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

NCT03279302 | Completed Phase 1 FDA Drug

• 1 other identifier: ZP1848-16182
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (7)

• Pharmacokinetic parameter - Cmax

  Day 0 to Day 73

• Pharmacokinetic parameter - tmax

  Day 0 to Day 73

• Pharmacokinetic parameter - AUC

  Day 0 to Day 73

• Pharmacodynamic parameter - plasma citrulline levels

  Day 0 to Day 73

• ADA incidence

  Day 0 to Day 73

Study Arms (5)

Group A

EXPERIMENTAL

1 mg glepaglutide once daily, given as single SC injections on Days 1 to 7

Drug: Glepaglutide

Group B

EXPERIMENTAL

5 mg glepaglutide once daily, given as single SC injections on Days 1 to 7

Drug: Glepaglutide

Group C

EXPERIMENTAL

5 mg glepaglutide once weekly, given as single SC injections on Days 1, 8, 15, 22, 29, and 36

Drug: Glepaglutide

Group D

EXPERIMENTAL

10 mg glepaglutide once weekly, given as single SC injections on Days 1, 8, 15, 22, 29, and 36

Drug: Glepaglutide

Group E

EXPERIMENTAL

1 mg glepaglutide, given as an IV infusion at a rate of 4 mg/h for 15 minutes on Day 1

Drug: Glepaglutide

Interventions

Glepaglutide DRUG

Solution for injection

Also known as: ZP1848

Group A; Group B; Group C; Group D; Group E

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zealand Pharma: lead

Study Sites (1)

Covance CRU

Dallas, Texas, 75247, United States

Location

Related Publications (1)

• 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.

  PMID: 36323988 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 12, 2017
• Study Start: September 4, 2017
• Primary Completion: December 18, 2017
• Study Completion: December 18, 2017
• Last Updated: December 22, 2017

Record last verified: 2017-12

Locations

US (1)