Clinical trial NCT06002555: Relative Bioavailability of a New Presentation of Apraglutide Versus the Reference Formulation
Official title: A Randomized Open-label, Single Dose, 3-Period, 6-Sequence, Cross-Over Trial With Washout Periods of at Least 14 Days to Investigate the Relative Bioavailability of Apraglutide in Dual Chamber Syringes Versus the Reference Formulation in Vials Following Subcutaneous Administrations in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Relative bioavailability
Dual-chamber syringe
Lead sponsor: VectivBio AG
Sponsor class: INDUSTRY
First posted: 2023-08-21
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 67
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This trial compares the relative bioavailability of apraglutide in dual-chamber syringes (DCS) versus the reference formulation apraglutide in vials.

Detailed description: This is a single-center, open-label, randomized, three-period, and six-sequence cross-over trial with two washout periods of at least 14 days to compare the relative bioavailability of apraglutide using DCS versus the reference formulation in vials, following SC administrations in healthy male and female subjects.

Following consent, subjects will undergo a Screening procedure to see if they are suitable to be enrolled in the trial. Screening may be performed up to 28 days prior to the first injection procedure. All eligible subjects will receive the following treatments in three separate treatment periods:

* Treatment A: Single SC dose of 5 mg (400 µL) from DCS at a concentration of 12.5 mg/mL
* Treatment B: Two concomitant single SC doses of 2.5 mg (400 µL each) of DCS at a concentration of 6.25 mg/mL
* Treatment C: Single SC dose of 5 mg (200 µL) from vial at a concentration of 25 mg/mL of the current formulation-reference There will be a 14-day washout period between the first and second treatment periods and between the second and third treatment periods.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 67 years inclusive
* Subjects 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 ≤35.0 kg/m2; and a total body weight of \>50 kg
* 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 4 weeks after (EOT) visit.

Exclusion Criteria:

* History of clinically significant gastrointestinal, bronchopulmonary, neurological, cardiovascular, endocrine, or allergic disease
* Known hypersensitivity to the investigational medicinal products (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 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) at Screening or on Day -1 of each period
* Participation in an investigational drug or device study within 30 days prior to screening
* Donation of blood over 500 mL within 3 months prior to screening
* Use of tobacco products (i.e., smokes more than 10 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), hepatitis B core antigen (anti-HBc) or hepatitis C virus (HCV)
* Unwillingness or inability to comply with the study protocol for any other reason

Primary outcomes:
measure: Plasma apraglutide primary PK parameter: Maximum observed plasma concentration (Cmax)
timeFrame: 0 to 312 hours post dose in each period
measure: Plasma apraglutide primary PK parameter: AUCinf or AUClast
timeFrame: 0 to 312 hours post dose in each period
Secondary outcomes:
measure: Time of maximum plasma concentration (tmax)
timeFrame: 0 to 312 hours post dose in each period
measure: Terminal elimination rate constant (λz)
timeFrame: 0 to 312 hours post dose in each period
measure: Terminal half-life (t½)
timeFrame: 0 to 312 hours post dose in each period
measure: Incidence, nature and severity of adverse events (AE) with apraglutide
timeFrame: Baseline to Day 79
measure: Clinical chemistry
timeFrame: Baseline to Day 79
measure: Hematology
timeFrame: Baseline to Day 79
measure: Hemostasis
timeFrame: Baseline to Day 79
measure: Anti-drug antibodies (ADA) analysis
timeFrame: Baseline to Day 79
measure: Urine analysis
timeFrame: Baseline to Day 79
measure: Occurrence of clinically relevant changes in electrocardiogram
timeFrame: Baseline to Day 79
measure: Occurrence of clinically relevant changes in electrocardiogram
timeFrame: Baseline to Day 79
measure: Occurrence of clinically relevant changes in electrocardiogram
timeFrame: Baseline to Day 79
measure: Occurrence of clinically relevant changes in electrocardiogram
timeFrame: Baseline to Day 79
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: ICON Clinical Research Unit
Study officials:
affiliation: VectivBio AG
name: Tomasz Masior
role: STUDY_DIRECTOR
References: