Pharmacokinetic Profile of Glepaglutide After a Single Injection in Subjects With Varying Degrees of Renal Function

NCT04178447 | Completed Phase 1 FDA Drug

• 2 other identifiers: ZP1848-181312019-001466-15
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 3

Brief Summary

This is two stage design, open-label, multi-center, non-randomized trial evaluating the PK of a single, subcutaneous dose of 10 mg glepaglutide in subjects with varying degrees of renal function. The renal function will be calculated by the estimated glomerular filtration rate (eGFR) according to the Modification of Diet in Renal Disease (MDRD) equation.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic Variables

  AUC0-168 area under the concentration-time curve (AUC) from time 0 to 168 hours Cmax maximum observed plasma concentration

  11 days

Secondary Outcomes (1)

• Safety Variables

  11 days

Study Arms (4)

Group 1: ESRD subjects not on dialysis or severe RI

EXPERIMENTAL

subjects with eGFR \<15 mL/min/1.73 m2) or (eGFR 15 to \<30 mL/min/1.73 m2)

Drug: Glepaglutide

Group 2: normal renal function

EXPERIMENTAL

subjects with eGFR ≥90 mL/min/1.73 m2

Drug: Glepaglutide

Group 3: moderate RI

EXPERIMENTAL

subjects with eGFR 30 to \<60 mL/min/1.73 m2

Drug: Glepaglutide

Group 4: mild RI

EXPERIMENTAL

subjects with eGFR 60 to \<90 mL/min/1.73 m2

Drug: Glepaglutide

Interventions

Glepaglutide DRUG

Single dose of Glepaglutide 10 mg

Also known as: ZP1848

Group 1: ESRD subjects not on dialysis or severe RI; Group 2: normal renal function; Group 3: moderate RI; Group 4: mild RI

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects
• Able to understand and willing to sign the informed consent
• eGFR values as defined in in the arms
• Willing and able to comply with the study requirements
• Male and female subjects age 18 to 70 years (both inclusive) at the time of informed consent
• BMI 20.0 - 30.0 kg/m2 both inclusive
• Must be willing to comply with the contraception, sperm-donation requirements, and study restrictions.
• Renally Impaired Subjects (in Addition)
• Subject has a stable disease, including disease(s) associated with renal impairment, under medical control (ie, no changes in medication within 30 days prior to study drug administration). Stable renal impairment, defined as no clinically significant change in disease status within 3 months before screening.

You may not qualify if:

• All Subjects
• Suspicion of hypersensitivity, intolerance, or allergy to glepaglutide
• History of alcohol or drug abuse
• Clinically relevant abnormal medical history, abnormal findings on physical examination, vital signs, clinically significant abnormalities on 12-lead ECG, or laboratory tests at Screening that the Investigator judges as likely to interfere with the objectives of the study or the safety of the subject except for conditions associated with renal impairment in subjects with renal impairment
• Uncontrolled treated/untreated hypertension (defined as a mean of 3 repeated measurements for systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg); current or documented history of repeated clinically significant hypotension or severe episodes of orthostatic hypotension (systolic blood pressure \< 90 mmHg and/or diastolic blood pressure \< 50 mmHg)
• Acute illness within 14 days prior to dosing unless mild in severity and approved by the Investigator and Sponsor's medical representative
• Presence of active infection requiring antibiotics. Ingestion of alcohol within 72 hours prior to study drug administration and during PK sampling period including Follow-Up
• Participation in another investigational drug study within 30 days prior to study drug administration or exposure to more than three new investigational agents within 12 months prior to study drug administration
• Previous exposure to GLP-1, GLP-2, human growth hormone, somatostatin, or analogues thereof within 3 months prior to Screening. Use of dipeptidyl peptidase-4 inhibitors within 3 months prior to Screening
• Previous exposure to glepaglutide
• Donation or loss of more than 450 mL blood during the 3 months before the start of Screening
• Female subjects who are breastfeeding, pregnant, or planning to become pregnant during the study
• Positive serology for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV) or human immunodeficiency virus antibodies (anti-HIV)-1/2, unless the absence of an active hepatitis B/C infection is confirmed by a polymerase chain reaction (PCR) test, at Screening
• Positive urine screen of drugs of abuse (if not due to concomitant medication) or alcohol breath test at Screening and/or Day -1
• Legal incapacity or limited legal capacity

Sponsors & Collaborators

• Zealand Pharma: lead

Study Sites (3)

Fázis I-es Klinikai Farmakológiai

Budapest, 1077, Hungary

Location

Szent Imre Egyetemi Oktatókórház

Budapest, 1115, Hungary

Location

Specjalistyczne Centrum Medyczne - Prywatny Szpital

Krakow, 31-559, Poland

Location

Related Publications (1)

• Agersnap MA, Sonne K, Knudsen KM, Sulowicz W. Pharmacokinetics, Safety, and Tolerability of Glepaglutide, a Long-Acting GLP-2 Analog, in Subjects with Renal Impairment. Clin Pharmacokinet. 2023 Apr;62(4):645-651. doi: 10.1007/s40262-023-01215-9. Epub 2023 Feb 21.

  PMID: 36811175 DERIVED

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

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

Model Details: If only Part A will be conducted total subjects of 16 will be enrolled if Part B also will be conducted up to 48 subjects will be enrolled.

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: November 26, 2019
• Study Start: December 10, 2019
• Primary Completion: July 14, 2020
• Study Completion: July 14, 2020
• Last Updated: November 18, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

HU (2); PL (1)