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

Completed · Phase 1

Conditions studied: Early Alzheimer's Disease

In brief

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.

Key facts

Study ID

NCT02859207

Run by

Eisai Inc.

People needed

32

Starts

2016-08-01

Expected to finish

2017-01-25

Last updated by the study team

2017-06-08

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: accepted.

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 1 and 2: stable mild or moderate hepatic impairment conforming to Child-Pugh class A or B, respectively, documented by medical history, physical examination and 1 or more of the following diagnostic procedures documented in the medical notes: liver biopsy, computed tomography (CT) scan, magnetic resonance imaging (MRI), ultrasound, radionuclide liver/spleen scan, or abdominal laparoscopy. Participants whose liver imaging was done more than 1 year ago or previous results were not available, should have a liver ultrasound scan to ensure that the liver structure is consistent with the diagnosis of hepatic impairment and that there are no exclusionary features.
• 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]).
• Males who have not had a successful vasectomy (unconfirmed azoospermia) or they and their female partners do not meet the criteria specified in exclusion criterion 2 (eg, unwilling to refrain from sexual activity, not of childbearing potential or practicing highly effective contraception throughout the study period or for 28 days after study drug discontinuation).
• 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).
• Current or recent (within 3 months before Screening) history of significant gastrointestinal disease other than that secondary to hepatic impairment.
• Autoimmune liver disease.
• Active alcoholic hepatitis determined either clinically or by histology per the discretion of the investigator.
• History of hepatoma or metastatic disease of the liver.
• Presence of severe ascites or edema.
• Presence of hepatopulmonary syndrome or hydrothorax, or hepatorenal syndrome.
• Known significant bleeding diathesis that could preclude multiple venipunctures (International Normalized Ratio [INR] >2.5).
• Any major surgery within 4 weeks before dosing.
• Any history of abdominal surgery that may affect the pharmacokinetic (PK) of E2609 (eg, hepatectomy, nephrectomy, digestive organ resection, transjugular intrahepatic portosystemic shunt [TIPS]) at Screening or Baseline (history of cholecystectomy need not be exclusionary).

Where it is running

• Study site — Miami, Florida, United States
• Study site — Orlando, Florida, United States
• Study site — Minneapolis, Minnesota, United States

Full record on ClinicalTrials.gov

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