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Completed

NCT Number: NCT05706623

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

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.

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Key information

Conditions

Hepatic Impairment

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

APEX, Münich, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Apraglutide

Drug

Single dose of apraglutide

Primary outcomes

  1. Area Under the Curve to Infinity (AUCinf) of Apraglutide

    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

    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.

  2. Area Under the Curve (AUC) From Time Zero to 168 Hours Post-dose (AUC0-168h) of Apraglutide

    Time frame: 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.

  3. Maximum Observed Plasma Concentration (Cmax) of Apraglutide

    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

    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 outcomes

  1. Time of Maximum Plasma Concentration (Tmax) of Apraglutide

    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

    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.

  2. Apparent Clearance After Extravascular Administration (CL/F) of Apraglutide

    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

    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.

  3. Terminal Elimination Rate Constant (Kel) of Apraglutide

    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

    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.

  4. Terminal Half-life (t1/2) of Apraglutide

    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

    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.

  5. Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Apraglutide

    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

    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.

  6. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

VectivBio AG

Industry

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Jan 31, 2023
Registry last updated
Jul 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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