Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Normal Renal Function or With Severe Renal Impairment
Condition: Renal Impairment
MeSH terms: Renal Insufficiency
Intervention: Lemborexant
Intervention description: oral tablet
Intervention MeSH terms: Lemborexant
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: severe renal impairment; lemborexant; normal renal function; healthy participants; metabolites; E2006; pharmacokinetics

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

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 -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.