Hepatic Impairment
Conditions
Keywords
Hepatic Impairment, Liver Function, Hepatic Function
Brief summary
The primary objective is to assess the pharmacokinetics (PK) of apraglutide in subjects with hepatic impairment compared with matched control subjects with normal hepatic function following single subcutaneous (SC) dose administration.
Detailed description
A two stage design, open label, multi-center, non-randomized trial to evaluate the the safety and tolerability of a single subcutaneous dose of apraglutide in subjects with varying degrees of hepatic function. The hepatic function will estimated with the Child-Pugh classification. Part 1: 8 subjects with moderate hepatic impairment (Cohort 1) and 8 subjects with normal hepatic function (Cohort 2). Part 2: 8 subjects with mild hepatic impairment (Cohort 3) and 8 subjects with normal hepatic function (from Cohort 2 where possible and additional subject). Part 2 will be conducted only if the geometric mean ratio (GMR) of area under the curve extrapolated to infinity (AUCinf) or area under the curve from zero to the last measurable point (AUClast) for the moderate hepatic impairment group compared to the control group is ≥2.
Interventions
DRUGApraglutide
Single dose of apraglutide
Sponsors
VectivBio AG
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
All Participants: * Age between 18 and 75 years inclusive * Subjects who are willing and able to comply with the study procedures * Subjects able to understand and willing to sign the informed consent * Body mass index (BMI) of ≥18 to ≤35 kg/m2; and a total body weight of \>50 kg (110 lb). * Women of childbearing potential (WOCBP) on highly effective method of contraception during the trial and for 1 month after the end of trial (EOT) visit. Sterilized or infertile or postmenopausal females. * Male subjects with a female partner of childbearing potential: highly effective methods of contraception and no sperm donation during the trial and for 1 month after (EOT) visit. Participants with impaired hepatic function: * Confirmed and documented diagnosis of cirrhosis * Moderate liver disease (Child-Pugh B): clinically stable for at least 1 month prior to screening * Mild liver disease (Child-Pugh A): clinically stable for at least 1 month prior to screening
Exclusion criteria
* History of clinically significant GI, bronchopulmonary, neurological, cardiovascular, endocrine, or allergic disease * Known hypersensitivity to the investigational medicinal product (IMP), any of their excipients or drugs of the same class * If capable of reproduction, unwilling to use an effective form of contraception * If a female of child-bearing potential, a positive urine/blood pregnancy test * Breast-feeding women * Positive urine/blood test for alcohol and drugs of abuse at Screening and on Day-1 * Use of prohibited medications or herbal remedies * Known presence or history of intestinal polyps * Known presence or history of any type of cancer * Pancreatic events such as acute pancreatitis, pancreatic duct stenosis, pancreas infection, and increased blood amylase and lipase (\>2.0-5.0×upper limit of normal range) * Participation in an investigational drug or device study within 30 days prior to Screening * Donation of blood over 500 mL within 2 months prior to Screening * Heavy use of tobacco products (i.e., smokes more than 10 cigarettes per day) * Concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this trial * Any intercurrent clinically significant illness in the previous 28 days before Day 1 of this study * Positive blood screen for human immunodeficiency virus (HIV) antigen/antibody combo, hepatitis A (HAV), hepatitis B surface antigen (HBsAgB), or hepatitis C virus (HCV) * Unwillingness or inability to comply with the study protocol for any other reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve to Infinity (AUCinf) of Apraglutide | Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose | Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a lower limit of quantification (LLOQ) of 1 ng/mL and an upper limit of 200 ng/mL. Plasma pharmacokinetic (PK) parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. AUCinf was calculated as: AUCinf = AUC from time zero to the last quantifiable concentration (AUClast) + (Clast/kel) where Clast was the observed concentration at the last time point with concentrations above the lower limit of quantification and kel was the terminal elimination rate constant. |
| Area Under the Curve (AUC) From Time Zero to 168 Hours Post-dose (AUC0-168h) of Apraglutide | Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, and 168 hours post-dose | Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. |
| Maximum Observed Plasma Concentration (Cmax) of Apraglutide | Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose | Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. Cmax was the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Half-life (t1/2) of Apraglutide | Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose | Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. |
| Time of Maximum Plasma Concentration (Tmax) of Apraglutide | Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose | Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. Tmax was the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Day 1 to Day 14 | A TEAE was any unfavorable and unintended sign, symptom, or disease temporally associated with apraglutide, whether or not related, that occurred or worsened after the dose of apraglutide. A serious TEAE was defined as any TEAE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were graded for severity based on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 as follows from Grade 1 (mild) to Grade 5 (AE resulted in death). Clinically significant changes in physical examination findings, laboratory results, vital signs, and 12-lead electrocardiograms (ECGs) were also recorded as TEAEs. |
| Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Apraglutide | Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose | Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. |
| Apparent Clearance After Extravascular Administration (CL/F) of Apraglutide | Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose | Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. |
| Terminal Elimination Rate Constant (Kel) of Apraglutide | Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose | Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. Terminal elimination rate constant calculated by linear regression of the terminal log-linear portion of the concentration vs. time curve. Linear regression of at least three points and an adjusted r\^2 greater than or equal to 0.80 were required to obtain a reliable kel. |
Countries
Germany, Slovakia
Participant flow
Recruitment details
Participants were enrolled in 2 study sites in Slovakia and Germany and participated from February 2023 to April 2023.
