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 heterozygous familial 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 (placebo).
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 possible or definite diagnosis of heterozygous familial hypercholesterolemia (HeFH) based on a locally accepted diagnostic algorithm * Has an LDL-C ≥55 mg/dL or ≥70 mg/dL depending on medical history * Is treated with a moderate- or high-intensity statin medication * Is on a stable dose of all background lipid-lowering therapies (LLTs) 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
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 were collected at baseline and at Week 24 to determine mean percent change in LDL-C. The two treatment groups were compared using an analysis of covariance model with treatment as a fixed effect and baseline LDL-C as a covariate. |
| Number of Participants With Adverse Events (AEs) | Up to 64 weeks (8 weeks postdose) | An AE was defined as 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 56 weeks | An AE was defined as 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 were collected at baseline and at Week 52 to determine mean percent change in LDL-C. The two treatment groups were compared using an analysis of covariance model with treatment as a fixed effect and baseline LDL-C as a covariate. |
| Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24 | Baseline and Week 24 | Blood samples were collected at baseline and at Week 24 to determine mean percent change in non-HDL-C. The two treatment groups were compared using an analysis of covariance model with treatment as a fixed effect and baseline non-HDL-C as a covariate. |
| Mean Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24 | Baseline and Week 24 | Blood samples were collected at baseline and at Week 24 to determine mean percent change in ApoB. The two treatment groups were compared using an analysis of covariance model with treatment as a fixed effect and baseline ApoB as a covariate. |
| Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24 | Baseline and Week 24 | Blood samples were collected at baseline and at Week 24 to determine percent change in Lp(a). For percent change in Lp(a) at Week 24, the two treatment groups were analyzed using the Wilcoxon signed rank test with Hodges-Lehmann estimation. |
| Percentage of Participants With LDL-C <70 mg/dL and ≥50% Reduction From Baseline at Week 24 | Baseline and Week 24 | Blood samples were collected at baseline and at Week 24 to determine the percentage of participants who had LDL-C \<70 mg/dL and ≥50% reduction from baseline. The two treatment groups were analyzed based on the Miettinen and Nurminen method for the difference in percentage. |
| Percentage of Participants With LDL-C <55 mg/dL and ≥50% Reduction From Baseline at Week 24 | Baseline and Week 24 | Blood samples were collected at baseline and at Week 24 to determine the percentage of participants who had LDL-C \<55 mg/dL and ≥50% reduction from baseline. The two treatment groups were analyzed based on the Miettinen and Nurminen method for the difference in percentage. |
Countries
Australia, Brazil, Canada, Chile, Colombia, Czechia, Finland, Hong Kong, Hungary, Israel, Netherlands, New Zealand, Norway, Singapore, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 52.4 Years STANDARD_DEVIATION 13.5 |
| Baseline Low-density Lipoprotein Cholesterol (LDL-C) | 115.6 mg/dL STANDARD_DEVIATION 46.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 50 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 14 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 | 211 Participants |
| Sex: Female, Male Female | 155 Participants |
| Sex: Female, Male Male | 148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 202 | 0 / 101 |
| other Total, other adverse events | 102 / 202 | 43 / 101 |
| serious Total, serious adverse events | 9 / 202 | 4 / 101 |
Outcome results
None listed