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

Sponsor
Eisai Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03443063
Collaborator
Purdue Pharma LP (Industry)
16
2
2
6.5
8
1.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Feb 7, 2018
Actual Primary Completion Date :
Aug 24, 2018
Actual Study Completion Date :
Aug 24, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Lemborexant
oral tablet
Other Names:
  • E2006
  • Experimental: 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.

    Drug: Lemborexant
    oral tablet
    Other Names:
  • E2006
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Observed Plasma Concentration (Cmax) of Lemborexant [Day 1: predose, 0.5 up to 240 hours postdose]

    2. 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]

    3. 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]

    4. 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 Outcome Measures

    1. Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10) [Day 1: predose, 0.5 up to 240 hours postdose]

    2. 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]

    3. 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]

    4. 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]

    5. 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]

    6. 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]

    7. 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]

      AUCu was defined as the AUC(0-inf) adjusted by unbound fraction in plasma, and calculated by multiplying the value of AUC(0-inf) with Plasma protein unbound fraction (fu).

    8. 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]

      AUCex was calculated by dividing the difference of (AUC(0-inf) and AUC(0-t)) by value of AUC(0-inf) and then multiplying the value by 100.

    9. 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]

      Terminal plasma half-life is the time required for plasma/blood concentration to decrease by 50%. This is not the time required to eliminate half the administered dose.

    10. Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10) [Day 1: predose, 0.5 up to 240 hours postdose]

      Estimated by linear regression through at least three data points (not including tmax) in the terminal phase of the log concentration-time profile.

    11. Apparent Body Clearance (CL/F) of Lemborexant [Day 1: predose, 0.5 up to 240 hours postdose]

      CL/F is the clearance for parent Lemborexant only and was calculated as Dose/[AUC0-inf]. Blood samples were analyzed for the amount of Lemborexant in the plasma.

    12. Apparent Volume of Distribution (Vz/F) Based on the Terminal Phase of Lemborexant [Day 1: predose, 0.5 up to 240 hours postdose]

      The apparent volume of distribution gives information about the amount of Lemborexant distributed in body tissue rather than the blood/plasma. Vz/F for parent Lemborexant only was calculated as Dose /([ λz]*[AUC0-inf]).

    13. 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]

      The AUC metabolite to parent ratio (MPR) is the ratio of AUC(0-inf) of the individual metabolite to AUC(0-inf) of lemborexant, corrected for molecular weights.

    14. Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10) [Day 1: predose, 0.5 up to 240 hours postdose]

      Unbound fraction of drug in plasma was calculated as 100% minus (-) mean percent of Lemborexant and Its Metabolites M4. M9. M10 bound to plasma protein for each participant.

    15. 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]

      Unbound fraction of drug in plasma was calculated as 100% - mean percent of Lemborexant bound to plasma protein for each participant.

    16. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Up to Day 11]

    17. Number of Participants With Clinically Significant Laboratory Abnormalities [Up to Day 11]

    18. Number of Participants With Clinically Significant Abnormal Vital Sign Values [Up to Day 11]

    19. Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Parameter Values [Up to Day 11]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 79 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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 -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.

    • Use of any prohibited prescription or over-the-counter medication within 2 weeks or 5 half-lives (whichever is longer) before Screening, or plans to use any such treatment during the study. For participants with renal impairment, chronic stable administration of medications necessary for maintaining the clinical status of the participant may be permitted after consultation with the Medical Monitor.

    Additional Exclusion Criteria for Healthy Participants:
    • Presence of clinically significant illness requiring treatment or that may influence the outcome of the study (e.g., psychiatric disorders, disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system), a history of myocardial infraction, or a congenital abnormality.

    • Receipt or donation of blood or blood products within 4 to 8 weeks prior to study drug administration.

    Additional Exclusion Criteria for Participants With Renal Impairment:
    • Any history of renal transplant.

    • Any known significant bleeding diathesis (e.g., history of recent bleeding from esophageal varices), which could preclude multiple venipuncture or deep intramuscular injections.

    • New significant illness that onset within 2 weeks prior to study drug administration.

