Relative Bioavailability of a New Presentation of Apraglutide Versus the Reference Formulation

Study Overview
=================
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.

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

Conditions
-----------------
Healthy Subjects

Intervention / Treatment
-----------------
* Drug: Apraglutide


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 67 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single SC dose of 5 mg from DCS<br> | Drug: Apraglutide<br>* Peptide analogue of GLP-2<br>|
| Experimental: Two concomitant single SC doses of 2.5 mg from DCS<br> | Drug: Apraglutide<br>* Peptide analogue of GLP-2<br>|
| Active Comparator: Single SC dose of 5 mg from vial<br> | Drug: Apraglutide<br>* Peptide analogue of GLP-2<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma apraglutide primary PK parameter: Maximum observed plasma concentration (Cmax) |  | 0 to 312 hours post dose in each period | 
| Plasma apraglutide primary PK parameter: AUCinf or AUClast |  | 0 to 312 hours post dose in each period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of maximum plasma concentration (tmax) |  | 0 to 312 hours post dose in each period | 
| Terminal elimination rate constant (λz) |  | 0 to 312 hours post dose in each period | 
| Terminal half-life (t½) |  | 0 to 312 hours post dose in each period | 
| Incidence, nature and severity of adverse events (AE) with apraglutide |  | Baseline to Day 79 | 
| 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. | Baseline to Day 79 | 
| 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. | Baseline to Day 79 | 
| Hemostasis | Hemostasis INR will be examined for clinically significant changes. INR levels will be listed by subject. Descriptive statistics will be used to assess any changes in hemostasis results during and following trial treatment administration. Values outside the reference ranges will be highlighted and clinical significance stated. | Baseline to Day 79 | 
| Anti-drug antibodies (ADA) analysis | ADA will be will be examined for clinically significant changes | Baseline to Day 79 | 
| Urine analysis | Urine analysis panel of analytes will be examined for clinically significant changes. Urine analysis data 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. | Baseline to Day 79 | 
| Occurrence of clinically relevant changes in electrocardiogram | ECG QT Interval | Baseline to Day 79 | 
| Occurrence of clinically relevant changes in electrocardiogram | ECG PR interval | Baseline to Day 79 | 
| Occurrence of clinically relevant changes in electrocardiogram | ECG QRS interval | Baseline to Day 79 | 
| Occurrence of clinically relevant changes in electrocardiogram | ECG rhythm | Baseline to Day 79 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Relative bioavailability, Dual-chamber syringe