Study to Evaluate the Pharmacokinetics of Lemborexant (E2... | NCT03443063

Name	Class
Purdue Pharma LP	INDUSTRY

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Lemborexant	Drug	oral tablet	Group 1: Severe Renal Impairment Group 2: Normal Renal Function

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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

Eligibility Module

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.

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Pharmacology of Miami, LLC		Miami	Florida	33014	United States
Orlando Clinical Research Center

ID	Title	Description
FG000	Lemborexant: 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) received a single dose of 10 milligrams (mg) lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 2, 2018	Feb 3, 2020

ID	Title	Description
BG000	Lemborexant: Severe Renal Impairment	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.
BG001	Lemborexant: Normal Renal Function	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0008 BG0018 BG00216

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Observed Plasma Concentration (Cmax) of Lemborexant

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter (ng/mL)

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants	OG0008 OG0018

Title

Denominators

Categories

Title	Measurements
	OG00048.9± 41.0 OG00146.6± 29.2

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Percent (%) ratio of geometric means	104.83			2-Sided	90	77.41	141.97			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.		Other

Primary

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

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour*nanogram per milliliter (h*ng/mL)

Day 1: predose, 0.5 up to 72 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants

Primary

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

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants

Primary

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

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants

Secondary

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

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants

Secondary

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

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.

Posted

Median

Full Range

hour (h)

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants	OG000

Secondary

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)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1: predose, 0.5 up to 8 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants

Secondary

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)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1: predose, 0.5 up to 72 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants

Secondary

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)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants

Secondary

Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants

Secondary

Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10)

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).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Secondary

Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10)

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

percentage of AUCex

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Secondary

Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10)

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.

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.

Posted

Median

Full Range

hour (h)

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Secondary

Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10)

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

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

per hour (1/h)

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Secondary

Apparent Body Clearance (CL/F) of Lemborexant

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

liter per hour (L/h)

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Secondary

Apparent Volume of Distribution (Vz/F) Based on the Terminal Phase of Lemborexant

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]).

Posted

Geometric Mean

Geometric Coefficient of Variation

liter (L)

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Secondary

Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Secondary

Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10)

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

% unbound

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Secondary

Apparent Clearance Relative to the Unbound Plasma Concentration (CLu/F) Based on AUCu of Lemborexant

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

Posted

Geometric Mean

Geometric Coefficient of Variation

liter per hour (L/h)

Day 1: predose, 0.5 up to 240 hours postdose

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.

Posted

Count of Participants

Participants

Up to Day 11

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Clinically Significant Laboratory Abnormalities

The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.

Posted

Count of Participants

Participants

Up to Day 11

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Clinically Significant Abnormal Vital Sign Values

The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.

Posted

Count of Participants

Participants

Up to Day 11

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Parameter Values

The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.

Posted

Count of Participants

Participants

Up to Day 11

ID	Title	Description
OG000	Lemborexant: Severe Renal Impairment	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.
OG001	Lemborexant: Normal Renal Function	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.

Units	Counts
Participants	OG000

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lemborexant: Severe Renal Impairment	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.	0	8	0	8	5	8
EG001	Lemborexant: Normal Renal Function	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.	0	8	0	8	7	8

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Chills	General disorders	MedDRA (20.1)	Systematic Assessment		EG0001 affected8 at risk EG0010 affected8 at risk
Somnolence	Nervous system disorders	MedDRA (20.1)	Systematic Assessment		EG0005 affected8 at risk EG0017 affected8 at risk

ID	Term
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases