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

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: Glepaglutide

• Registration Number: NCT03279302
• Lead Sponsor: Zealand Pharma

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2017-09-04
• Study First Submitted: 2017-09-05
• Study First Submitted QC: 2017-09-08
• Study First Posted: 2017-09-12
• Status Verified: 2017-12
• Primary Completion: 2017-12-18
• Study Completion: 2017-12-18
• Last Update Submitted: 2017-12-21
• Last Update Posted: 2017-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group C	Glepaglutide	5 mg glepaglutide once weekly, given as single SC injections on Days 1, 8, 15, 22, 29, and 36
Group B	Glepaglutide	5 mg glepaglutide once daily, given as single SC injections on Days 1 to 7
Group E	Glepaglutide	1 mg glepaglutide, given as an IV infusion at a rate of 4 mg/h for 15 minutes on Day 1
Group A	Glepaglutide	1 mg glepaglutide once daily, given as single SC injections on Days 1 to 7
Group D	Glepaglutide	10 mg glepaglutide once weekly, given as single SC injections on Days 1, 8, 15, 22, 29, and 36

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Covance CRU; 🇺🇸 Dallas, Texas, United States