An Open-label, Parallel-Group Study to Evaluate the Pharmacokinetics of Lemborexant and Its Metabolites in Subjects With Normal Renal Function or With Severe Renal Impairment

Eisai Inc.2 sites in 1 country16 target enrollmentFebruary 7, 2018

ConditionsRenal Impairment

InterventionsLemborexant

DrugsLemborexant

Overview

Phase: Phase 1
Intervention: Lemborexant
Conditions: Renal Impairment
Sponsor: Eisai Inc.
Enrollment: 16
Locations: 2
Primary Endpoint: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Lemborexant
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

February 7, 2018

End Date

August 24, 2018

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Eisai Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Inclusion Criteria for All Participants:
•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.
•Additional Inclusion Criteria for Healthy Participants:
•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.
•Additional Inclusion Criteria for Participants with Renal Impairment:
•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.

Exclusion Criteria

•Exclusion Criteria for All Participants:
•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 -
•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.

Arms & Interventions

Group 1: Severe Renal Impairment

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.

Intervention: Lemborexant

Group 2: Normal Renal Function

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.

Intervention: Lemborexant

Outcomes

Primary Outcomes

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

Time Frame: 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

Time Frame: Day 1: predose, 0.5 up to 72 hours postdose

Maximum Observed Plasma Concentration (Cmax) of Lemborexant

Time Frame: Day 1: predose, 0.5 up to 240 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

Time Frame: Day 1: predose, 0.5 up to 240 hours postdose

Secondary Outcomes

Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (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 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)
Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) 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)
Number of Participants With Clinically Significant Laboratory Abnormalities(Up to Day 11)
Number of Participants With Clinically Significant Abnormal Vital Sign Values(Up to Day 11)
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 Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10)(Day 1: predose, 0.5 up to 240 hours postdose)
Apparent Volume of Distribution (Vz/F) Based on the Terminal Phase of Lemborexant(Day 1: predose, 0.5 up to 240 hours postdose)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to Day 11)
Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10)(Day 1: predose, 0.5 up to 240 hours postdose)
Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10)(Day 1: predose, 0.5 up to 240 hours postdose)
Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10)(Day 1: predose, 0.5 up to 240 hours postdose)
Apparent Body Clearance (CL/F) of Lemborexant(Day 1: predose, 0.5 up to 240 hours postdose)
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Parameter Values(Up to Day 11)
Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10)(Day 1: predose, 0.5 up to 240 hours postdose)
Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10)(Day 1: predose, 0.5 up to 240 hours postdose)
Apparent Clearance Relative to the Unbound Plasma Concentration (CLu/F) Based on AUCu of Lemborexant(Day 1: predose, 0.5 up to 240 hours postdose)