Trial Outcomes & Findings for A Phase 1 Open-Label Evaluation of the Pharmacokinetics and Safety of a Single Dose of Apraglutide in Subjects With Normal and Impaired Hepatic Function (NCT NCT05706623)
NCT ID: NCT05706623
Last Updated: 2025-07-10
Results Overview
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.
COMPLETED
PHASE1
16 participants
Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose
2025-07-10
Participant Flow
Participants were enrolled in 2 study sites in Slovakia and Germany and participated from February 2023 to April 2023.
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.
Participant milestones
| Measure |
Normal Hepatic Function Group
Participants with normal hepatic function received a single subcutaneous (SC) dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
Dosed With Apraglutide
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Phase 1 Open-Label Evaluation of the Pharmacokinetics and Safety of a Single Dose of Apraglutide in Subjects With Normal and Impaired Hepatic Function
Baseline characteristics by cohort
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.3 years
n=5 Participants
|
58.8 years
n=7 Participants
|
58.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Area Under the Curve to Infinity (AUCinf) of Apraglutide
|
4481 h*ng/mL
Geometric Coefficient of Variation 64.5
|
3744 h*ng/mL
Geometric Coefficient of Variation 50.2
|
PRIMARY outcome
Timeframe: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, and 168 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
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
|
3605 h*ng/mL
Geometric Coefficient of Variation 50.2
|
PRIMARY outcome
Timeframe: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Apraglutide
|
58.3 ng/mL
Geometric Coefficient of Variation 68.3
|
54.6 ng/mL
Geometric Coefficient of Variation 43.1
|
SECONDARY outcome
Timeframe: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Apraglutide
|
32.03 hours
Interval 27.97 to 48.15
|
31.76 hours
Interval 12.0 to 36.0
|
SECONDARY outcome
Timeframe: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Apparent Clearance After Extravascular Administration (CL/F) of Apraglutide
|
1.12 L/h
Geometric Coefficient of Variation 64.5
|
1.34 L/h
Geometric Coefficient of Variation 50.2
|
SECONDARY outcome
Timeframe: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Terminal Elimination Rate Constant (Kel) of Apraglutide
|
0.0209 1/h
Geometric Coefficient of Variation 51.6
|
0.0237 1/h
Geometric Coefficient of Variation 44.4
|
SECONDARY outcome
Timeframe: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Terminal Half-life (t1/2) of Apraglutide
|
33.2 hours
Geometric Coefficient of Variation 51.6
|
29.2 hours
Geometric Coefficient of Variation 44.4
|
SECONDARY outcome
Timeframe: Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Apraglutide
|
53.4 liters
Geometric Coefficient of Variation 91.1
|
56.2 liters
Geometric Coefficient of Variation 69.4
|
SECONDARY outcome
Timeframe: Day 1 to Day 14Population: The safety analysis set included all participants who received at least one dose of apraglutide.
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.
Outcome measures
| Measure |
Normal Hepatic Function Group
n=8 Participants
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 Participants
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
At least one TEAE
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
At least one serious TEAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
At least one TEAE leading to discontinuation
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Any mild TEAE
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Any moderate TEAE
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Any related TEAE
|
0 Participants
|
1 Participants
|
Adverse Events
Normal Hepatic Function Group
Moderate Hepatic Impairment Group
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Normal Hepatic Function Group
n=8 participants at risk
Participants with normal hepatic function received a single SC dose of apraglutide on Day 1.
|
Moderate Hepatic Impairment Group
n=8 participants at risk
Participants with moderate hepatic impairment received a single SC dose of apraglutide on Day 1.
|
|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/8 • Day 1 to Day 14
The safety analysis set included all participants who received at least one dose of apraglutide.
|
12.5%
1/8 • Day 1 to Day 14
The safety analysis set included all participants who received at least one dose of apraglutide.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/8 • Day 1 to Day 14
The safety analysis set included all participants who received at least one dose of apraglutide.
|
12.5%
1/8 • Day 1 to Day 14
The safety analysis set included all participants who received at least one dose of apraglutide.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place