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

NCT05706623 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TA799-015
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 2

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.

Conditions

Hepatic Impairment

Keywords

Hepatic Impairment; Liver Function; Hepatic Function

Outcome Measures

Primary Outcomes (3)

• 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.

  Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose

• 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.

  Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, and 168 hours post-dose

• 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.

  Pre-dose Day 1; 6, 12, 24, 28, 36, 40, 48, 60, 72, 96, 120, 144, 168, 240, and 312 hours post-dose

Secondary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

Part 1: Moderate hepatic impairment

EXPERIMENTAL

Child-Pugh B

Drug: Apraglutide

Part 1: Normal hepatic function

EXPERIMENTAL

Drug: Apraglutide

Part 2: Mild hepatic impairment

EXPERIMENTAL

Child-Pugh A

Drug: Apraglutide

Interventions

Apraglutide DRUG

Single dose of apraglutide

Part 1: Moderate hepatic impairment; Part 1: Normal hepatic function; Part 2: Mild hepatic impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• VectivBio AG: lead

Study Sites (2)

APEX

Münich, Germany

Location

Summit Clinical Research

Bratislava, Slovakia

Location

MeSH Terms

Interventions

apraglutide

Limitations and Caveats

Part 2 was to be conducted if the geometric mean ratio (GMR) point estimate of apraglutide AUCinf or AUClast for the moderate hepatic impairment group compared with the control group was ≥2. As the GMR point estimate of AUCinf was \<2, the trial stopped after Part 1.

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: VectivBio AG

ClinicalTrialEnquiries@ironwoodpharma.com

617.621.7722

Study Officials

• Tomasz Masior

  VectivBio AG

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: January 31, 2023
• Study Start: January 30, 2023
• Primary Completion: April 4, 2023
• Study Completion: April 4, 2023
• Last Updated: July 10, 2025
• Results First Posted: June 13, 2025

Record last verified: 2025-06

Locations

SL (1); DE (1)