A Study to Evaluate the Effects of Renal Impairment on the Pharmacokinetics of ELX-02

NCT03776539 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: EL-008
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

Phase 1 - Pharmacokinetics in Patients with Impaired Renal Function

Conditions

Impaired Renal Function

Keywords

Impaired Renal Function; PK

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetic Parameters- Plasma AUC0-24

  Area under the curve (AUC0-24) of ELX-02 plasma concentration following a single subcutaneous (SC) dose

  0.25, 0.5, 0.75, 1, 2, 4, 6, 12, and 24 hours after dosing

• Pharmacokinetic Parameters- Plasma Cmax

  Peak Plasma Concentration (Cmax) of ELX-02 following a single subcutaneous (SC) dose in subjects with normal renal function, mild, moderate, or severe renal impairment

  0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 36, 48, 72, and 168 (Day 8) hours after dosing

• AUC0-inf

  Area under the curve (AUC0-inf) of ELX-02 plasma concentration following a single subcutaneous (SC) dose

  0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 36, 48, 72, and 168 (Day 8) hours after dosing

• Pharmacokinetic Parameters - Plasma Tmax

  Time to maximum concentration (Tmax) of ELX-02 plasma concentration following a single subcutaneous (SC) dose

  0.25, 0.5, 0.75, 1, 2, 4, 6, 12, and 24 hours after dosing.

• Urine Pharmacokinetics Parameter - Ae0-t

  Cumulative amount of unchanged drug excreted into urine (Ae0-t) of ELX-02 following a single subcutaneous (SC) dose

  Pre-dose (first void in the morning of Day 1), 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36, 36-48, and 48-72 hours post-dose

• Urine Pharmacokinetic Parameter - Rmax

  Maximum rate of urinary extraction (Rmax) of ELX-02 following a single subcutaneous (SC) dose

  Pre-dose (first void in the morning of Day 1), 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36, 36-48, and 48-72 hours post-dose

• Number of Patients Reporting Treatment-Emergent Adverse Events (TEAEs) [Safety]

  TEAEs are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the study treatment

  1-8 days

Study Arms (1)

ELX-02

EXPERIMENTAL

Drug: ELX-02

Drug: ELX-02

Interventions

ELX-02 DRUG

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.

ELX-02

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, non-smoker and/or light smoker
• 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.
• 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:
• Group 1 - Mild Group: 60 - 89 mL/min/1.73 m2;
• Group 2 - Moderate Group: 30 - 59 mL/min/1.73 m2;
• 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.
• 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.
• 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.
• Other than renal impairment, have no other conditions which may significantly impact study drug absorption or metabolism.
• 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.
• 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.
• 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.
• 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.
• Male subjects must be willing not to donate sperm until 90 days following study drug administration.
• Able to understand and willing to sign the Informed Consent Form (ICF) and comply with the study restrictions.

You may not qualify if:

• 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.
• Has a functioning renal transplant.
• Major illness or surgery within 4 weeks prior to dosing.
• 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.
• Positive test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at screening.
• History of allergic reactions, hypersensitivity or toxic reactions to aminoglycosides.
• History of anaphylaxis.
• Supine 12-lead ECG abnormalities at screening considered clinically significant.
• Clinically significant vital sign abnormalities at screening.
• History of significant drug or alcohol abuse within six months prior to screening.
• 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.
• Positive urine drug screen or alcohol test at screening.
• Female subject with positive pregnancy test at screening.
• Breast-feeding or pregnant subject within 6 months prior to study drug administration.
• Use of any drugs known as strong inducer or inhibitor of hepatic drug metabolism within 30 days prior to study drug administration.

Sponsors & Collaborators

• Eloxx Pharmaceuticals, Inc.: lead
• Syneos Health: collaborator

Study Sites (2)

Inventiv Health Clinical -Research Pharmacy Unit

Miami, Florida, 33136, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Related Links

• Description Eloxx Pharmaceuticals Website

MeSH Terms

Conditions

Renal Insufficiency

Interventions

ELX-02

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Executive Director Clinical Trials
• Organization: Eloxx Pharmaceuticals

CTI@eloxxpharma.com

1-781-577-5300

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: December 4, 2018
• First Posted: December 14, 2018
• Study Start: January 4, 2019
• Primary Completion: July 30, 2019
• Study Completion: August 7, 2019
• Last Updated: April 13, 2021
• Results First Posted: April 13, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)