Renal Impairment
Conditions
Keywords
severe renal impairment, lemborexant, normal renal function, healthy participants, metabolites, E2006, pharmacokinetics
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.
Interventions
DRUGLemborexant
oral tablet
Sponsors
Purdue Pharma LP
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
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.
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10) | Day 1: predose, 0.5 up to 240 hours postdose | — |
| Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Day 1: predose, 0.5 up to 240 hours postdose | 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. |
| 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. |
| 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to Day 11 | — |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Up to Day 11 | — |
| Number of Participants With Clinically Significant Abnormal Vital Sign Values | Up to Day 11 | — |
| Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Parameter Values | Up to Day 11 | — |
| 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 /(\[ λz\]\*\[AUC0-inf\]). |
| Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10) | Day 1: predose, 0.5 up to 240 hours postdose | — |
| Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose (AUC[0-8h]) of Lemborexant and Its Metabolites (M4, M9, and M10) | Day 1: predose, 0.5 up to 8 hours postdose | — |
| Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Post Dose (AUC[0-72h]) of Metabolites of Lemborexant (M4, M9, and M10) | Day 1: predose, 0.5 up to 72 hours postdose | — |
Countries
United States
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 details
A total of 48 participants were screened, of which 32 were screen failures and 16 were enrolled and received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 8 |
| 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. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Lemborexant: Normal Renal Function | Total | Lemborexant: Severe Renal Impairment |
|---|---|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 7.91 | 66.9 years STANDARD_DEVIATION 6.56 | 67.4 years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 16 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 5 / 8 | 7 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Lemborexant
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Lemborexant | 672 h*ng/mL | Geometric Coefficient of Variation 19.6 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Lemborexant | 449 h*ng/mL | Geometric Coefficient of Variation 38.3 |
90% CI: [113.06, 198.58]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Post Dose (AUC[0-72h]) of Lemborexant
Time frame: Day 1: predose, 0.5 up to 72 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Post Dose (AUC[0-72h]) of Lemborexant | 419 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 21.9 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Post Dose (AUC[0-72h]) of Lemborexant | 315 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27.4 |
90% CI: [107.3, 164.93]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of Lemborexant
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of Lemborexant | 660 h*ng/mL | Geometric Coefficient of Variation 29.3 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of Lemborexant | 439 h*ng/mL | Geometric Coefficient of Variation 36.9 |
90% CI: [113.16, 200.26]
Primary
Maximum Observed Plasma Concentration (Cmax) of Lemborexant
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Lemborexant | 48.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| Lemborexant: Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Lemborexant | 46.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 29.2 |
90% CI: [77.41, 141.97]
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.
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Apparent Body Clearance (CL/F) of Lemborexant | 14.9 liter per hour (L/h) | Geometric Coefficient of Variation 19.6 |
| Lemborexant: Normal Renal Function | Apparent Body Clearance (CL/F) of Lemborexant | 22.3 liter per hour (L/h) | Geometric Coefficient of Variation 38.3 |
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.
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Apparent Clearance Relative to the Unbound Plasma Concentration (CLu/F) Based on AUCu of Lemborexant | 219 liter per hour (L/h) | Geometric Coefficient of Variation 16.9 |
| Lemborexant: Normal Renal Function | Apparent Clearance Relative to the Unbound Plasma Concentration (CLu/F) Based on AUCu of Lemborexant | 309 liter per hour (L/h) | Geometric Coefficient of Variation 44.3 |
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 /(\[ λz\]\*\[AUC0-inf\]).
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Apparent Volume of Distribution (Vz/F) Based on the Terminal Phase of Lemborexant | 1570 liter (L) | Geometric Coefficient of Variation 32.8 |
| Lemborexant: Normal Renal Function | Apparent Volume of Distribution (Vz/F) Based on the Terminal Phase of Lemborexant | 2180 liter (L) | Geometric Coefficient of Variation 46.3 |
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).
