Clinical trial NCT03279302: Trial to Evaluate the PK Profile of Glepaglutide (ZP1848) After a Single IV and After Multiple SC Injections in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
First posted: 2017-09-12
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic parameter - half life
timeFrame: Day 0 up to Day 73
measure: Pharmacokinetic parameter - total body clearance
timeFrame: Day 0 to Day 22
measure: Pharmacokinetic parameter - Apparent clearance
timeFrame: Day 0 to Day 73
measure: Pharmacokinetic parameter - Volume of distribution
timeFrame: Day 0- Day 22
measure: Pharmacokinetic parameter - apparent volume of distribution
timeFrame: Day 0 to Day 73
Secondary outcomes:
measure: Pharmacokinetic parameter - Cmax
timeFrame: Day 0 to Day 73
measure: Pharmacokinetic parameter - tmax
timeFrame: Day 0 to Day 73
measure: Pharmacokinetic parameter - AUC
timeFrame: Day 0 to Day 73
measure: Pharmacodynamic parameter - plasma citrulline levels
timeFrame: Day 0 to Day 73
measure: ADA incidence
timeFrame: Day 0 to Day 73
measure: Safety and tolerability - AEs
timeFrame: Day 0 to Day 73
measure: Safety and tolerability - ECGs
timeFrame: Day 0 to Day 73
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance CRU
state: Texas
Study officials:
References:
citation: 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.