Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Normal Renal Function or With Severe Renal Impairment

NCT03443063 | Completed Phase 1 Results FDA Drug

• 1 other identifier: E2006-A001-105
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This study will be conducted to assess the effect of severe renal impairment on the pharmacokinetics of lemborexant after a single-dose administration.

Conditions

Renal Impairment

Keywords

severe renal impairment; lemborexant; normal renal function; healthy participants; metabolites; E2006; pharmacokinetics

Outcome Measures

Primary Outcomes (4)

• Maximum Observed Plasma Concentration (Cmax) of Lemborexant

  Day 1: predose, 0.5 up to 240 hours postdose

• Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Post Dose (AUC[0-72h]) of Lemborexant

  Day 1: predose, 0.5 up to 72 hours postdose

• Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of Lemborexant

  Day 1: predose, 0.5 up to 240 hours postdose

• Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Lemborexant

  Day 1: predose, 0.5 up to 240 hours postdose

Secondary Outcomes (19)

• Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10)

  Day 1: predose, 0.5 up to 240 hours postdose

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

  Day 1: predose, 0.5 up to 240 hours postdose

• Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose (AUC[0-8h]) of Lemborexant and Its Metabolites (M4, M9, and M10)

  Day 1: predose, 0.5 up to 8 hours postdose

• Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Post Dose (AUC[0-72h]) of Metabolites of Lemborexant (M4, M9, and M10)

  Day 1: predose, 0.5 up to 72 hours postdose

• Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of Metabolites of Lemborexant (M4, M9, and M10)

  Day 1: predose, 0.5 up to 240 hours postdose

Study Arms (2)

Group 1: Severe Renal Impairment

EXPERIMENTAL

Participants with severe renal impairment (estimated glomerular filtration rate \[eGFR\] 15 to 29 milliliters per minute (mL/min/1.73 square meter \[m\^2\]) and not on dialysis) will receive a single dose of 10 milligrams (mg) lemborexant (oral tablet) in the morning after an overnight fast.

Drug: Lemborexant

Group 2: Normal Renal Function

EXPERIMENTAL

Participants with normal renal function (eGFR ≥90 mL/min/1.73 m\^2) demographically matched to participants in Group 1 will receive a single dose of 10 mg lemborexant (oral tablet) in the morning after an overnight fast.

Drug: Lemborexant

Interventions

Lemborexant DRUG

oral tablet

Also known as: E2006

Group 1: Severe Renal Impairment; Group 2: Normal Renal Function

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 years, inclusive, at the time of informed consent.
• Body Mass Index between 18 and 40 kilograms per meters squared (kg/m\^2), 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.
• Participants with normal liver function.
• Estimated glomerular filtration rate (eGFR) is ≥ 90 mL/min/1.73 m\^2, as determined by the Modification of Diet in Renal Disease (MDRD) formula.
• \- Diagnosis of severe renal impairment (eGFR is 15 to 29 mL/min/1.73 m\^2, as determined by the MDRD formula) that has been stable (without any change in disease status) for 60 days prior to study Screening and is confirmed on Day -1, as determined by the investigator by MDRD formula. If the renal function classification for the participant changed from screening to Day -1, eGFR should be repeated once within 24 to 48 hours. If eGFR variability across these scheduled and repeat time points indicates the participant does not consistently meet the criteria for one renal category group, participant enrollment into a renal category group will be at the discretion of the medical monitor and investigator, in consultation with the Sponsor.

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.
• Intake of food supplements (including herbal preparations), foods or beverages that may affect cytochrome P450 (CYP) 3A4 (CYP3A4) 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 2 weeks before dosing until study discharge.
• Use of an herbal preparation containing Saint John's Wort within 4 weeks before dosing until study discharge.
• Known to be positive for human immunodeficiency virus.
• Presence of acute and active liver disease, or acute liver injury, as indicated by (1) an abnormal liver function test, or (2) clinical or laboratory signs of acute, active viral hepatitis (including B and C as demonstrated by positive serology at Screening). Participants with stable, chronic, inactive viral hepatitis B or C may be enrolled based on investigator's opinion.
• Corrected QT interval for heart rate on electrocardiograms (ECGs) by Fridericia's formula (QTcF) \>480 milliseconds (msec) at Screening or Day -1. Before excluding a participant with QTcF \>480 msec at Screening, ECG should be repeated once to confirm.
• A known or suspected history of drug or alcohol abuse disorder within 6 months prior to Screening.
• A positive urine drug test or a positive breathalyzer alcohol test at Screening or Day -1.
• Participation in another interventional clinical trial within 4 weeks, or 5 times the half-life of the investigational drug (whichever is longer), of lemborexant administration.
• Engaged in heavy/strenuous physical exercise within 2 weeks prior to check-in on Day -1 (e.g., marathon runners, weight lifters).
• Unwilling to abide by the study requirements, or in the opinion of the investigator, is not likely to complete the study.
• History of clinically significant drug or food allergies, or is presently experiencing significant seasonal allergies.
• Recent weight change that is considered clinically significant by the Investigator.
• Clinically significant findings revealed by physical examination, assessment of vital signs, ECG, or clinical laboratory testing.

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

Conditions

Renal Insufficiency

Interventions

lemborexant

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

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: No

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 16, 2018
• First Posted: February 22, 2018
• Study Start: February 7, 2018
• Primary Completion: August 24, 2018
• Study Completion: August 24, 2018
• Last Updated: March 12, 2020
• Results First Posted: January 18, 2020

Record last verified: 2018-07

Locations

US (2)