg/dL (≥1.42 mmol/L) OR b) No history of a major ASCVD event with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (≥1.81 mmol/L) * Is treated with a low, moderate, or high intensity statin (±non-statin lipid lowering therapy \[LLT\]) * Is on a stable dose of all background LLTs with no planned medication or dose changes during the study * Is an individual of any sex/gender, from 18 years of age inclusive, at the time of providing the informed consent
Exclusion criteria
* Has a history of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria, compound heterozygous familial hypercholesterolemia (HeFH), or double HeFH * Has New York Heart Association class IV heart failure, or last known left ventricular ejection fraction ≤25% by any imaging method, or had a heart failure hospitalization within 3 months before Visit 1 (Screening) * Participants with a history of tendon disorder or tendon rupture * Participants with a history of gout * Is undergoing or previously underwent an LDL-C apheresis program within 3 months before Visit 1 (Screening) or plans to initiate an LDL-C apheresis program * Was previously treated/is being treated with certain other cholesterol lowering medications, including ezetimibe, bempedoic acid, or 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 56 | Baseline and Day 56 | Blood samples were collected at baseline and on day 56 of treatment to assess mean percent change in ApoB. The mean percent change from baseline in ApoB at Day 56 is reported. |
| Mean Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Day 56 | Baseline and Day 56 | Blood samples were collected at baseline and on day 56 of treatment to assess mean percent change in non-HDL-C. The mean percent change from baseline in non-HDL-C at 56 days is reported. |
| Median Percent Change From Baseline in Lipoprotein(a) Levels (Lp[a]) | Baseline and Day 56 | Blood samples were collected at baseline and on day 56 of treatment to assess median percent change in Lp(a) levels. The median percent change from baseline at Day 56 is reported. |
| Percentage of Participants Who at Day 56 Have an LDL-C <70 mg/dL and ≥50% Reduction From Baseline | Baseline and Day 56 | Blood samples were collected at baseline and after 56 days of treatment to assess the percentage of participants who have an LDL-C \<70 mg/dL and ≥50% reduction from baseline at day 56. The percentage of participants who have LDL-C \<70 mg/dL and ≥50% reduction from baseline is reported. |
| Percentage of Participants Who at Day 56 Have an LDL-C <55 mg/dL and ≥50% Reduction From Baseline | Baseline and Day 56 | Blood samples were collected at baseline and after 56 days of treatment to assess the percentage of participants who have an LDL-C \<55 mg/dL and ≥50% reduction from baseline at day 56. The percentage of participants who have LDL-C \<55 mg/dL and ≥50% reduction from baseline is reported. |
| Percentage of Participants With ≥1 Adverse Event (AE) | Up to approximately 147 days | An AE was 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. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE is reported. |
| Percentage of Participants Discontinuing From Study Intervention Due to AE | Up to approximately 91 days | An AE was 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. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to an AE is reported. |
Countries
Argentina, Canada, France, Israel, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
301 participants were randomized in 2:1:1:2 ratio to receive enlicitide, ezetimibe, bempedoic acid, or ezetimibe + bempedoic acid.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.4 Years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mean low-density lipoprotein cholesterol (LDL-C) at Baseline | 93.2 mg/dL STANDARD_DEVIATION 27.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 80 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 198 Participants |
| Renal Function measured by estimated Glomerular Filtration Rate (eGFR) ≥35 to <45 | 5 Participants |
| Renal Function measured by estimated Glomerular Filtration Rate (eGFR) ≥45 to <60 | 7 Participants |
| Renal Function measured by estimated Glomerular Filtration Rate (eGFR) ≥60 | 273 Participants |
| Sex: Female, Male Female | 112 Participants |
| Sex: Female, Male Male | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 50 | 0 / 50 | 0 / 100 |
| other Total, other adverse events | 0 / 101 | 3 / 50 | 3 / 50 | 0 / 100 |
| serious Total, serious adverse events | 0 / 101 | 4 / 50 | 1 / 50 | 0 / 100 |
Outcome results
None listed