    • Current clinically relevant disease other than the renal impairment (e.g., cardiac, hepatic, gastrointestinal disorder, or a condition which may impact drug absorption), as determined by the investigator. Participants with a history of Type I or Type II diabetes may be eligible, providing that, in the investigator's opinion, the disease has been stable. Participants receiving insulin therapy may be eligible provided they have been on a stable (i.e., dose has not changed) treatment for at least 2 weeks prior to study enrollment and will continue the treatment throughout the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Pharmacology of Miami, LLC Miami Florida United States 33014
    2 Orlando Clinical Research Center Orlando Florida United States 32809

    Sponsors and Collaborators

    • Eisai Inc.
    • Purdue Pharma LP

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Eisai Inc.
    ClinicalTrials.gov Identifier:
    NCT03443063
    Other Study ID Numbers:
    • E2006-A001-105
    First Posted:
    Feb 22, 2018
    Last Update Posted:
    Mar 12, 2020
    Last Verified:
    Jul 1, 2018
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Eisai Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants took part in the study at 2 investigative sites in the United states from 07 February 2018 to 24 August 2018.
    Pre-assignment Detail A total of 48 participants were screened, of which 32 were screen failures and 16 were enrolled and received study treatment.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description 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) received a single dose of 10 milligrams (mg) lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR greater than or equal to (>=) 90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and body mass index [BMI]) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Period Title: Overall Study
    STARTED 8 8
    COMPLETED 8 8
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function Total
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Total of all reporting groups
    Overall Participants 8 8 16
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    67.4
    (5.40)
    66.5
    (7.91)
    66.9
    (6.56)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    8
    100%
    8
    100%
    16
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    5
    62.5%
    5
    62.5%
    10
    62.5%
    Not Hispanic or Latino
    3
    37.5%
    3
    37.5%
    6
    37.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    8
    100%
    8
    100%
    16
    100%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Observed Plasma Concentration (Cmax) of Lemborexant
    Description
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]
    48.9
    (41.0)
    46.6
    (29.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 104.83
    Confidence Interval (2-Sided) 90%
    77.41 to 141.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    2. Primary Outcome
    Title Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Post Dose (AUC[0-72h]) of Lemborexant
    Description
    Time Frame Day 1: predose, 0.5 up to 72 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Geometric Mean (Geometric Coefficient of Variation) [hour*nanogram per milliliter (h*ng/mL)]
    419
    (21.9)
    315
    (27.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 133.03
    Confidence Interval (2-Sided) 90%
    107.30 to 164.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    3. Primary Outcome
    Title Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of Lemborexant
    Description
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
    660
    (29.3)
    439
    (36.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 150.53
    Confidence Interval (2-Sided) 90%
    113.16 to 200.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    4. Primary Outcome
    Title Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Lemborexant
    Description
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "overall number of participants analyzed" signifies the participants who were evaluable for analysis for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 7 7
    Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]
    672
    (19.6)
    449
    (38.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 149.84
    Confidence Interval (2-Sided) 90%
    113.06 to 198.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    5. Secondary Outcome
    Title Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10)
    Description
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Metabolite M4
    6.37
    (44.8)
    7.96
    (39.5)
    Metabolite M9
    3.77
    (44.1)
    4.74
    (45.9)
    Metabolite M10
    2.78
    (50.5)
    3.83
    (48.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 80.09
    Confidence Interval (2-Sided) 90%
    56.07 to 114.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M9
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 79.51
    Confidence Interval (2-Sided) 90%
    54.48 to 116.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M10
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 72.49
    Confidence Interval (2-Sided) 90%
    48.08 to 109.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    6. Secondary Outcome
    Title Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10)
    Description
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Lemborexant
    1.00
    1.00
    Metabolite M4
    3.50
    2.00
    Metabolite M9
    1.00
    1.25
    Metabolite M10
    5.00
    3.00
    7. Secondary Outcome
    Title 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)
    Description
    Time Frame Day 1: predose, 0.5 up to 8 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Lemborexant
    159
    (23.2)
    143
    (21.2)
    Metabolite M4
    36.9
    (46.2)
    45.9
    (34.9)
    Metabolite M9
    16.7
    (31.8)
    19.2
    (35.7)
    Metabolite M10
    15.9
    (63.8)
    24.4
    (49.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Lemborexant
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric mean
    Estimated Value 111.25
    Confidence Interval (2-Sided) 90%
    91.69 to 134.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 80.28
    Confidence Interval (2-Sided) 90%
    56.81 to 113.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M9
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 86.71
    Confidence Interval (2-Sided) 90%
    64.92 to 115.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M10
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 65.38
    Confidence Interval (2-Sided) 90%
    41.08 to 104.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    8. Secondary Outcome
    Title 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)
    Description
    Time Frame Day 1: predose, 0.5 up to 72 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Metabolite M4
    164
    (19.0)
    143
    (25.3)
    Metabolite M9
    67.2
    (16.8)
    53.8
    (31.9)
    Metabolite M10
    149
    (40.2)
    162
    (34.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 114.69
    Confidence Interval (2-Sided) 90%
    94.45 to 139.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M9
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 124.94
    Confidence Interval (2-Sided) 90%
    100.27 to 155.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M10
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 92.05
    Confidence Interval (2-Sided) 90%
    66.87 to 126.71
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    9. Secondary Outcome
    Title 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)
    Description
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Metabolite M4
    247
    (25.9)
    181
    (32.9)
    Metabolite M9
    106
    (27.0)
    68.7
    (35.8)
    Metabolite M10
    322
    (28.3)
    272
    (40.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 136.28
    Confidence Interval (2-Sided) 90%
    105.62 to 175.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M9
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 154.29
    Confidence Interval (2-Sided) 90%
    117.53 to 202.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M10
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 118.54
    Confidence Interval (2-Sided) 90%
    87.84 to 159.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    10. Secondary Outcome
    Title Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10)
    Description
