Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Mild and Moderate Hepatic Impairment Compared to Healthy Subjects

NCT ID: NCT03440424

Last Updated: 2020-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-26
• Study Completion Date: 2018-04-23

Brief Summary

This study will be conducted to assess the effect of mild and moderate hepatic impairment on the pharmacokinetics (PK) of lemborexant after a single-dose administration.

Conditions

Hepatic Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: Mild Hepatic Impairment (Child Pugh Class A)

Participants with mild hepatic impairment will receive a single 10 milligram (mg) dose (1 × 10 mg lemborexant \[E2006\] tablet) in the morning with 240 milliliters (mL) of water following an overnight fast of at least 10 hours.

Group Type: EXPERIMENTAL

Lemborexant

Intervention Type: DRUG

oral tablet

Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)

Participants with moderate hepatic impairment will receive a single 10 mg dose (1 × 10 mg lemborexant \[E2006\] tablet) in the morning with 240 mL of water following an overnight fast of at least 10 hours.

Group Type: EXPERIMENTAL

Lemborexant

Intervention Type: DRUG

oral tablet

Cohort C: Healthy Participants (Control)

Healthy participants matched to participants with hepatic impairment in Cohorts A and B (matched with regards to age, sex, body mass index \[BMI\]) will receive a single 10 mg dose (1 × 10 mg lemborexant \[E2006\] tablet) in the morning with 240 mL of water following an overnight fast of at least 10 hours.

Group Type: EXPERIMENTAL

Lemborexant

Intervention Type: DRUG

oral tablet

Interventions

Lemborexant

oral tablet

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female participants, ages 18 to 79, inclusive, at the time of informed consent
• Body Mass Index (BMI) between 18 and 40 kilograms per meters squared, inclusive, at Screening
• Voluntary agreement to provide written informed consent, and the willingness and ability to comply with all aspects of the protocol
• Nonsmokers or smokers who smoke 20 cigarettes or less per day
• For Cohorts A and B: stable (without any change in disease status for at least 60 days prior to study Screening) hepatic impairment conforming to Child-Pugh classification A or B, respectively, and documented by medical history and a physical examination
• For Cohort C: healthy participants matched to participants with hepatic impairment with regard to age (±10 years), sex, and BMI (±20%), and as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiogram (ECG), and clinical laboratory determinations

Exclusion Criteria

• Females who are breastfeeding or pregnant at Screening or Baseline
• Females of childbearing potential who did not use a highly effective method of contraception within 28 days before study entry, or who did not agree to use an approved method of contraception from 28 days before study entry, throughout the entire study period, and for 28 days after study drug discontinuation. Approved (highly effective) methods of contraception for this study included at least one of the following: 1. Total abstinence (if it was their preferred and usual lifestyle); 2. An intrauterine device or intrauterine hormone-releasing system (IUS); 3. A double-barrier method of contraception such as condom plus diaphragm with spermicide; 4. A contraceptive implant; 5. An oral contraceptive (with additional barrier method). Participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing, throughout the study, and for 28 days after study drug discontinuation; 6. Have a vasectomized partner with confirmed azoospermia. (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 (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
• Known to be positive for human immunodeficiency virus
• Currently enrolled in another clinical study or used any investigational drug or device within 4 weeks, or 5 times the half-life of the investigational drug (whichever is longer), preceding informed consent
• Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing until study discharge
• Intake of herbal preparations containing St. John's Wort within 4 weeks prior to dosing until study discharge
• Intake of nutritional supplements (including herbal preparations), foods or beverages that may affect cytochrome P3A enzyme (e.g., alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard] and charbroiled meats) within 1 week before dosing until study discharge
• Intake of beverages, food, or other products that contain caffeine from 24 hours before until 48 hours after dosing with lemborexant
• Engagement in strenuous exercise (e.g., moving large bulky items, bodybuilding) within 2 weeks prior to check-in until study discharge
• History of clinically significant drug or food allergies, or is presently experiencing significant seasonal allergies
• A prolonged QT/corrected QT (QTc) interval (QTc >480 milliseconds) demonstrated on ECG at Screening or Baseline (Day -1)
• Any major surgery within 4 weeks of study drug administration
• Any history of abdominal surgery that may affect pharmacokinetics of lemborexant (e.g., hepatectomy, nephrectomy, digestive organ resection)
• Inability to tolerate oral medication
• Inability to tolerate venous access and/or venipuncture
• Unwilling to abide by the study requirements, or in the opinion of the investigator, is not likely to complete the study

• Any significant acute medical illness (such as new conditions or exacerbation of pre-existing conditions) within 8 weeks of dosing
• Medical conditions which are not adequately and stably controlled on stable doses of medications or which, in the clinical opinion of the Principal Investigator, may interfere with study procedures or participant safety within 4 weeks before dosing (e.g., 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)
• History of esophageal and gastric variceal bleeding within the past 6 months unless the participant has completed a course of endoscopic therapy with the appropriate documentation (e.g., endoscopy report) of successful ablation of esophageal varices; participants with esophageal varices may be included if not bleeding within the past 6 months or have been treated adequately by ablation therapy, as specified above.
• Spontaneous bacterial peritonitis within 3 months of dosing
• Treatment with plasmapheresis within 6 months of dosing
• Primarily cholestatic liver diseases (e.g., primary biliary cirrhosis or primary sclerosing cholangitis)
• Current or recent (within 3 months prior to 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
• 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 normalization ratio >2.5)
• Creatinine clearance <60 milliliters per minute at Screening or Baseline as calculated using Cockroft and Gault Equation
• The participant's standard therapy/concomitant medication for diseases related to cirrhosis has not remained stable/unchanged for at least 14 days before the first dose of study drug
• History of drug or alcohol dependency or abuse within 4 weeks prior to Screening, or those who have a positive urine drug test or breath alcohol test at Screening or Baseline unless a prescribed medication for the underlying condition is the cause of the positive urine screen

• Presence of active liver disease, or acute liver injury, as indicated by (1) an abnormal liver function test, or (2) clinical or laboratory signs of active viral hepatitis (including B and C, as demonstrated by positive serology at Screening)
• Clinically significant illness, within 4 weeks prior to dosing, that requires medical treatment or may influence the outcome of the study; e.g., psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism
• Any abnormal finding based on physical examination, assessment of vital signs, ECG, or laboratory test results that require treatment or clinical follow-up based on the investigator's opinion
• History of drug or alcohol use disorder within the 2 years prior to Screening, or those who have a positive urine drug test or breathalyzer alcohol test at Screening or Baseline
• Use of any prescription drugs within 4 weeks prior to dosing until study discharge
• Intake of any over-the-counter medications within 2 weeks prior to dosing until study discharge

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Purdue Pharma LP

INDUSTRY

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Pharmacology of Miami, LLC

Miami, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

E2006-A001-104

Identifier Type: -

Identifier Source: org_study_id