Evaluation of Apraglutide on Gastric Emptying

A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Single Center, Multiple-Dose, Parallel Trial Evaluating the Impact of Apraglutide on Gastric Emptying of Liquids in Healthy Subjects

The primary objective is to assess the effect of apraglutide on gastric emptying of liquids in healthy subjects, as measured by the PK of acetaminophen mixed with a liquid meal.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Apraglutide; Drug: Acetaminophen; Drug: Placebo

Detailed Description

This is a single-center, double-blind, randomized, multiple-dose, parallel trial with a total duration of up to 50 days. The trial population will consist of healthy volunteers. Eligible subjects will be randomized to receive either subcutaneous (SC) apraglutide or matching placebo. The effect of apraglutide on gastric emptying of liquids will be assessed by the measure of PK of acetaminophen mixed with a liquid meal.

There will be two treatment periods, occurring according to the same sequence. In Period 1 acetaminophen will be given on Day 1, apraglutide/placebo will be injected on Day2. In Period 2 apraglutide/placebo will be injected on Day 9 and acetaminophen will be given on Day 10. This will allow to assess the PK of acetaminophen without the effect of apraglutide in Period 1, and to assess the PK of acetaminophen at the maximum concentration of apraglutide in Period 2.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • ICON Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age between 18 and 45 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 ≥18.0 to ≤30.0 kg/m2; and a total body weight of >50 kg (110 lb).
• Women of childbearing potential (WOCBP) having undergone bilateral tubal occlusion or with vasectomized partner. Sterilized or infertile or postmenopausal females.
• Male subjects with a WOCBP partner using highly effective methods of contraception and agreeing on no sperm donation during the trial and for 2 weeks after (EOT) visit.

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 WOCBP, a positive urine/blood pregnancy test
• Breast-feeding women
• Positive urine/blood test for alcohol and drugs of abuse
• 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
• Use of tobacco products (i.e., smokes more than 5 cigarettes per day or equivalent)
• 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 IGM), hepatitis B surface antigen (HBsAgB), or hepatitis C virus (HCV)
• Unwillingness or inability to comply with the study protocol for any other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Acetaminophen; Acetaminophen mixed with a liquid meal; Drug: Placebo; Matching placebo to apraglutide
Experimental: Apraglutide SC injections	Drug: Apraglutide; Peptide analogue of GLP-2; Drug: Acetaminophen; Acetaminophen mixed with a liquid meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration (Cmax) of acetaminophen	0-300 Minutes
Time at which the maximum plasma concentration is observed (tmax) of acetaminophen	0-300 Minutes
Area under the acetaminophen concentration-time curve: AUCinf (AUClast in case AUCinf cannot be estimated)	0-14 hours
Area under the acetaminophen concentration-time curve: AUC0-300min	0-300 Minutes
Area under the acetaminophen concentration-time curve: AUC0-60min	0-60 Minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height	In cm	Through study completion, up to 24 days
Weight	In kg	Through study completion, up to 24 days
Physical examination	Clinically significant outcome (as normal or abnormal) for physical examination of eyes, neurological, gastrointestinal, respiratory, circulatory, muscular, cardiovascular, lymphatic, ears, nose, throat.	Through study completion, up to 24 days
The incidence, nature and severity of adverse events (AEs) with apraglutide		Through study completion, up to 24 days
Clinical chemistry	Clinical Chemistry panel of analytes will be examined for clinically significant changes. Clinical chemistry analytes will be listed by subject. Descriptive statistics will be used to assess any changes in clinical laboratory results during and following trial treatment administration. Values outside the reference ranges will be highlighted and clinical significance stated.	Through study completion, up to 24 days
Hematology	Hematology panel of analytes will be examined for clinically significant changes. Hematology analytes will be listed by subject. Descriptive statistics will be used to assess any changes in clinical laboratory results during and following trial treatment administration. Values outside the reference ranges will be highlighted and clinical significance stated.	Through study completion, up to 24 days
Hemostasis	Hemostasis INR will be examined for clinically significant changes	Through study completion, up to 24 days
Anti-drug antibodies (ADA) analysis	ADA will be will be examined for clinically significant changes	Through study completion, up to 24 days
Urine analysis	Urine analysis panel of analytes will be examined for clinically significant changes	Through study completion, up to 24 days
Occurrence of clinically relevant changes in vital signs	Systolic and diastolic blood pressure in mmHg	Through study completion, up to 24 days
Occurrence of clinically relevant changes in vital signs	Pulse rate in Beats per Minute	Through study completion, up to 24 days
Changes in body temperature in °C		Through study completion, up to 24 days
Occurrence of clinically relevant changes in electrocardiogram	ECG QT Interval	Through study completion, up to 24 days
Occurrence of clinically relevant changes in electrocardiogram	ECG PR interval	Through study completion, up to 24 days
Occurrence of clinically relevant changes in electrocardiogram	ECG QRS interval	Through study completion, up to 24 days
Occurrence of clinically relevant changes in electrocardiogram	ECG rhythm	Through study completion, up to 24 days

Collaborators and Investigators

• Sponsor: VectivBio AG
• Investigators: Study Director: Tomasz Masior, VectivBio AG

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2023
• Primary Completion (Actual): July 24, 2023
• Study Completion (Actual): July 24, 2023

Study Registration Dates

• First Submitted: February 22, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 16, 2023

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Gastric emptying; Pharmacokinetics of acetaminophen
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Acetaminophen
• Other Study ID Numbers: TA799-020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No