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

Hepatic Impairment Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05706623
• Other study ID #: TA799-015
• Status: Completed
• Phase: Phase 1
• Start date: January 30, 2023
• Est. completion date: April 4, 2023

Study information

• Verified date: July 2023
• Source: VectivBio AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to assess the PK of apraglutide in subjects with hepatic impairment compared with matched control subjects with normal hepatic function following single SC dose administration.

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 5 mg 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 AUCinf or AUClast for the moderate hepatic impairment group compared to the control group is ≥2.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 4, 2023
• Est. primary completion date: April 4, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Apraglutide
Single dose of apraglutide 5mg.

Locations

Country	Name	City	State
Germany	APEX	Münich
Slovakia	Summit Clinical Research	Bratislava

Sponsors (1)

Lead Sponsor	Collaborator
VectivBio AG

Countries where clinical trial is conducted

Germany,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma apraglutide primary PK parameter: AUCinf or AUClast	Area under the curve to infinity (AUCinf) or area under the curve from time zero to the last quantifiable concentration (AUClast) if AUCinf cannot be reliably estimated	0 to 312 hours
Primary	Plasma apraglutide primary PK parameter: AUC0-168h	Area under the curve from time zero to 168 hours after apraglutide administration (AUC0-168h)	0 to 168 hours
Primary	Maximum observed plasma concentration (Cmax)		0 to 168 hours
Secondary	Time of maximum plasma concentration (tmax)		0 to 168 hours
Secondary	Apparent clearance after extravascular administration (CL/F)		0 to 168 hours
Secondary	Apparent volume of distribution after extravascular administration (Vz/F)		0 to 168 hours
Secondary	Terminal elimination rate constant (?z)		0 to 168 hours
Secondary	Terminal half-life (t½)		0 to 168 hours
Secondary	Incidence, nature,and severity of adverse events (AE) with apraglutide		Baseline to Day 16