Hepatic Impairment, Hepatic Insufficiency
Conditions
Brief summary
Researchers have designed a new study medicine called enlicitide decanoate as a new way to lower the amount of low-density lipoprotein cholesterol (LDL-C) in a person's blood. Enlicitide decanoate will be called "enlicitide" from this point forward, The purpose of this study is to learn what happens to enlicitide in a person's body over time (a pharmacokinetic or PK study). Researchers will compare what happens to enlicitide in the body when it is given to people with hepatic impairment (HI- meaning the liver does not work properly) and people who are in good health. This study will have 2 parts. In Part 1, enlicitide will be given to people with moderate HI and people who are in good health. After Part 1, researchers may decide to include people who have mild HI and compare what happens to enlicitide in the body with people who are in good health.
Interventions
DRUGEnlicitide
Oral tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
The main inclusion criteria include but are not limited to the following: All participants: * Has been a non-smoker or moderate smoker (≤ 10 cigarettes per day or equivalent) for at least 3 months prior to starting the study * Has body mass index (BMI) ≥ 18.0 and ≤ 40.0 kg/m2 Participants with moderate or mild HI: * Diagnosis of chronic (\> 6 months) and stable (no sudden or severe episodes of illness due to worsening liver function in the past 2 months) hepatic insufficiency, and features cirrhosis (liver scarring) due to any cause. * Is generally in good health with the exception of HI. Healthy Control Participants: * Medically healthy with no clinically significant medical history, physical examination, or clinical laboratory profiles
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of Enlicitide | Predose and 0.5, 1, 1.5, 2, 3, 5, 8, 12, and 24 hours postdose | Blood samples were collected at pre-specified time points to determine the AUC0-24 of encilitide. AUC0-24 of encilitide was defined as the area under the concentration-time curve from time 0 to the 24 hours after the dosing of encilitide. |
| Area Under the Concentration Versus Time Curve From Time 0 to Last (AUC0-last) of Enlicitide in Plasma | 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-last of enlicitide in participant's plasma. AUC0 to last of enlicitide was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable (above lower limit of quantitation) concentration. AUC0-last was calculated using noncompartmental analysis. |
| Time to Maximum (Tmax) Observed Plasma Drug Concentration 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 tmax of enlicitide in participant's plasma. Tmax was defined as time to the maximum concentration of enlicitide reached. |
| Apparent Terminal Half-life (t1/2) 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 timepoints to determine the t1/2 of enlicitide. t1/2 was defined as the time required to divide the enlicitide plasma concentration by two after reaching pseudo-equilibrium, following a single dose of enlicitide. |
| Apparent Clearance (CL/F) 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 timepoints to determine the CL/F of enlicitide. CL/F was the apparent total clearance of enlicitide in plasma over time, assessed as the rate at which enlicitide was removed from the plasma. |
| Apparent Volume of Distribution During Terminal Phase (Vz/F) 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 timepoints to determine the Vz/F of enlicitide. Vz/F was the apparent volume of distribution of enlicitide between the plasma and the rest of the body, after dose, assessed as the total volume of enlicitide that would need to be uniformly distributed to achieve the desired plasma drug concentration. |
| Number of Participants Who Experienced a Treatment Emergent Adverse Event (TEAE) | Up to approximately 6 weeks | An adverse event (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. An AE was considered treatment-emergent if the onset date and time is at the time of or after the first study drug administration. The number of participants who experienced a TEAE were reported. |
| Number of Participants Who Experienced An Adverse Event (AE) | Up to approximately 6 weeks | 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 can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Number of participants who experienced an AE were reported. |
| Number of Participants Who Discontinued Study Due to an AE | Up to approximately 6 weeks | 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 can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Number of participants who discontinued from the study due to an AE were reported.. |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Participants with chronic, stable hepatic insufficiency (HI) meeting a Child-Pugh score of 7 - 9 corresponding to moderate HI were enrolled.
Pre-assignment details
Optional Part 2 in mild HI was not conducted; no mild hepatic impairment participants were enrolled.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.3 Years STANDARD_DEVIATION 5.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 19 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
None listed