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

NCT02859207 | Completed Phase 1

• 1 other identifier: E2609-A001-103
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

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.

Conditions

Early Alzheimer's Disease

Keywords

Early Alzheimer's disease; E2609; Mild and Moderate Hepatic Impairment

Outcome Measures

Primary Outcomes (3)

• Mean maximum plasma concentration (Cmax) of E2609

  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).

  Day 1 through 7

• Mean area under plasma concentration versus time curve from time zero to time of last quantifiable concentration (AUC(0-t)) of E2609

  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).

  Day 1 through 7

• Mean area under plasma concentration versus time curve from time zero to infinity (AUC(0-inf)) of E2609

  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).

  Day 1 through 7

Secondary Outcomes (10)

• Mean time to reach maximum plasma concentration (tmax) of E2609 and its metabolites

  Day 1 through 7

• Mean terminal phase plasma half-life (t1/2) of E2609 and its metabolites

  Day 1 through 7

• Mean apparent total body clearance (CL/F) of E2609

  Day 1 through 7

• Mean apparent volume of distribution (Vz/F) of E2609

  Day 1 through 7

• 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

Study Arms (4)

Cohort 1

EXPERIMENTAL

Participants with mild hepatic impairment (Child-Pugh class A).

Drug: E2609

Cohort 1C

EXPERIMENTAL

Healthy participants (control) matched to participants in Cohort 1.

Drug: E2609

Cohort 2

EXPERIMENTAL

Participants with moderate hepatic impairment (Child-Pugh class B)

Drug: E2609

Cohort 2C

EXPERIMENTAL

Healthy participants (control) matched to participants in Cohort 2

Drug: E2609

Interventions

E2609 DRUG

Participants will receive a single 50-mg dose (1× 50-mg E2609 tablet).

Cohort 1; Cohort 1C; Cohort 2; Cohort 2C

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Nonsmoking, male or female, ≥18 years and ≤70 years of age at the time of informed consent, and with body mass index (BMI) of up to 40 kg/m2, inclusive.
• For Cohorts 1C and 2C: healthy participants matched to participants with mild or moderate hepatic impairment with regard to age (±10 years), body weight (±20%), and gender; and as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiogram (ECG), and clinical laboratory determinations.

You may not qualify if:

• For all Participants (Cohorts 1, 2, 1C, and 2C)
• Females participants who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[ß-hCG\] test. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the dose of study drug.
• Females of childbearing potential who:
• Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method \[such as condom plus diaphragm with spermicide\], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period or for 28 days after study drug discontinuation.
• Are currently abstinent and do not agree to use a double-barrier method (as previously described) or refrain from sexual activity during the study period or for 28 days after study drug discontinuation .
• Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product except those containing estradiol for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation.
• Are using estradiol-containing hormonal contraceptives within 4 weeks before dosing (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal \[amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause\] or have been sterilized surgically \[eg, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy; all with surgery at least 1 month before dosing\]).
• Inability to tolerate oral medication.
• Inability to be venipunctured and/or tolerate venous access. For Hepatically Impaired Participants (Cohorts 1 and 2)
• Any significant acute medical illness (such as new conditions or exacerbation or pre-existing conditions) within 4 weeks before dosing.
• Medical conditions which are not adequately and stably controlled on stable doses of medications or which, in the clinical opinion of the investigator, may interfere with study procedures or participant safety within 4 weeks before dosing; eg, psychiatric disorders and disorders of the gastrointestinal tract, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism. Participants with history of seizures during adulthood are excluded. Participants with a history of Gilbert's syndrome are excluded.
• History of esophageal and gastric variceal bleeding within the past 3 months unless the participant has completed a course of endoscopic therapy with the appropriate documentation (eg, endoscopy report) of successful ablation of esophageal varices; participants with esophageal varices may be included if not bleeding within the past 3 months or have been treated adequately by ablation therapy.
• Spontaneous bacterial peritonitis within 3 months before dosing.
• Treatment with plasmapheresis within 6 months before dosing.
• Primarily cholestatic liver diseases (eg, primary biliary cirrhosis or primary sclerosing cholangitis).

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (3)

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

Minneapolis, Minnesota, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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: August 4, 2016
• First Posted: August 8, 2016
• Study Start: August 1, 2016
• Primary Completion: December 6, 2016
• Study Completion: January 25, 2017
• Last Updated: June 8, 2017

Record last verified: 2017-05

Locations

US (3)