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 45.7 h*ng/mL | Geometric Coefficient of Variation 16.9 |
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 57.8 h*ng/mL | Geometric Coefficient of Variation 12.6 |
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 16.6 h*ng/mL | Geometric Coefficient of Variation 13.3 |
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 32.1 h*ng/mL | Geometric Coefficient of Variation 28.2 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 22.9 h*ng/mL | Geometric Coefficient of Variation 36.5 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 32.4 h*ng/mL | Geometric Coefficient of Variation 44.3 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 11.6 h*ng/mL | Geometric Coefficient of Variation 38 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve Adjusted by Unbound Fraction of Plasma (AUCu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 46.4 h*ng/mL | Geometric Coefficient of Variation 27 |
Comparison: Lemborexant90% CI: [103.79, 191.73]
Comparison: Metabolite M490% CI: [100.58, 154.06]
Comparison: Metabolite M990% CI: [107.72, 190.65]
Comparison: Metabolite M1090% CI: [98.11, 200.35]
Secondary
Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10)
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M4 | 248 h*ng/mL | Geometric Coefficient of Variation 20.4 |
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M9 | 108 h*ng/mL | Geometric Coefficient of Variation 24.1 |
| Lemborexant: Severe Renal Impairment | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M10 | 357 h*ng/mL | Geometric Coefficient of Variation 20.1 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M4 | 179 h*ng/mL | Geometric Coefficient of Variation 29.9 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M9 | 73.5 h*ng/mL | Geometric Coefficient of Variation 38.8 |
| Lemborexant: Normal Renal Function | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M10 | 262 h*ng/mL | Geometric Coefficient of Variation 36.7 |
Comparison: Metabolite M490% CI: [109.1, 176.14]
Comparison: Metabolite M990% CI: [109.06, 198.22]
Comparison: Metabolite M1090% CI: [98.19, 189.54]
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)
Time frame: Day 1: predose, 0.5 up to 72 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | 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) | Metabolite M4 | 164 h*ng/mL | Geometric Coefficient of Variation 19 |
| Lemborexant: Severe Renal Impairment | 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) | Metabolite M9 | 67.2 h*ng/mL | Geometric Coefficient of Variation 16.8 |
| Lemborexant: Severe Renal Impairment | 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) | Metabolite M10 | 149 h*ng/mL | Geometric Coefficient of Variation 40.2 |
| Lemborexant: Normal Renal Function | 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) | Metabolite M4 | 143 h*ng/mL | Geometric Coefficient of Variation 25.3 |
| Lemborexant: Normal Renal Function | 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) | Metabolite M9 | 53.8 h*ng/mL | Geometric Coefficient of Variation 31.9 |
| Lemborexant: Normal Renal Function | 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) | Metabolite M10 | 162 h*ng/mL | Geometric Coefficient of Variation 34.7 |
Comparison: Metabolite M490% CI: [94.45, 139.28]
Comparison: Metabolite M990% CI: [100.27, 155.67]
Comparison: Metabolite M1090% CI: [66.87, 126.71]
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)
Time frame: Day 1: predose, 0.5 up to 8 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | 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) | Lemborexant | 159 h*ng/mL | Geometric Coefficient of Variation 23.2 |
| Lemborexant: Severe Renal Impairment | 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) | Metabolite M4 | 36.9 h*ng/mL | Geometric Coefficient of Variation 46.2 |
| Lemborexant: Severe Renal Impairment | 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) | Metabolite M9 | 16.7 h*ng/mL | Geometric Coefficient of Variation 31.8 |
| Lemborexant: Severe Renal Impairment | 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) | Metabolite M10 | 15.9 h*ng/mL | Geometric Coefficient of Variation 63.8 |
| Lemborexant: Normal Renal Function | 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) | Metabolite M10 | 24.4 h*ng/mL | Geometric Coefficient of Variation 49.1 |
| Lemborexant: Normal Renal Function | 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) | Lemborexant | 143 h*ng/mL | Geometric Coefficient of Variation 21.2 |
| Lemborexant: Normal Renal Function | 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) | Metabolite M9 | 19.2 h*ng/mL | Geometric Coefficient of Variation 35.7 |
| Lemborexant: Normal Renal Function | 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) | Metabolite M4 | 45.9 h*ng/mL | Geometric Coefficient of Variation 34.9 |
