A Study to Evaluate the Effects of Renal Impairment on the Pharmacokinetics of ELX-02
Condition: Impaired Renal Function
MeSH terms: Renal Insufficiency
Intervention: ELX-02
Intervention description: ELX-02 is a synthetic, designer eukaryotic ribosomal specific glycoside (ERSG) optimized as a translational read-through drug. All groups will get the same treatment.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Subjects will be categorized in 4 groups:
Group 1: subjects with mild renal impairment
Group 2: subjects with moderate renal impairment
Group 3: subjects with severe renal impairment
Group 4 (control group): subjects with normal renal function
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Impaired Renal Function; PK

Summary:

      Phase 1 - Pharmacokinetics in Patients with Impaired Renal Function
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, non-smoker and/or light smoker

          2. Have a diagnosis of renal impairment that has been stable, without any significant
             change in overall disease status in the last 3 months prior to screening.

          3. Have an estimated glomerular filtration rate (eGFR) expressed in mL/min/1.73 m2
             (Modification of Diet in Renal Disease 4-variable [MDRD4] equation) at screening
             within the range of:

               1. Group 1 - Mild Group: 60 - 89 mL/min/1.73 m2;

               2. Group 2 - Moderate Group: 30 - 59 mL/min/1.73 m2;

               3. Group 3 - Severe Group: < 30 mL/min/1.73 m2 not requiring dialysis. eGFR results
                  that are deemed inconsistent with the usual stage of renal impairment may be
                  repeated. Subjects are categorized into severity group at screening. If the eGFR
                  scores change on Day-1 or other visit due to a non-clinically significant change
                  in clinical status or laboratory result, the subject keeps the original severity
                  group.

          4. Subject may have stable treated medical illnesses and underlying diseases producing
             the renal impairment such as diabetes, hypertension, or cardiovascular disease,
             providing that, in the opinion of the PI, the disease is stable.

          5. Have normal or non-clinically significant findings at physical examination, vital
             signs and electrocardiogram (ECG) and normal limits or non-clinically significant
             deviations in clinical laboratory evaluations at screening.

          6. Other than renal impairment, have no other conditions which may significantly impact
             study drug absorption or metabolism.

          7. Stable medical regimen, deemed not to interact with study drug PK, for 14 days prior
             to dosing, except for routine daily management of electrolytes (e.g. potassium),
             acid-base, or other associated disorders expected in patients with renal impairment.

          8. Females of childbearing potential who are sexually active with a non-sterile male
             partner (sterile male partners are defined as men vasectomized since at least 6
             months) must be willing to use acceptable contraceptive method throughout the study
             and for 30 days after study drug administration.

          9. Male subjects who are not vasectomized for at least 6 months, and who are sexually
             active with a non-sterile female partner (sterile female partners include
             post-menopausal females and surgically sterile females) must be willing to use
             acceptable contraceptive method from dosing until at least 90 days after study drug
             administration.

         10. Male subjects (including men who have had vasectomy) with a pregnant partner must
             agree to use a condom from dosing until at least 90 days after study drug
             administration.

         11. Male subjects must be willing not to donate sperm until 90 days following study drug
             administration.

         12. Able to understand and willing to sign the Informed Consent Form (ICF) and comply with
             the study restrictions.

        Exclusion Criteria:

          1. Unstable renal function or acute exacerbation of renal disease within 14 days of study
             drug administration, as indicated by recent history or worsening of clinical and/or
             laboratory signs of renal impairment.

          2. Has a functioning renal transplant.

          3. Major illness or surgery within 4 weeks prior to dosing.

          4. Clinically significant unstable medical condition or history of any illness that may
             increase the risk associated with study participation or investigational drug
             administration or may interfere with the interpretation of study results and would
             make the subject inappropriate for entry into this study.

          5. Positive test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at
             screening.

          6. History of allergic reactions, hypersensitivity or toxic reactions to aminoglycosides.

          7. History of anaphylaxis.

          8. Supine 12-lead ECG abnormalities at screening considered clinically significant.

          9. Clinically significant vital sign abnormalities at screening.

         10. History of significant drug or alcohol abuse within six months prior to screening.

         11. Participation in a clinical research study involving the administration of an
             investigational or marketed drug or device within 30 days (or 5 half-lives, whichever
             is longer) prior to dosing, administration of a biological product in the context of a
             clinical research study within 90 days prior to dosing, or concomitant participation
             in an investigational study involving no drug or device administration.

         12. Positive urine drug screen or alcohol test at screening.

         13. Female subject with positive pregnancy test at screening.

         14. Breast-feeding or pregnant subject within 6 months prior to study drug administration.

         15. Use of any drugs known as strong inducer or inhibitor of hepatic drug metabolism
             within 30 days prior to study drug administration.

         16. Use of medication other than stable medications approved by the PI and topical
             products without significant systemic absorption.

         17. Use of prohibited medications as directed in the protocol.

         18. Donation of plasma within 7 days prior to dosing. Donation or loss of blood within 30
             days prior to the first dosing.

         19. Any reason which, in the opinion of the PI, would prevent the subject from
             participating in the study.

         20. Inability to be venipunctured and/or tolerate catheter venous access.

         21. Presence of mitochondrial mutation(s) making the subject susceptible to aminoglycoside
             toxicity.

         22. Presence of signs of dehydration, recent history of neuromuscular blockade or
             clinically significant history of vestibular impairment.