Study to Evaluate the Effects of Renal Impairment on the Pharmacokinetics, Safety and Tolerability of GC4419

NCT05412472 | Completed Phase 1 FDA Drug

• 1 other identifier: GTI-4419-003
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

The study is a two-center, Phase 1, open-label, single-dose, one-period, four groups, PK study in subjects with various severities of renal impairment and matched healthy controls.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (9)

• Pharmacokinetic (PK) profile for GC4419 (in plasma): AUC0-t

  Within 1 hour before the start of infusion and 0.5, 1 (immediately before the start of the IV line flushing process), 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hours after start of infusion.

• Pharmacokinetic (PK) profile for GC4419 (in plasma): AUC0-inf

  Within 1 hour before the start of infusion and 0.5, 1 (immediately before the start of the IV line flushing process), 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hours after start of infusion.

• Pharmacokinetic (PK) profile for GC4419 (in plasma): Cmax

  Within 1 hour before the start of infusion and 0.5, 1 (immediately before the start of the IV line flushing process), 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hours after start of infusion.

• Pharmacokinetic (PK) profile for GC4419 (in plasma): Residual Area

  Within 1 hour before the start of infusion and 0.5, 1 (immediately before the start of the IV line flushing process), 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hours after start of infusion.

• Pharmacokinetic (PK) profile for GC4419 (in plasma): Tmax

  Within 1 hour before the start of infusion and 0.5, 1 (immediately before the start of the IV line flushing process), 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hours after start of infusion.

• Pharmacokinetic (PK) profile for GC4419 (in plasma): T1/2el

  Within 1 hour before the start of infusion and 0.5, 1 (immediately before the start of the IV line flushing process), 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hours after start of infusion.

• Pharmacokinetic (PK) profile for GC4419 (in plasma): Kel

  Within 1 hour before the start of infusion and 0.5, 1 (immediately before the start of the IV line flushing process), 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hours after start of infusion.

• Pharmacokinetic (PK) profile for GC4419 (in plasma): CL/F

  Within 1 hour before the start of infusion and 0.5, 1 (immediately before the start of the IV line flushing process), 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hours after start of infusion.

• Pharmacokinetic (PK) profile for GC4419 (in plasma): Vd/F

  Within 1 hour before the start of infusion and 0.5, 1 (immediately before the start of the IV line flushing process), 1.5, 2, 3, 4, 6, 8, 12, 16, 24, and 36 hours after start of infusion.

Study Arms (4)

1) Healthy subjects with normal renal function

EXPERIMENTAL

Drug: GC4419

2) Mild renal impairment

EXPERIMENTAL

Drug: GC4419

3) Moderate renal impairment

EXPERIMENTAL

Drug: GC4419

4) Severe renal impairment

EXPERIMENTAL

Drug: GC4419

Interventions

GC4419 DRUG

45 mg IV infusion of GC4419 over 60 minutes.

1) Healthy subjects with normal renal function; 2) Mild renal impairment; 3) Moderate renal impairment; 4) Severe renal impairment

Eligibility Criteria

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

You may qualify if:

• Subjects must meet all of the following criteria to be included in Arm 1:
• Male or female, non-smoker ≥ 18 and ≤ 80 years of age, with BMI ≥ 18.0 and ≤ 40.0 kg/m2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females.
• Healthy as defined by the absence of clinically significant illness and surgery within 4 weeks prior to dosing; the absence of clinically significant medical history
• Females of childbearing potential partner must be willing to use an acceptable contraceptive method throughout the study and for 30 days after the study drug administration:
• Male subjects who are sexually active must be willing to use one of an acceptable contraceptive method from the first dosing until at least 90 days after the study drug administration:
• Male subjects with a pregnant partner must agree to use a condom from the first dosing until at least 90 days after the study drug administration.
• Male subjects must be willing not to donate sperm until 90 days following study drug administration. Female subjects must avoid oocyte donation until 90 days following study drug administration.
• Subjects must meet all of the following criteria to be included in Arms 2 to 4:
• Male or female, non-smoker and/or light smoker, ≥18 and ≤80 years of age, with BMI ≥ 18.0 and ≤ 40.0 kg/m2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females.
• Have a diagnosis of renal impairment that has been stable, without any significant change in overall disease status in the last 3 months
• Have an eGFR (MDRD4 equation) at screening within the range of:
• Group 2 - Mild Group: 60 - 89 mL/min/1.73 m2;
• Group 3 - Moderate Group: 30 - 59 mL/min/1.73 m2;
• Group 4 - Severe Group: \< 30 mL/min/1.73 m2 not requiring dialysis.
• The absence of clinically unstable neurological, cardiovascular, pulmonary, hematological, psychiatric, or gastrointestinal illness

You may not qualify if:

• Subjects to whom any of the following applies will be excluded from Arm 1:
• Any clinically significant abnormality at physical examination or clinically significant abnormal laboratory test results at screening.
• Positive test for hepatitis B, hepatitis C, or HIV at screening;
• History of anaphylaxis, hypersensitivity reaction, or a clinically significant reaction to any drug.
• Clinically significant ECG abnormalities or vital sign abnormalities
• History of significant alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to the screening visit
• History of significant drug abuse within one year prior to screening or use of soft drugs within 3 months prior to the screening visit or hard drugs within 1 year prior to screening
• Participation in a clinical research study within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing
• Positive urine drug screen, alcohol breath test, or urine cotinine 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 medication other than topical products without significant systemic absorption and hormonal contraceptives:
• Prescription medication within 14 days prior to dosing;
• Over-the-counter products and natural health products within 7 days prior to dosing
• A depot injection or an implant of any drug within 3 months prior to dosing.

Sponsors & Collaborators

• Galera Therapeutics, Inc.: lead

Study Sites (2)

Inventiv Health Clinical -Research Pharmacy Unit

Miami, Florida, 33136, United States

Location

University of Miami Division of Clinical Pharmacology

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

avasopasem manganese

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: June 9, 2022
• Study Start: April 4, 2019
• Primary Completion: January 30, 2021
• Study Completion: April 6, 2021
• Last Updated: June 9, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)