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "number analyzed" signifies the participants who were evaluable for analysis for specific metabolite of lemborexant for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Metabolite M4
    248
    (20.4)
    179
    (29.9)
    Metabolite M9
    108
    (24.1)
    73.5
    (38.8)
    Metabolite M10
    357
    (20.1)
    262
    (36.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 138.62
    Confidence Interval (2-Sided) 90%
    109.10 to 176.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M9
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 147.03
    Confidence Interval (2-Sided) 90%
    109.06 to 198.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M10
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 136.42
    Confidence Interval (2-Sided) 90%
    98.19 to 189.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    11. Secondary Outcome
    Title Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10)
    Description AUCu was defined as the AUC(0-inf) adjusted by unbound fraction in plasma, and calculated by multiplying the value of AUC(0-inf) with Plasma protein unbound fraction (fu).
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "number analyzed" signifies the participants who were evaluable for analysis for lemborexant and for specific metabolite of lemborexant for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Lemborexant
    45.7
    (16.9)
    32.4
    (44.3)
    Metabolite M4
    57.8
    (12.6)
    46.4
    (27.0)
    Metabolite M9
    16.6
    (13.3)
    11.6
    (38.0)
    Metabolite M10
    32.1
    (28.2)
    22.9
    (36.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Lemborexant
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 141.07
    Confidence Interval (2-Sided) 90%
    103.79 to 191.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M4
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 124.48
    Confidence Interval (2-Sided) 90%
    100.58 to 154.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M9
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 143.31
    Confidence Interval (2-Sided) 90%
    107.72 to 190.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Lemborexant: Severe Renal Impairment, Lemborexant: Normal Renal Function
    Comments Metabolite M10
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent (%) ratio of geometric means
    Estimated Value 140.20
    Confidence Interval (2-Sided) 90%
    98.11 to 200.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent ratio was calculated by dividing the geometric mean of reporting arm "Lemborexant: Severe Renal Impairment" by geometric mean of reporting arm "Lemborexant: Normal Renal Function", then multiplying the value by 100.
    12. Secondary Outcome
    Title Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10)
    Description AUCex was calculated by dividing the difference of (AUC(0-inf) and AUC(0-t)) by value of AUC(0-inf) and then multiplying the value by 100.
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "number analyzed" signifies the participants who were evaluable for analysis for lemborexant and for specific metabolite of lemborexant for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Lemborexant
    7.65
    (73.1)
    5.74
    (85.7)
    Metabolite M4
    5.35
    (75.2)
    4.88
    (24.6)
    Metabolite M9
    6.72
    (69.0)
    6.15
    (30.3)
    Metabolite M10
    7.46
    (79.5)
    7.16
    (74.1)
    13. Secondary Outcome
    Title Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10)
    Description Terminal plasma half-life is the time required for plasma/blood concentration to decrease by 50%. This is not the time required to eliminate half the administered dose.
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "number analyzed" signifies the participants who were evaluable for analysis for lemborexant and for specific metabolite of lemborexant for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Lemborexant
    79.5
    79.7
    Metabolite M4
    68.1
    67.0
    Metabolite M9
    64.1
    53.5
    Metabolite M10
    63.4
    70.5
    14. Secondary Outcome
    Title Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10)
    Description Estimated by linear regression through at least three data points (not including tmax) in the terminal phase of the log concentration-time profile.
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "number analyzed" signifies the participants who were evaluable for analysis for lemborexant and for specific metabolite of lemborexant for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) in the morning on Day 1 after an overnight fast.
    Measure Participants 8 8
    Lemborexant
    0.00950
    (25.4)
    0.0102
    (28.7)
    Metabolite M4
    0.0108
    (21.5)
    0.0114
    (30.2)
    Metabolite M9
    0.0113
    (29.7)
    0.0142
    (47.8)
    Metabolite M10
    0.0111
    (30.5)
    0.0114
    (39.2)
    15. Secondary Outcome
    Title Apparent Body Clearance (CL/F) of Lemborexant
    Description CL/F is the clearance for parent Lemborexant only and was calculated as Dose/[AUC0-inf]. Blood samples were analyzed for the amount of Lemborexant in the plasma.
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "overall number of participants analyzed" signifies the participants who were evaluable for analysis for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 7 7
    Geometric Mean (Geometric Coefficient of Variation) [liter per hour (L/h)]
    14.9
    (19.6)
    22.3
    (38.3)
    16. Secondary Outcome
    Title Apparent Volume of Distribution (Vz/F) Based on the Terminal Phase of Lemborexant
    Description The apparent volume of distribution gives information about the amount of Lemborexant distributed in body tissue rather than the blood/plasma. Vz/F for parent Lemborexant only was calculated as Dose /([ λz]*[AUC0-inf]).
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "overall number of participants analyzed" signifies the participants who were evaluable for analysis for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 7 7
    Geometric Mean (Geometric Coefficient of Variation) [liter (L)]
    1570
    (32.8)
    2180
    (46.3)
    17. Secondary Outcome
    Title Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10)
    Description The AUC metabolite to parent ratio (MPR) is the ratio of AUC(0-inf) of the individual metabolite to AUC(0-inf) of lemborexant, corrected for molecular weights.
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "number analyzed" signifies the participants who were evaluable for analysis for specific metabolite of lemborexant for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Metabolite M4
    0.355
    (7.49)
    0.384
    (13.6)
    Metabolite M9
    0.155
    (18.5)
    0.150
    (31.7)
    Metabolite M10
    0.549
    (13.4)
    0.612
    (10.3)
    18. Secondary Outcome
    Title Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10)
    Description Unbound fraction of drug in plasma was calculated as 100% minus (-) mean percent of Lemborexant and Its Metabolites M4. M9. M10 bound to plasma protein for each participant.
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "number analyzed" signifies the participants who were evaluable for analysis for lemborexant and for specific metabolite of lemborexant for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Lemborexant
    6.68
    (10.4)
    7.11
    (10.7)
    Metabolite M4
    24.1
    (11.4)
    25.5
    (6.90)
    Metabolite M9
    15.7
    (12.5)
    16.1
    (8.79)
    Metabolite M10
    8.18
    (27.5)
    8.63
    (11.9)
    19. Secondary Outcome
    Title Apparent Clearance Relative to the Unbound Plasma Concentration (CLu/F) Based on AUCu of Lemborexant
    Description Unbound fraction of drug in plasma was calculated as 100% - mean percent of Lemborexant bound to plasma protein for each participant.
    Time Frame Day 1: predose, 0.5 up to 240 hours postdose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was the group of participants who were dosed with the test drug and had sufficient PK data to derive at least one PK parameter. Here "overall number of participants analyzed" signifies the participants who were evaluable for analysis for this outcome measure.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 7 7
    Geometric Mean (Geometric Coefficient of Variation) [liter per hour (L/h)]
    219
    (16.9)
    309
    (44.3)
    20. Secondary Outcome
    Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    Description
    Time Frame Up to Day 11

