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

Phase 1

Completed

• Conditions: Renal Impairment
• Interventions: Drug: Glepaglutide

• Registration Number: NCT04178447
• Lead Sponsor: Zealand Pharma

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-11-25
• Study First Submitted QC: 2019-11-25
• Study First Posted: 2019-11-26
• Study Start: 2019-12-10
• Status Verified: 2020-03
• Primary Completion: 2020-07-14
• Study Completion: 2020-07-14
• Last Update Submitted: 2020-11-17
• Last Update Posted: 2020-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• All subjects

  1. Able to understand and willing to sign the informed consent

  2. eGFR values as defined in in the arms

  3. Willing and able to comply with the study requirements

  4. Male and female subjects age 18 to 70 years (both inclusive) at the time of informed consent

  5. BMI 20.0 - 30.0 kg/m2 both inclusive

  6. Must be willing to comply with the contraception, sperm-donation requirements, and study restrictions.

     Renally Impaired Subjects (in Addition)

  7. 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.

Exclusion Criteria

All Subjects

1. Suspicion of hypersensitivity, intolerance, or allergy to glepaglutide

2. History of alcohol or drug abuse

3. 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

4. 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)

5. Acute illness within 14 days prior to dosing unless mild in severity and approved by the Investigator and Sponsor's medical representative

6. 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

7. 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

8. 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

9. Previous exposure to glepaglutide

10. Donation or loss of more than 450 mL blood during the 3 months before the start of Screening

11. Female subjects who are breastfeeding, pregnant, or planning to become pregnant during the study

12. 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

13. Positive urine screen of drugs of abuse (if not due to concomitant medication) or alcohol breath test at Screening and/or Day -1

14. Legal incapacity or limited legal capacity

    Renally Impaired Subjects (in Addition)

15. Acute renal failure (as judged by the Investigator)

16. Renal impairment requiring dialysis

17. History of kidney transplant regardless of functionality

18. Serum albumin concentration <25 g/L

19. Haemoglobin concentration <100 g/L

20. Medications known to affect the elimination of serum creatinine (e.g., trimethoprim or cimetidine) and competitors of renal tubular secretion (e.g., probenecid) within 60 days prior to study drug administration

    Subjects With Normal Renal Function (in Addition)

21. Significant medical history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2: normal renal function	Glepaglutide	subjects with eGFR ≥90 mL/min/1.73 m2
Group 1: ESRD subjects not on dialysis or severe RI	Glepaglutide	subjects with eGFR \<15 mL/min/1.73 m2) or (eGFR 15 to \<30 mL/min/1.73 m2)
Group 4: mild RI	Glepaglutide	subjects with eGFR 60 to \<90 mL/min/1.73 m2
Group 3: moderate RI	Glepaglutide	subjects with eGFR 30 to \<60 mL/min/1.73 m2

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Variables	11 days	AUC0-168 area under the concentration-time curve (AUC) from time 0 to 168 hours; Cmax maximum observed plasma concentration

Secondary Outcome Measures

Name	Time	Method
Safety Variables	11 days	Number of subject with AE/SAE as a measure of safety and tolerability

Trial Locations

Locations (3)

Fázis I-es Klinikai Farmakológiai; 🇭🇺 Budapest, Hungary

Szent Imre Egyetemi Oktatókórház; 🇭🇺 Budapest, Hungary

Specjalistyczne Centrum Medyczne - Prywatny Szpital; 🇵🇱 Kraków, Poland