Study of Pharmacokinetics and Safety of Apraglutide in Participants With Normal and Impaired Kidney Function.
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Intervention: Apraglutide
Intervention description: Single dose of apraglutide 5 mg.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Renal Function; Renal Impairment; Kidney Function

Summary:

      Study of pharmacokinetics and safety of apraglutide in participants with normal and impaired
      kidney function.
    

Eligibility criteria:

        Inclusion Criteria:

        All Participants

          -  Age between 18 and 75 years inclusive

          -  Subjects who are willing and able to comply with the study procedures

          -  Subjects able to understand and willing to sign the informed consent

          -  Body mass index (BMI) of ≥17.5 to ≤40 kg/m2; and a total body weight of >50 kg (110
             lb).

          -  Women of childbearing potential (WOCBP) on highly effective method of contraception
             during the trial and for 1 month after the end of trial (EOT) visit. Sterilized or
             infertile or postmenopausal females.

          -  Male subjects with a female partner of childbearing potential: highly effective
             methods of contraception and no sperm donation during the trial and for 1 month after
             (EOT) visit.

        Healthy participants

          -  No clinically relevant abnormalities (medical history, vital signs, ECG, safety labs)

          -  eGFR measured by CKD-EPI ≥90 mL/min/1.73 m2) at two screening visits

          -  Demographically comparable to the group of subjects with impaired renal function:

        Participants with impaired renal function

          -  Severe renal impairment: eGFR <30 mL/min/1.73 m2, but not requiring hemodialysis

          -  Moderate renal impairment: eGFR ≥30 mL/min/1.73 m2 and <60 mL/min/1.73 m2

          -  Mild renal impairment: eGFR ≥60 and <90 mL/min/1.73 m2

        Exclusion Criteria:

        All Subjects

          -  Renal transplant recipients

          -  History of systemic infection

          -  Any active malignancies or history of malignancies within the past 2 years

          -  Acute or chronic medical or psychiatric condition

          -  Treatment with an IMP within 30 days or 5 half-lives (whichever is longer) preceding
             the dose of IMP

          -  Male subjects partners of WOCBP who are unable to comply with the contraceptive
             measures

          -  History of clinically significant intestinal adhesions and/or chronic abdominal pain

          -  History of known colon polyps or family history of familial adenomatous polyposis

          -  Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or human
             immunodeficiency virus (HIV)-1 and -2 antibodies

          -  Serum albumin concentration <25 g/L (2.5 g/dL)

          -  Hemoglobin concentration <90 g/L (9.0 g/dL)

          -  Aspartate amino transaminase (AST) or alanine amino transaminase (ALT) values >2 ×
             upper limit of normal (ULN)

          -  Proteinuria of >3 g total bilirubin >1.5 × ULN

          -  Positive urine test for alcohol or illicit drugs at either Screening or admission.

          -  Clinically significant abnormalities on 12-lead ECG

          -  Use of prescription or non-prescription drugs and dietary supplements within 7 days or
             five half-lives (whichever is longer) prior to Day 1. Stable concomitant medications
             may be given to subjects with renal impairment, if they are considered necessary for
             the welfare of the subjects.

          -  History of regular alcohol consumption exceeding seven drinks/week for females or 14
             drinks/week for males (1 drink = 5 ounces [150 mL] of wine, or 12 ounces [360 mL] of
             beer, or 1.5 ounces [45 mL] of hard liquor) within 3 months of Screening

          -  Female subjects of childbearing potential who are unwilling or unable to use highly
             effective methods of contraception for the duration of the trial and for at least 1
             month after the administration of the IMP; pregnant female subjects; female subjects
             planning to become pregnant during the duration of the trial and until 1 month after
             the administration of the IMP; breastfeeding female subjects

          -  Blood donation of approximately 500 mL or more within 60 days prior to the dose of
             IMP. Plasma donations of approximately 500 mL or more within 28 days prior to the dose
             of IMP

        Additional Exclusion Criteria for Healthy Subjects with Normal Renal Function

          -  Evidence or history of clinically significant abnormalities

          -  Evidence or history of clinically significant dermatological condition

        Additional Exclusion Criteria for Subjects with Impaired Renal Function

          -  Subjects requiring hemodialysis and/or peritoneal dialysis

          -  Subjects with other clinically significant disease

          -  Subjects with any significant hepatic, cardiac, or pulmonary disease or subjects who
             are clinically nephrotic. Hypertension, diabetes mellitus, hyperparathyroidism,
             ischemic heart disease are not cause for exclusion as long as the subject is medically
             stable and any drugs that are administered for these conditions are not expected to
             interfere with the PK of apraglutide.

          -  Screening BP ≥180 mmHg (systolic) or ≥110 mmHg (diastolic)