Pre-assignment details
In Part 1, participants with normal hepatic function were matched 1:1 for age (±10 years), body mass index (BMI; ±15%), and sex (1:1) to participants with moderate hepatic impairment. Part 2 was to be conducted dependent on the outcome of Part 1 and planned to enroll participants with mild hepatic impairment. No participants enrolled in Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Normal Hepatic Function Group Participants with normal hepatic function received a single SC dose of apraglutide on Day 1. | 8 |
| Moderate Hepatic Impairment Group Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Moderate Hepatic Impairment Group | Total | Normal Hepatic Function Group |
|---|---|---|---|
| Age, Continuous | 58.8 years | 58.5 years | 58.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 16 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Curve (AUC) From Time Zero to 168 Hours Post-dose (AUC0-168h) of Apraglutide
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used.
Time frame: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, and 168 hours post-dose
Population: The PK parameter set included participants who received at least one dose of apraglutide and who had at least one PK parameter of interest estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function Group | Area Under the Curve (AUC) From Time Zero to 168 Hours Post-dose (AUC0-168h) of Apraglutide | 4271 h*ng/mL | Geometric Coefficient of Variation 65.2 |
| Moderate Hepatic Impairment Group | Area Under the Curve (AUC) From Time Zero to 168 Hours Post-dose (AUC0-168h) of Apraglutide | 3605 h*ng/mL | Geometric Coefficient of Variation 50.2 |
Primary
Area Under the Curve to Infinity (AUCinf) of Apraglutide
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a lower limit of quantification (LLOQ) of 1 ng/mL and an upper limit of 200 ng/mL. Plasma pharmacokinetic (PK) parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. AUCinf was calculated as: AUCinf = AUC from time zero to the last quantifiable concentration (AUClast) + (Clast/kel) where Clast was the observed concentration at the last time point with concentrations above the lower limit of quantification and kel was the terminal elimination rate constant.
Time frame: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
Population: The PK parameter set included participants who received at least one dose of apraglutide and who had at least one PK parameter of interest estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function Group | Area Under the Curve to Infinity (AUCinf) of Apraglutide | 4481 h*ng/mL | Geometric Coefficient of Variation 64.5 |
| Moderate Hepatic Impairment Group | Area Under the Curve to Infinity (AUCinf) of Apraglutide | 3744 h*ng/mL | Geometric Coefficient of Variation 50.2 |
Comparison: Moderate Hepatic Impairment Group (test) versus Normal Hepatic Function Group (reference). The analysis was performed on natural log (ln) transformed parameters using an analysis of variance model with the hepatic function group as a fixed effect.90% CI: [0.5216, 1.338]
Primary
Maximum Observed Plasma Concentration (Cmax) of Apraglutide
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. Cmax was the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.
Time frame: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
Population: The PK parameter set included participants who received at least one dose of apraglutide and who had at least one PK parameter of interest estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function Group | Maximum Observed Plasma Concentration (Cmax) of Apraglutide | 58.3 ng/mL | Geometric Coefficient of Variation 68.3 |
| Moderate Hepatic Impairment Group | Maximum Observed Plasma Concentration (Cmax) of Apraglutide | 54.6 ng/mL | Geometric Coefficient of Variation 43.1 |
Comparison: Moderate Hepatic Impairment Group (test) versus Normal Hepatic Function Group (reference). The analysis was performed on ln transformed parameters using an analysis of variance model with the hepatic function group as a fixed effect.90% CI: [0.5889, 1.4864]
Secondary
Apparent Clearance After Extravascular Administration (CL/F) of Apraglutide
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used.
Time frame: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
Population: The PK parameter set included participants who received at least one dose of apraglutide and who had at least one PK parameter of interest estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function Group | Apparent Clearance After Extravascular Administration (CL/F) of Apraglutide | 1.12 L/h | Geometric Coefficient of Variation 64.5 |
| Moderate Hepatic Impairment Group | Apparent Clearance After Extravascular Administration (CL/F) of Apraglutide | 1.34 L/h | Geometric Coefficient of Variation 50.2 |
Secondary
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Apraglutide
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used.
Time frame: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
Population: The PK parameter set included participants who received at least one dose of apraglutide and who had at least one PK parameter of interest estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function Group | Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Apraglutide | 53.4 liters | Geometric Coefficient of Variation 91.1 |
| Moderate Hepatic Impairment Group | Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Apraglutide | 56.2 liters | Geometric Coefficient of Variation 69.4 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE was any unfavorable and unintended sign, symptom, or disease temporally associated with apraglutide, whether or not related, that occurred or worsened after the dose of apraglutide. A serious TEAE was defined as any TEAE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were graded for severity based on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 as follows from Grade 1 (mild) to Grade 5 (AE resulted in death). Clinically significant changes in physical examination findings, laboratory results, vital signs, and 12-lead electrocardiograms (ECGs) were also recorded as TEAEs.
Time frame: Day 1 to Day 14
Population: The safety analysis set included all participants who received at least one dose of apraglutide.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Normal Hepatic Function Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | At least one TEAE | 0 Participants |
| Normal Hepatic Function Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | At least one serious TEAE | 0 Participants |
| Normal Hepatic Function Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | At least one TEAE leading to discontinuation | 0 Participants |
| Normal Hepatic Function Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any mild TEAE | 0 Participants |
| Normal Hepatic Function Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any moderate TEAE | 0 Participants |
| Normal Hepatic Function Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any related TEAE | 0 Participants |
| Moderate Hepatic Impairment Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any moderate TEAE | 1 Participants |
| Moderate Hepatic Impairment Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | At least one TEAE | 1 Participants |
| Moderate Hepatic Impairment Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any mild TEAE | 1 Participants |
| Moderate Hepatic Impairment Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | At least one serious TEAE | 0 Participants |
| Moderate Hepatic Impairment Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any related TEAE | 1 Participants |
| Moderate Hepatic Impairment Group | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | At least one TEAE leading to discontinuation | 0 Participants |
Secondary
Terminal Elimination Rate Constant (Kel) of Apraglutide
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. Terminal elimination rate constant calculated by linear regression of the terminal log-linear portion of the concentration vs. time curve. Linear regression of at least three points and an adjusted r\^2 greater than or equal to 0.80 were required to obtain a reliable kel.
Time frame: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
Population: The PK parameter set included participants who received at least one dose of apraglutide and who had at least one PK parameter of interest estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function Group | Terminal Elimination Rate Constant (Kel) of Apraglutide | 0.0209 1/h | Geometric Coefficient of Variation 51.6 |
| Moderate Hepatic Impairment Group | Terminal Elimination Rate Constant (Kel) of Apraglutide | 0.0237 1/h | Geometric Coefficient of Variation 44.4 |
Secondary
Terminal Half-life (t1/2) of Apraglutide
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used.
Time frame: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
Population: The PK parameter set included participants who received at least one dose of apraglutide and who had at least one PK parameter of interest estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function Group | Terminal Half-life (t1/2) of Apraglutide | 33.2 hours | Geometric Coefficient of Variation 51.6 |
| Moderate Hepatic Impairment Group | Terminal Half-life (t1/2) of Apraglutide | 29.2 hours | Geometric Coefficient of Variation 44.4 |
Secondary
Time of Maximum Plasma Concentration (Tmax) of Apraglutide
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. Tmax was the first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units.
Time frame: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
Population: The PK parameter set included participants who received at least one dose of apraglutide and who had at least one PK parameter of interest estimated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Hepatic Function Group | Time of Maximum Plasma Concentration (Tmax) of Apraglutide | 32.03 hours |
| Moderate Hepatic Impairment Group | Time of Maximum Plasma Concentration (Tmax) of Apraglutide | 31.76 hours |