Comparison: Lemborexant90% CI: [91.69, 134.99]
Comparison: Metabolite M490% CI: [56.81, 113.46]
Comparison: Metabolite M990% CI: [64.92, 115.81]
Comparison: Metabolite M1090% CI: [41.08, 104.04]
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)
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | 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) | Metabolite M4 | 247 h*ng/mL | Geometric Coefficient of Variation 25.9 |
| Lemborexant: Severe Renal Impairment | 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) | Metabolite M9 | 106 h*ng/mL | Geometric Coefficient of Variation 27 |
| Lemborexant: Severe Renal Impairment | 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) | Metabolite M10 | 322 h*ng/mL | Geometric Coefficient of Variation 28.3 |
| Lemborexant: Normal Renal Function | 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) | Metabolite M4 | 181 h*ng/mL | Geometric Coefficient of Variation 32.9 |
| Lemborexant: Normal Renal Function | 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) | Metabolite M9 | 68.7 h*ng/mL | Geometric Coefficient of Variation 35.8 |
| Lemborexant: Normal Renal Function | 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) | Metabolite M10 | 272 h*ng/mL | Geometric Coefficient of Variation 40.9 |
Comparison: Metabolite M490% CI: [105.62, 175.85]
Comparison: Metabolite M990% CI: [117.53, 202.57]
Comparison: Metabolite M1090% CI: [87.84, 159.97]
Secondary
Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10)
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M4 | 6.37 ng/mL | Geometric Coefficient of Variation 44.8 |
| Lemborexant: Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M9 | 3.77 ng/mL | Geometric Coefficient of Variation 44.1 |
| Lemborexant: Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M10 | 2.78 ng/mL | Geometric Coefficient of Variation 50.5 |
| Lemborexant: Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M4 | 7.96 ng/mL | Geometric Coefficient of Variation 39.5 |
| Lemborexant: Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M9 | 4.74 ng/mL | Geometric Coefficient of Variation 45.9 |
| Lemborexant: Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M10 | 3.83 ng/mL | Geometric Coefficient of Variation 48 |
Comparison: Metabolite M490% CI: [56.07, 114.4]
Comparison: Metabolite M990% CI: [54.48, 116.03]
Comparison: Metabolite M1090% CI: [48.08, 109.29]
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.
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M4 | 0.355 ratio | Geometric Coefficient of Variation 7.49 |
| Lemborexant: Severe Renal Impairment | Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M9 | 0.155 ratio | Geometric Coefficient of Variation 18.5 |
| Lemborexant: Severe Renal Impairment | Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M10 | 0.549 ratio | Geometric Coefficient of Variation 13.4 |
| Lemborexant: Normal Renal Function | Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M4 | 0.384 ratio | Geometric Coefficient of Variation 13.6 |
| Lemborexant: Normal Renal Function | Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M9 | 0.150 ratio | Geometric Coefficient of Variation 31.7 |
| Lemborexant: Normal Renal Function | Metabolite-to-Parent Ratio of AUC(0-inf), Corrected for Molecular Weights (MPR AUC[0-inf]) of Metabolites of Lemborexant (M4, M9, and M10) | Metabolite M10 | 0.612 ratio | Geometric Coefficient of Variation 10.3 |
Secondary
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Parameter Values
Time frame: Up to Day 11
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lemborexant: Severe Renal Impairment | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Parameter Values | 0 Participants |
| Lemborexant: Normal Renal Function | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Parameter Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormal Vital Sign Values
Time frame: Up to Day 11
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lemborexant: Severe Renal Impairment | Number of Participants With Clinically Significant Abnormal Vital Sign Values | 0 Participants |
| Lemborexant: Normal Renal Function | Number of Participants With Clinically Significant Abnormal Vital Sign Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities
Time frame: Up to Day 11
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lemborexant: Severe Renal Impairment | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Lemborexant: Normal Renal Function | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to Day 11
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 5 Participants |
| Lemborexant: Severe Renal Impairment | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Lemborexant: Normal Renal Function | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| Lemborexant: Normal Renal Function | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
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.
