A Study to Evaluate the Pharmacokinetics of E2609 and Its Metabolites in Subjects With Mild and Moderate Hepatic Impairment Compared With Healthy Subjects

Phase 1

Completed

• Conditions: Early Alzheimer's Disease
• Interventions: Drug: E2609

• Registration Number: NCT02859207
• Lead Sponsor: Eisai Inc.

Brief Summary

The primary objective of the study is to evaluate the effects of hepatic impairment on the pharmacokinetics (PK) of E2609 after a single dose administration.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08
• Study First Submitted: 2016-08-04
• Study First Submitted QC: 2016-08-04
• Study First Posted: 2016-08-08
• Primary Completion: 2016-12-06
• Study Completion: 2017-01-25
• Status Verified: 2017-05
• Last Update Submitted: 2017-06-07
• Last Update Posted: 2017-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	E2609	Participants with mild hepatic impairment (Child-Pugh class A).
Cohort 1C	E2609	Healthy participants (control) matched to participants in Cohort 1.
Cohort 2	E2609	Participants with moderate hepatic impairment (Child-Pugh class B)
Cohort 2C	E2609	Healthy participants (control) matched to participants in Cohort 2

Primary Outcome Measures

Name	Time	Method
Mean maximum plasma concentration (Cmax) of E2609	Day 1 through 7	Blood samples for pharmacokinetic (PK) assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Mean area under plasma concentration versus time curve from time zero to time of last quantifiable concentration (AUC(0-t)) of E2609	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Mean area under plasma concentration versus time curve from time zero to infinity (AUC(0-inf)) of E2609	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).

Secondary Outcome Measures

Name	Time	Method
Mean AUC(0-inf) values adjusted by unbound fraction in plasma (AUCu) of E2609	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Mean Cmax values adjusted for unbound fraction in plasma (Cmaxu) of E2609	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Mean time to reach maximum plasma concentration (tmax) of E2609 and its metabolites	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Mean ratio of AUC(0-inf) of individual metabolite to AUC(0-inf) of E2609, corrected for molecular weight (AUC metabolite ratio)	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Number of participants with treatment emergent adverse events and serious adverse events	Up to approximately 36 weeks
Mean apparent volume of distribution (Vz/F) of E2609	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Mean Apparent clearance relative to the unbound plasma concentration based on AUCu (CLu/F) of E2609	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Mean terminal phase plasma half-life (t1/2) of E2609 and its metabolites	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Mean apparent total body clearance (CL/F) of E2609	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).
Mean plasma protein unbound fraction (fu) of E2609	Day 1 through 7	Blood samples for PK assessments will be collected on Day 1 (before dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing), Day 2 (24 and 36 hours after dosing), Day 3 (48 hours after dosing), Day 4 (72 hours after dosing), Day 5 (96 hours after dosing), Day 6 (120 hours after dosing), and Day 7 (144 hours after dosing).