Healthy Subjects
Conditions
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
Interventions
DRUGGlepaglutide
Solution for injection
Sponsors
Zealand Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameter - half life | Day 0 up to Day 73 | Half life of glepaglutide and active metabolites |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ADA incidence | Day 0 to Day 73 | Overall incidence of anti-glepaglutide antibodies |
| Safety and tolerability - ECGs | Day 0 to Day 73 | 12 lead electrocardiogram parameters |
| 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 - Cmax | Day 0 to Day 73 | Maximum observed plasma concentration |
| Pharmacokinetic parameter - tmax | Day 0 to Day 73 | time of maximum observed plasma concentration |
| Pharmacokinetic parameter - AUC | Day 0 to Day 73 | Area under the curve |
| Pharmacodynamic parameter - plasma citrulline levels | Day 0 to Day 73 | change in plasma citrulline levels |
Countries
United States
Outcome results
None listed