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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Glepaglutide

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance CRU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zealand Pharma

Publications and helpful links

General Publications

• Agersnap MA, Sonne K, Knudsen KM, Knudsen CB, Berner-Hansen M. Pharmacokinetics of Glepaglutide, A Long-Acting Glucagon-Like Peptide-2 Analogue: A Study in Healthy Subjects. Clin Drug Investig. 2022 Dec;42(12):1093-1100. doi: 10.1007/s40261-022-01210-1. Epub 2022 Nov 2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 4, 2017
• Primary Completion (ACTUAL): December 18, 2017
• Study Completion (ACTUAL): December 18, 2017

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 8, 2017
• First Posted (ACTUAL): September 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 22, 2017
• Last Update Submitted That Met QC Criteria: December 21, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: ZP1848-16182

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No