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    TEAEs
    5
    62.5%
    7
    87.5%
    SAEs
    0
    0%
    0
    0%
    21. Secondary Outcome
    Title Number of Participants With Clinically Significant Laboratory Abnormalities
    Description
    Time Frame Up to Day 11

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Count of Participants [Participants]
    0
    0%
    0
    0%
    22. Secondary Outcome
    Title Number of Participants With Clinically Significant Abnormal Vital Sign Values
    Description
    Time Frame Up to Day 11

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Count of Participants [Participants]
    0
    0%
    0
    0%
    23. Secondary Outcome
    Title Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Parameter Values
    Description
    Time Frame Up to Day 11

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    Measure Participants 8 8
    Count of Participants [Participants]
    0
    0%
    0
    0%

    Adverse Events

    Time Frame Up to Day 11
    Adverse Event Reporting Description AEs were collected for the participants who were in the safety analysis set (all participants who were dosed with the test drug and had at least one postdose safety assessment).
    Arm/Group Title Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Arm/Group Description Participants with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m^2 and not on dialysis) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast. Participants with normal renal function (eGFR >=90 mL/min/1.73 m^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
    All Cause Mortality
    Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/8 (0%)
    Serious Adverse Events
    Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/8 (0%)
    Other (Not Including Serious) Adverse Events
    Lemborexant: Severe Renal Impairment Lemborexant: Normal Renal Function
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/8 (62.5%) 7/8 (87.5%)
    General disorders
    Chills 1/8 (12.5%) 0/8 (0%)
    Nervous system disorders
    Somnolence 5/8 (62.5%) 7/8 (87.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Eisai Medical Information
    Organization Eisai, Inc.
    Phone +1-888-274-2378
    Email esi_medinfo@eisai.com
    Responsible Party:
    Eisai Inc.
    ClinicalTrials.gov Identifier:
    NCT03443063
    Other Study ID Numbers:
    • E2006-A001-105
    First Posted:
    Feb 22, 2018
    Last Update Posted:
    Mar 12, 2020
    Last Verified:
    Jul 1, 2018