Clinical trial NCT04178447: Pharmacokinetic Profile of Glepaglutide After a Single Injection in Subjects With Varying Degrees of Renal Function
Official title: An Open-label, Multi-center Trial to Evaluate the Pharmacokinetic Profile of Glepaglutide After a Single Subcutaneous Injection in Subjects With Varying Degrees of Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
First posted: 2019-11-26
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: OTHER

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.


Eligibility criteria: 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 -

Primary outcomes:
measure: Pharmacokinetic Variables
timeFrame: 11 days
Secondary outcomes:
measure: Safety Variables
timeFrame: 11 days
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Fázis I-es Klinikai Farmakológiai
city: Budapest
country: Hungary
facility: Szent Imre Egyetemi Oktatókórház
city: Kraków
country: Poland
facility: Specjalistyczne Centrum Medyczne - Prywatny Szpital
Study officials:
References: