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

NCT03440424 | Completed Phase 1 Results FDA Drug

• 1 other identifier: E2006-A001-104
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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

Keywords

mild hepatic impairment; moderate hepatic impairment; lemborexant; healthy participants; metabolites; E2006; pharmacokinetics

Outcome Measures

Primary Outcomes (5)

• Cmax: Maximum Plasma Concentration of Lemborexant

  Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Plasma pharmacokinetic (PK) data were analyzed using a non-compartmental method of analysis.

  Day 1: Predose, 0.5 up to 312 hours postdose

• AUC(0-8 Hours): Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Postdose of Lemoborexant

  Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-8 hours) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.

  Day 1: Predose, 0.5 up to 312 hours postdose

• AUC(0-72 Hours): Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Postdose of Lemoborexant

  Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-72 hours) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.

  Day 1: Predose, 0.5 up to 312 hours postdose

• AUC(0-t Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration of Lemborexant

  Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-t hours) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.

  Day 1: Predose, 0.5 up to 312 hours postdose

• AUC(0-inf): Area Under Plasma Concentration Versus Time Curve From Time Zero to Infinity of Lemborexant

  Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-inf) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.

  Day 1: Predose, 0.5 up to 312 hours postdose

Secondary Outcomes (13)

• AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Lemborexant

  Day 1: Predose, 0.5 up to 312 hours postdose

• Cmax: Maximum Plasma Concentration of Lemborexant's Metabolites M4, M9, and M10

  Day 1: Predose, 0.5 up to 312 hours postdose

• Tmax: Time to Reach Maximum Plasma Concentration of Lemborexant and Its Metabolites M4, M9, M10

  Day 1: Predose, 0.5 up to 312 hours postdose

• AUC(0-8 Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to 8 Hours Postdose of Lemborexant's Metabolites M4, M9, and M10

  Day 1: Predose, 0.5 up to 312 hours postdose

• AUC(0-72 Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to 72 Hours Postdose of Lemborexant's Metabolites M4, M9, and M10

  Day 1: Predose, 0.5 up to 312 hours postdose

Study Arms (3)

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

EXPERIMENTAL

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.

Drug: Lemborexant

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

EXPERIMENTAL

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.

Drug: Lemborexant

Cohort C: Healthy Participants (Control)

EXPERIMENTAL

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.

Drug: Lemborexant

Interventions

Lemborexant DRUG

oral tablet

Cohort A: Mild Hepatic Impairment (Child Pugh Class A); Cohort B: Moderate Hepatic Impairment (Child Pugh Class B); Cohort C: Healthy Participants (Control)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Inc.: lead
• Purdue Pharma LP: collaborator

Study Sites (2)

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Interventions

lemborexant

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

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: February 14, 2018
• First Posted: February 22, 2018
• Study Start: January 26, 2018
• Primary Completion: April 23, 2018
• Study Completion: April 23, 2018
• Last Updated: March 20, 2020
• Results First Posted: January 18, 2020

Record last verified: 2018-02

Locations

US (2)