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 0.00950 per hour (1/h) | Geometric Coefficient of Variation 25.4 |
| Lemborexant: Severe Renal Impairment | Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 0.0108 per hour (1/h) | Geometric Coefficient of Variation 21.5 |
| Lemborexant: Severe Renal Impairment | Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 0.0113 per hour (1/h) | Geometric Coefficient of Variation 29.7 |
| Lemborexant: Severe Renal Impairment | Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 0.0111 per hour (1/h) | Geometric Coefficient of Variation 30.5 |
| Lemborexant: Normal Renal Function | Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 0.0114 per hour (1/h) | Geometric Coefficient of Variation 39.2 |
| Lemborexant: Normal Renal Function | Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 0.0102 per hour (1/h) | Geometric Coefficient of Variation 28.7 |
| Lemborexant: Normal Renal Function | Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 0.0142 per hour (1/h) | Geometric Coefficient of Variation 47.8 |
| Lemborexant: Normal Renal Function | Observed Elimination Rate Constant (LambdaZ) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 0.0114 per hour (1/h) | Geometric Coefficient of Variation 30.2 |
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.
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 79.5 hour (h) |
| Lemborexant: Severe Renal Impairment | Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 68.1 hour (h) |
| Lemborexant: Severe Renal Impairment | Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 64.1 hour (h) |
| Lemborexant: Severe Renal Impairment | Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 63.4 hour (h) |
| Lemborexant: Normal Renal Function | Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 70.5 hour (h) |
| Lemborexant: Normal Renal Function | Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 79.7 hour (h) |
| Lemborexant: Normal Renal Function | Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 53.5 hour (h) |
| Lemborexant: Normal Renal Function | Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 67.0 hour (h) |
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.
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 7.65 percentage of AUCex | Geometric Coefficient of Variation 73.1 |
| Lemborexant: Severe Renal Impairment | Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 5.35 percentage of AUCex | Geometric Coefficient of Variation 75.2 |
| Lemborexant: Severe Renal Impairment | Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 6.72 percentage of AUCex | Geometric Coefficient of Variation 69 |
| Lemborexant: Severe Renal Impairment | Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 7.46 percentage of AUCex | Geometric Coefficient of Variation 79.5 |
| Lemborexant: Normal Renal Function | Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 7.16 percentage of AUCex | Geometric Coefficient of Variation 74.1 |
| Lemborexant: Normal Renal Function | Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 5.74 percentage of AUCex | Geometric Coefficient of Variation 85.7 |
| Lemborexant: Normal Renal Function | Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 6.15 percentage of AUCex | Geometric Coefficient of Variation 30.3 |
| Lemborexant: Normal Renal Function | Percentage of AUC(0-inf) Based on Extrapolation (AUCex) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 4.88 percentage of AUCex | Geometric Coefficient of Variation 24.6 |
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.
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 6.68 % unbound | Geometric Coefficient of Variation 10.4 |
| Lemborexant: Severe Renal Impairment | Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 24.1 % unbound | Geometric Coefficient of Variation 11.4 |
| Lemborexant: Severe Renal Impairment | Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 15.7 % unbound | Geometric Coefficient of Variation 12.5 |
| Lemborexant: Severe Renal Impairment | Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 8.18 % unbound | Geometric Coefficient of Variation 27.5 |
| Lemborexant: Normal Renal Function | Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 8.63 % unbound | Geometric Coefficient of Variation 11.9 |
| Lemborexant: Normal Renal Function | Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 7.11 % unbound | Geometric Coefficient of Variation 10.7 |
| Lemborexant: Normal Renal Function | Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 16.1 % unbound | Geometric Coefficient of Variation 8.79 |
| Lemborexant: Normal Renal Function | Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 25.5 % unbound | Geometric Coefficient of Variation 6.9 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10)
Time frame: Day 1: predose, 0.5 up to 240 hours postdose
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lemborexant: Severe Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 1.00 hour (h) |
| Lemborexant: Severe Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 1.00 hour (h) |
| Lemborexant: Severe Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 5.00 hour (h) |
| Lemborexant: Severe Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 3.50 hour (h) |
| Lemborexant: Normal Renal Function | Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M9 | 1.25 hour (h) |
| Lemborexant: Normal Renal Function | Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10) | Lemborexant | 1.00 hour (h) |
| Lemborexant: Normal Renal Function | Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M4 | 2.00 hour (h) |
| Lemborexant: Normal Renal Function | Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10) | Metabolite M10 | 3.00 hour (h) |