Pharmacokinetics of Entospletinib in Adults With Normal and Impaired Liver Function

A Phase 1, Open-Label, Multiple Dose Study to Evaluate the Pharmacokinetics of Entospletinib in Subjects With Normal and Impaired Hepatic Function

The primary objective of this study is to evaluate the pharmacokinetics of entospletinib (ENTO) and/or its metabolites (if applicable) in participants with impaired hepatic function (stratified by smoking status, as appropriate) relative to matched, healthy controls.

Study Overview

• Status: Completed
• Conditions: Oncology
• Intervention / Treatment: Drug: Entospletinib

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany
    • APEX GmbH
• New Zealand
  • Auckland, New Zealand
    • Auckland Clinical Studies
• United States
  • Florida
    • Miami, Florida, United States
      • Clinical Pharmacology of Miami, Inc. (CPMI)
    • Orlando, Florida, United States
      • Orlando Clinical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States
      • DaVita Clinical Research
  • Texas
    • San Antonio, Texas, United States
      • The Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Calculated body mass index from 18 to 40 kg/m^2
• Not pregnant
• Normal electrocardiogram
• Participants with impaired liver function must be sufficiently healthy based upon medical history and physical examination, vital signs, and screening laboratory evaluations.

Key Exclusion Criteria:

• Participation in another clinical study (current or within last 30 days)
• HIV, hepatitis B virus, or active hepatitis C virus infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Moderate Hepatic Impairment); Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5.	Drug: Entospletinib; Entospletinib 100 mg tablet administered orally; Other Names: GS-9973
Experimental: Cohort 2 (Severe Hepatic Impairment); Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5.	Drug: Entospletinib; Entospletinib 100 mg tablet administered orally; Other Names: GS-9973
Experimental: Cohort 3 (Mild Hepatic Impairment); Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5.	Drug: Entospletinib; Entospletinib 100 mg tablet administered orally; Other Names: GS-9973

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter: AUCtau of ENTO	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5
Pharmacokinetic (PK) Parameter: Cmax of ENTO	Cmax is defined as the maximum concentration of drug.	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	TEAEs are defined as events that meet one of the following criteria: Any adverse events (AEs) with onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or; Any AEs leading to premature discontinuation of study drug.	Baseline up to Day 9 plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each subject.	Baseline up to Day 9 plus 30 days

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2015
• Primary Completion (Actual): October 25, 2017
• Study Completion (Actual): October 25, 2017

Study Registration Dates

• First Submitted: August 10, 2015
• First Submitted That Met QC Criteria: August 10, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Actual): July 26, 2019
• Last Update Submitted That Met QC Criteria: May 24, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GS-US-339-1631; 2016-003266-98 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No