Hepatic Impairment, Non-alcoholic Steatohepatitis
Conditions
Brief summary
The purpose of this study was to evaluate the pharmacokinetics of efinopegdutide in participants with hepatic impairment compared to healthy participants, and to examine the safety and tolerability of efinopegdutide.
Interventions
DRUGEfinopegdutide
Subcutaneous injection administered at a dose of 7 mg
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 and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * A participant assigned female at birth is eligible to participate if not pregnant or breastfeeding, is not a participant of childbearing potential (POCBP), or is a POCBP and agrees to follow contraceptive guidance during the study intervention period and for at least 35 days after the last dose of study intervention. * For participants with moderate or severe hepatic impairment: Have a diagnosis of chronic (\>6 months), stable, hepatic impairment with features of cirrhosis due to any etiology (stability of hepatic disease should correspond to no acute episodes of illness within the previous 2 months due to deterioration in hepatic function).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Volume of Distribution (Vz/F) of Efinopegdutide | At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35 | Blood samples collected at multiple timepoints post-dose were used to determine the Vz/F. |
| Apparent Terminal Half-life (t/12) of Efinopegdutide | At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35 | Blood samples collected at multiple timepoints post-dose were used to determine the t1/2. |
| Apparent Total Clearance (CL/F) of Efinopegdutide | At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35 | Blood samples collected at multiple timepoints post-dose were used to determine the CL/F. |
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Efinopegdutide | At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35 | Blood samples collected at multiple timepoints post-dose were used to determine the AUC0-inf. |
| Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Efinopegdutide | At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35 | Blood samples collected at multiple timepoints post-dose were used to determine the AUC0-last. |
| Maximum Plasma Concentration (Cmax) of Efinopegdutide | At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35 | Blood samples collected at multiple timepoints post-dose were used to determine the Cmax. |
| Time to Maximum Concentration (Tmax) of Efinopegdutide | At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35 | Blood samples collected at multiple timepoints post-dose were used to determine the Tmax of efinopegdutide. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Discontinued Study Intervention Due to an AE | Up to 35 days | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to 35 days | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment Participants with moderate hepatic impairment received a single 7 mg dose of efinopegdutide 14 mg/ml by subcutaneous (SC) injection. | 8 |
| Efinopegdutide in Participants With Severe Hepatic Impairment Participants with severe hepatic impairment received a single 7 mg dose of efinopegdutide 14 mg/ml by SC injection. | 8 |
| Efinopegdutide in Healthy-Matched Control Group Healthy matched participants received a single 7 mg dose of efinopegdutide 14 mg/ml by SC injection. | 6 |
| Total | 22 |
Baseline characteristics
| Characteristic | Efinopegdutide in Participants With Moderate Hepatic Impairment | Efinopegdutide in Participants With Severe Hepatic Impairment | Efinopegdutide in Healthy-Matched Control Group | Total |
|---|---|---|---|---|
| Age, Continuous | 57.5 Years STANDARD_DEVIATION 9.5 | 48.5 Years STANDARD_DEVIATION 10.5 | 56.2 Years STANDARD_DEVIATION 7.1 | 53.9 Years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 7 Participants | 6 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants | 5 Participants | 21 Participants |
| Sex: Female, Male Female | 4 Participants | 0 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 3 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 6 |
| other Total, other adverse events | 2 / 8 | 4 / 8 | 4 / 6 |
| serious Total, serious adverse events | 1 / 8 | 0 / 8 | 0 / 6 |
Outcome results
Primary
Apparent Terminal Half-life (t/12) of Efinopegdutide
Blood samples collected at multiple timepoints post-dose were used to determine the t1/2.
Time frame: At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35
Population: All participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment | Apparent Terminal Half-life (t/12) of Efinopegdutide | 146 hour | Geometric Coefficient of Variation 13.5 |
| Efinopegdutide in Participants With Severe Hepatic Impairment | Apparent Terminal Half-life (t/12) of Efinopegdutide | 149 hour | Geometric Coefficient of Variation 26 |
| Efinopegdutide in Healthy-Matched Control Group | Apparent Terminal Half-life (t/12) of Efinopegdutide | 115 hour | Geometric Coefficient of Variation 32.3 |
Primary
Apparent Total Clearance (CL/F) of Efinopegdutide
Blood samples collected at multiple timepoints post-dose were used to determine the CL/F.
