Trial to Evaluate the PK Profile of Glepaglutide (ZP1848) After a Single IV and After Multiple SC Injections in Healthy Subjects

Study Overview
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Brief Summary
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The primary objective of the trial is to characterize the pharmacokinetic (PK) profiles of glepaglutide and its primary active metabolites following once-daily and once-weekly subcutaneous (SC) injections and after a single intravenous (IV) infusion in healthy subjects. Glepaglutide is a proposed International Nonproprietary Name for ZP1848

Official Title
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A Phase 1, Open-Label, Partially Randomized, 3-Part, Parallel Group Trial to Evaluate the Pharmacokinetic Profile of Glepaglutide (ZP1848) After a Single Intravenous Injection and After Multiple Subcutaneous Injections in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Glepaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations Body Mass index between 18 and 30.0 kg/m2 Able to comply with all the trial procedures females will not be pregnant or lactating If female of childbearing potential or male agree to use contraception as defined in the protocol Male subjects must also be willing to refrain from donating sperm from trial Check-in until 90 days after the last dose Exclusion Criteria: Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance History of bowel obstruction, stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and/or cholecystectomy or hernia repair will be allowed). Clinically significant abnormality on 12-lead ECG Clinically significant abnormality in hematology, clinical chemistry, or urinalysis History of alcoholism or drug/chemical abuse within 2 years Alcohol consumption of > 21 units per week for males and > 14 units for females Positive urine drug screen Positive hepatitis panel and/or positive human immunodeficiency test Receipt of any investigational product within 30 days or 5 half-lives Previous exposure to GLP-1, GLP-2, human growth hormone, or analogs thereof 30 days prior to Check-in Use or intend to use any medications/products known to be strong inhibitors or strong inducers of cytochrome P450 3A enzyme, including St. John's wort Use of tobacco, smoking cessation products, or products containing nicotine (including but not limited to cigarettes, e-cigarettes, pipes, cigars, chewing tobacco, nicotine lozenges, or nicotine gum ) within 3 months prior to Screening Receipt of blood products within 2 months prior to Check-in and throughout the trial. Donation of blood or significant blood loss from 56 days prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening and throughout the trial. Poor peripheral venous access.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>1 mg glepaglutide once daily, given as single SC injections on Days 1 to 7 | Drug: Glepaglutide<br>* Solution for injection<br>* Other names: ZP1848;|
| Experimental: Group B<br>5 mg glepaglutide once daily, given as single SC injections on Days 1 to 7 | Drug: Glepaglutide<br>* Solution for injection<br>* Other names: ZP1848;|
| Experimental: Group C<br>5 mg glepaglutide once weekly, given as single SC injections on Days 1, 8, 15, 22, 29, and 36 | Drug: Glepaglutide<br>* Solution for injection<br>* Other names: ZP1848;|
| Experimental: Group D<br>10 mg glepaglutide once weekly, given as single SC injections on Days 1, 8, 15, 22, 29, and 36 | Drug: Glepaglutide<br>* Solution for injection<br>* Other names: ZP1848;|
| Experimental: Group E<br>1 mg glepaglutide, given as an IV infusion at a rate of 4 mg/h for 15 minutes on Day 1 | Drug: Glepaglutide<br>* Solution for injection<br>* Other names: ZP1848;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter - half life | Half life of glepaglutide and active metabolites | Day 0 up to Day 73 | 
| Pharmacokinetic parameter - total body clearance | Total body clearance after IV administration | Day 0 to Day 22 | 
| Pharmacokinetic parameter - Apparent clearance | CL/F for subcutaneous doses | Day 0 to Day 73 | 
| Pharmacokinetic parameter - Volume of distribution | Volume of distribution after IV dosing | Day 0- Day 22 | 
| Pharmacokinetic parameter - apparent volume of distribution | Vss/F and Vz/F for subcutaneous doses | Day 0 to Day 73 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter - Cmax | Maximum observed plasma concentration | Day 0 to Day 73 | 
| Pharmacokinetic parameter - tmax | time of maximum observed plasma concentration | Day 0 to Day 73 | 
| Pharmacokinetic parameter - AUC | Area under the curve | Day 0 to Day 73 | 
| Pharmacodynamic parameter - plasma citrulline levels | change in plasma citrulline levels | Day 0 to Day 73 | 
| ADA incidence | Overall incidence of anti-glepaglutide antibodies | Day 0 to Day 73 | 
| Safety and tolerability - AEs | Incidence, nature, and severity of adverse events, abnormal clinical laboratory tests, and injection site reactions | Day 0 to Day 73 | 
| Safety and tolerability - ECGs | 12 lead electrocardiogram parameters | Day 0 to Day 73 |