Pharmacokinetics of Entospletinib in Adults With Normal and Impaired Liver Function

Phase 1

Completed

• Conditions: Oncology
• Interventions: Drug: Entospletinib

• Registration Number: NCT02521376
• Lead Sponsor: Gilead Sciences

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-08-10
• Study First Submitted QC: 2015-08-10
• Study First Posted: 2015-08-13
• Study Start: 2015-11-16
• Primary Completion: 2017-10-25
• Study Completion: 2017-10-25
• Status Verified: 2019-05
• Results First Submitted: 2019-05-24
• Results First Submitted QC: 2019-05-24
• Last Update Submitted: 2019-05-24
• Results First Posted: 2019-07-26
• Last Update Posted: 2019-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2 (Severe Hepatic Impairment)	Entospletinib	Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5.
Cohort 1 (Moderate Hepatic Impairment)	Entospletinib	Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5.
Cohort 3 (Mild Hepatic Impairment)	Entospletinib	Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Parameter: AUCtau of ENTO	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	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Pharmacokinetic (PK) Parameter: Cmax of ENTO	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	Cmax is defined as the maximum concentration of drug.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	Baseline up to Day 9 plus 30 days	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.
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	Baseline up to Day 9 plus 30 days	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.

Trial Locations

Locations (6)

The Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States

Auckland Clinical Studies; 🇳🇿 Auckland, New Zealand

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

DaVita Clinical Research; 🇺🇸 Minneapolis, Minnesota, United States

Clinical Pharmacology of Miami, Inc. (CPMI); 🇺🇸 Miami, Florida, United States

APEX GmBH; 🇩🇪 Munich, Germany