Time frame: At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35
Population: All participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment | Apparent Total Clearance (CL/F) of Efinopegdutide | 0.0491 L/hr | Geometric Coefficient of Variation 16.5 |
| Efinopegdutide in Participants With Severe Hepatic Impairment | Apparent Total Clearance (CL/F) of Efinopegdutide | 0.0460 L/hr | Geometric Coefficient of Variation 40.8 |
| Efinopegdutide in Healthy-Matched Control Group | Apparent Total Clearance (CL/F) of Efinopegdutide | 0.0478 L/hr | Geometric Coefficient of Variation 60 |
Primary
Apparent Volume of Distribution (Vz/F) of Efinopegdutide
Blood samples collected at multiple timepoints post-dose were used to determine the Vz/F.
Time frame: At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35
Population: All participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment | Apparent Volume of Distribution (Vz/F) of Efinopegdutide | 10.3 Liters | Geometric Coefficient of Variation 17.9 |
| Efinopegdutide in Participants With Severe Hepatic Impairment | Apparent Volume of Distribution (Vz/F) of Efinopegdutide | 9.88 Liters | Geometric Coefficient of Variation 57.8 |
| Efinopegdutide in Healthy-Matched Control Group | Apparent Volume of Distribution (Vz/F) of Efinopegdutide | 7.94 Liters | Geometric Coefficient of Variation 91.7 |
Primary
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Efinopegdutide
Blood samples collected at multiple timepoints post-dose were used to determine the AUC0-inf.
Time frame: At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35
Population: All participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Efinopegdutide | 143 hr*μg/mL |
| Efinopegdutide in Participants With Severe Hepatic Impairment | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Efinopegdutide | 152 hr*μg/mL |
| Efinopegdutide in Healthy-Matched Control Group | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Efinopegdutide | 146 hr*μg/mL |
90% CI: [0.61, 1.54]
90% CI: [0.63, 1.71]
Primary
Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Efinopegdutide
Blood samples collected at multiple timepoints post-dose were used to determine the AUC0-last.
Time frame: At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35
Population: All participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment | Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Efinopegdutide | 133 hr*μg/mL |
| Efinopegdutide in Participants With Severe Hepatic Impairment | Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Efinopegdutide | 125 hr*μg/mL |
| Efinopegdutide in Healthy-Matched Control Group | Area Under the Curve From Time 0 to Last Sampling Time (AUC0-last) of Efinopegdutide | 134 hr*μg/mL |
90% CI: [0.6, 1.65]
90% CI: [0.53, 1.65]
Primary
Maximum Plasma Concentration (Cmax) of Efinopegdutide
Blood samples collected at multiple timepoints post-dose were used to determine the Cmax.
Time frame: At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35
Population: All participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment | Maximum Plasma Concentration (Cmax) of Efinopegdutide | 0.348 μg/mL |
| Efinopegdutide in Participants With Severe Hepatic Impairment | Maximum Plasma Concentration (Cmax) of Efinopegdutide | 0.404 μg/mL |
| Efinopegdutide in Healthy-Matched Control Group | Maximum Plasma Concentration (Cmax) of Efinopegdutide | 0.474 μg/mL |
90% CI: [0.44, 1.21]
90% CI: [0.47, 1.53]
Primary
Time to Maximum Concentration (Tmax) of Efinopegdutide
Blood samples collected at multiple timepoints post-dose were used to determine the Tmax of efinopegdutide.
Time frame: At pre-specified timepoints on Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 11, Day 14, Day 21, and Day 35
Population: All participants who complied with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment | Time to Maximum Concentration (Tmax) of Efinopegdutide | 120.00 hour |
| Efinopegdutide in Participants With Severe Hepatic Impairment | Time to Maximum Concentration (Tmax) of Efinopegdutide | 72.04 hour |
| Efinopegdutide in Healthy-Matched Control Group | Time to Maximum Concentration (Tmax) of Efinopegdutide | 83.78 hour |
Secondary
Number of Participants Who Discontinued Study Intervention Due to an AE
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality.
Time frame: Up to 35 days
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment | Number of Participants Who Discontinued Study Intervention Due to an AE | 0 Participants |
| Efinopegdutide in Participants With Severe Hepatic Impairment | Number of Participants Who Discontinued Study Intervention Due to an AE | 0 Participants |
| Efinopegdutide in Healthy-Matched Control Group | Number of Participants Who Discontinued Study Intervention Due to an AE | 0 Participants |
Secondary
Number of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality.
Time frame: Up to 35 days
Population: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efinopegdutide in Participants With Moderate Hepatic Impairment | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Efinopegdutide in Participants With Severe Hepatic Impairment | Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |
| Efinopegdutide in Healthy-Matched Control Group | Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |