Study to Evaluate the Pharmacokinetics of Selonsertib in Participants With Normal and Impaired Hepatic Function

NCT02509624 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GS-US-223-10182015-002444-14
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objective of this study is to evaluate the pharmacokinetics (PK) of selonsertib in participants with impaired hepatic function relative to matched, healthy controls.

Conditions

Diabetic Kidney Disease

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic (PK) Parameter: AUCinf of Selonsertib and Its Metabolite GS-607509

  AUCinf is defined as the concentration of drug extrapolated to infinite time.

  0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample.

• PK Parameter: AUClast of Selonsertib and Its Metabolite GS-607509

  AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample.

• PK Parameter: Cmax of Selonsertib and Its Metabolite GS-607509

  Cmax is defined as the maximum concentration of drug.

  0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample.

Secondary Outcomes (2)

• Percentage of Participants Experiencing Treatment-Emergent Study Drug-related Adverse Events (AEs)

  Day 1 plus 30 days

• Percentage of Participants Experiencing Any Treatment-Emergent and Grade ≥ 3 Laboratory Abnormalities

  Day 1 plus 30 days

Study Arms (3)

Moderate hepatic impairment (Cohort 1)

EXPERIMENTAL

Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1.

Drug: Selonsertib

Severe hepatic impairment (Cohort 2)

EXPERIMENTAL

Participants with severe hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1.

Drug: Selonsertib

Mild hepatic impairment (Cohort 3)

EXPERIMENTAL

Participants with mild hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1.

Drug: Selonsertib

Interventions

Selonsertib DRUG

6 mg tablets administered orally in fed state

Also known as: GS-4997

Mild hepatic impairment (Cohort 3); Moderate hepatic impairment (Cohort 1); Severe hepatic impairment (Cohort 2)

Eligibility Criteria

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

You may qualify if:

• All participants:
• Body mass index (BMI) from 18 to 40 kg/m\^2, inclusive at study screening
• Creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening
• Participants with impaired hepatic function:
• Aside from hepatic insufficiency, participants must be sufficiently healthy for study participation based upon screening evaluations.
• Must have diagnosis of chronic (\> 6 months), stable hepatic impairment with no clinically significant change in hepatic status within the 3 months (90 days) prior to study drug administration (Day 1).
• Participants with severe hepatic impairment must have a score on the Child-Pugh-Turcotte scale of 10-15 at screening.
• Participants with moderate hepatic impairment must have a score on the Child-Pugh-Turcotte scale of 7-9 at screening.
• Participants with mild hepatic impairment must have a score on the Child-Pugh-Turcotte scale of 5-6 at screening.
• Healthy participants (matched control):
• Must be in good health based upon screening evaluations.

You may not qualify if:

• All participants:
• Pregnant or lactating females
• Have received any investigational compound or device within 30 days prior to study dosing
• Current alcohol or substance abuse
• A positive test result for human immunodeficiency virus (HIV-1/2) antibody
• Have poor venous access that limits phlebotomy
• Significant serious skin disease, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria
• Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)
• Unstable cardiac disease, including history of myocardial infarction within 1 year of screening, recurrent episodes of ventricular tachycardia despite appropriate medical therapy, decompensated congestive heart failure, or dilated cardiomyopathy with left ventricular ejection fraction \< 40%, or a family history of Long QT Syndrome, or unexplained death in an otherwise healthy participants between the ages of 1 and 30 years.
• Syncope, palpitations, or unexplained dizziness
• Implanted defibrillator or pacemaker
• Severe peptic ulcer disease, severe gastroesophageal reflux disease, or other severe gastric acid hypersecretory conditions
• History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
• Currently registered on an organ transplantation list.
• History of bleeding from esophageal varices within 90 days prior to Admission (Day -1).

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (5)

Unknown Facility

Denver, Colorado, United States

Location

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

Minneapolis, Minnesota, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

selonsertib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: July 16, 2015
• First Posted: July 28, 2015
• Study Start: August 18, 2015
• Primary Completion: December 15, 2015
• Study Completion: December 15, 2015
• Last Updated: January 27, 2021
• Results First Posted: January 27, 2021

Record last verified: 2021-01

Locations

US (5)