Evaluation of Apraglutide on Gastric Emptying

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Apraglutide
* Drug: Placebo
* Drug: Acetaminophen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric emptying, Pharmacokinetics of acetaminophen