Pharmacokinetics of Entospletinib in Adults With Normal and Impaired Liver Function

Study Overview
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Brief Summary
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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.

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

Conditions
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Oncology

Intervention / Treatment
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* Drug: Entospletinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |