Trial Outcomes & Findings for Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Normal Renal Function or With Severe Renal Impairment (NCT NCT03443063)
NCT ID: NCT03443063
Last Updated: 2020-03-12
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Day 1: predose, 0.5 up to 240 hours postdose
Results posted on
2020-03-12
Participant Flow
Participants took part in the study at 2 investigative sites in the United states from 07 February 2018 to 24 August 2018.
A total of 48 participants were screened, of which 32 were screen failures and 16 were enrolled and received study treatment.
Participant milestones
| Measure |
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.
|
Lemborexant: Normal Renal Function
Participants with normal renal function (eGFR greater than or equal to (\>=) 90 mL/min/1.73 m\^2) demographically matched to participants with severe renal impairment (matched according to age, race, sex, and body mass index \[BMI\]) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Normal Renal Function or With Severe Renal Impairment
Baseline characteristics by cohort
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
Participants with normal renal function (eGFR \>=90 mL/min/1.73 m\^2) matched to participants with severe renal impairment (matched according to age, race, sex, and BMI) received a single dose of 10 mg lemborexant (oral tablet) on Day 1 in the morning after an overnight fast.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67.4 years
STANDARD_DEVIATION 5.40 • n=5 Participants
|
66.5 years
STANDARD_DEVIATION 7.91 • n=7 Participants
|
66.9 years
STANDARD_DEVIATION 6.56 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Lemborexant
|
48.9 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 41.0
|
46.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 29.2
|
PRIMARY outcome
Timeframe: Day 1: predose, 0.5 up to 72 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
315 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 27.4
|
PRIMARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
439 h*ng/mL
Geometric Coefficient of Variation 36.9
|
PRIMARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=7 Participants
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.
|
Lemborexant: Normal Renal Function
n=7 Participants
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.
|
|---|---|---|
|
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
|
449 h*ng/mL
Geometric Coefficient of Variation 38.3
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
7.96 ng/mL
Geometric Coefficient of Variation 39.5
|
|
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
|
4.74 ng/mL
Geometric Coefficient of Variation 45.9
|
|
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
|
3.83 ng/mL
Geometric Coefficient of Variation 48.0
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10)
Lemborexant
|
1.00 hour (h)
Interval 0.5 to 3.0
|
1.00 hour (h)
Interval 1.0 to 1.5
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10)
Metabolite M4
|
3.50 hour (h)
Interval 1.0 to 4.0
|
2.00 hour (h)
Interval 1.0 to 4.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10)
Metabolite M9
|
1.00 hour (h)
Interval 1.0 to 4.0
|
1.25 hour (h)
Interval 1.0 to 2.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Lemborexant and Its Metabolites (M4, M9, and M10)
Metabolite M10
|
5.00 hour (h)
Interval 3.0 to 72.17
|
3.00 hour (h)
Interval 2.0 to 4.0
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 8 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
143 h*ng/mL
Geometric Coefficient of Variation 21.2
|
|
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
|
45.9 h*ng/mL
Geometric Coefficient of Variation 34.9
|
|
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
|
19.2 h*ng/mL
Geometric Coefficient of Variation 35.7
|
|
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
|
24.4 h*ng/mL
Geometric Coefficient of Variation 49.1
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 72 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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 19.0
|
143 h*ng/mL
Geometric Coefficient of Variation 25.3
|
|
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
|
53.8 h*ng/mL
Geometric Coefficient of Variation 31.9
|
|
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
|
162 h*ng/mL
Geometric Coefficient of Variation 34.7
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
181 h*ng/mL
Geometric Coefficient of Variation 32.9
|
|
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 27.0
|
68.7 h*ng/mL
Geometric Coefficient of Variation 35.8
|
|
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
|
272 h*ng/mL
Geometric Coefficient of Variation 40.9
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
179 h*ng/mL
Geometric Coefficient of Variation 29.9
|
|
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
|
73.5 h*ng/mL
Geometric Coefficient of Variation 38.8
|
|
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
|
262 h*ng/mL
Geometric Coefficient of Variation 36.7
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
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).
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
32.4 h*ng/mL
Geometric Coefficient of Variation 44.3
|
|
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
|
46.4 h*ng/mL
Geometric Coefficient of Variation 27.0
|
|
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
|
11.6 h*ng/mL
Geometric Coefficient of Variation 38.0
|
|
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
|
22.9 h*ng/mL
Geometric Coefficient of Variation 36.5
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
5.74 percentage of AUCex
Geometric Coefficient of Variation 85.7
|
|
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
|
4.88 percentage of AUCex
Geometric Coefficient of Variation 24.6
|
|
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 69.0
|
6.15 percentage of AUCex
Geometric Coefficient of Variation 30.3
|
|
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
|
7.16 percentage of AUCex
Geometric Coefficient of Variation 74.1
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10)
Lemborexant
|
79.5 hour (h)
Interval 52.3 to 93.4
|
79.7 hour (h)
Interval 44.8 to 86.5
|
|
Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10)
Metabolite M4
|
68.1 hour (h)
Interval 47.5 to 83.1
|
67.0 hour (h)
Interval 38.1 to 82.8
|
|
Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10)
Metabolite M9
|
64.1 hour (h)
Interval 43.0 to 96.9
|
53.5 hour (h)
Interval 27.6 to 81.0
|
|
Observed Terminal Elimination Half-life (t1/2) of Lemborexant and Its Metabolites (M4, M9, and M10)
Metabolite M10
|
63.4 hour (h)
Interval 43.1 to 93.5
|
70.5 hour (h)
Interval 29.4 to 84.2
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
Estimated by linear regression through at least three data points (not including tmax) in the terminal phase of the log concentration-time profile.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
0.0102 per hour (1/h)
Geometric Coefficient of Variation 28.7
|
|
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
|
0.0114 per hour (1/h)
Geometric Coefficient of Variation 30.2
|
|
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
|
0.0142 per hour (1/h)
Geometric Coefficient of Variation 47.8
|
|
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
|
0.0114 per hour (1/h)
Geometric Coefficient of Variation 39.2
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=7 Participants
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.
|
Lemborexant: Normal Renal Function
n=7 Participants
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.
|
|---|---|---|
|
Apparent Body Clearance (CL/F) of Lemborexant
|
14.9 liter per hour (L/h)
Geometric Coefficient of Variation 19.6
|
22.3 liter per hour (L/h)
Geometric Coefficient of Variation 38.3
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
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 /(\[ λz\]\*\[AUC0-inf\]).
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=7 Participants
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.
|
Lemborexant: Normal Renal Function
n=7 Participants
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.
|
|---|---|---|
|
Apparent Volume of Distribution (Vz/F) Based on the Terminal Phase of Lemborexant
|
1570 liter (L)
Geometric Coefficient of Variation 32.8
|
2180 liter (L)
Geometric Coefficient of Variation 46.3
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
0.384 ratio
Geometric Coefficient of Variation 13.6
|
|
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
|
0.150 ratio
Geometric Coefficient of Variation 31.7
|
|
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
|
0.612 ratio
Geometric Coefficient of Variation 10.3
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
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.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
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
|
16.1 % unbound
Geometric Coefficient of Variation 8.79
|
|
Plasma Protein Unbound Fraction (Fu) of Lemborexant and Its Metabolites (M4, M9, and M10)
Lemborexant
|
6.68 % unbound
Geometric Coefficient of Variation 10.4
|
7.11 % unbound
Geometric Coefficient of Variation 10.7
|
|
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
|
25.5 % unbound
Geometric Coefficient of Variation 6.90
|
|
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
|
8.63 % unbound
Geometric Coefficient of Variation 11.9
|
SECONDARY outcome
Timeframe: Day 1: predose, 0.5 up to 240 hours postdosePopulation: 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.
Unbound fraction of drug in plasma was calculated as 100% - mean percent of Lemborexant bound to plasma protein for each participant.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=7 Participants
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.
|
Lemborexant: Normal Renal Function
n=7 Participants
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.
|
|---|---|---|
|
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
|
309 liter per hour (L/h)
Geometric Coefficient of Variation 44.3
|
SECONDARY outcome
Timeframe: Up to Day 11Population: The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs
|
5 Participants
|
7 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 11Population: The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
Number of Participants With Clinically Significant Laboratory Abnormalities
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 11Population: The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormal Vital Sign Values
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 11Population: The safety analysis set was the group of participants who were dosed with the test drug and had at least one postdose safety assessment.
Outcome measures
| Measure |
Lemborexant: Severe Renal Impairment
n=8 Participants
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.
|
Lemborexant: Normal Renal Function
n=8 Participants
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.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Parameter Values
|
0 Participants
|
0 Participants
|
Adverse Events
Lemborexant: Severe Renal Impairment
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Lemborexant: Normal Renal Function
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Lemborexant: Severe Renal Impairment
n=8 participants at risk
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.
|
Lemborexant: Normal Renal Function
n=8 participants at risk
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.
|
|---|---|---|
|
General disorders
Chills
|
12.5%
1/8 • Up to Day 11
AEs were collected for the participants who were in the safety analysis set (all participants who were dosed with the test drug and had at least one postdose safety assessment).
|
0.00%
0/8 • Up to Day 11
AEs were collected for the participants who were in the safety analysis set (all participants who were dosed with the test drug and had at least one postdose safety assessment).
|
|
Nervous system disorders
Somnolence
|
62.5%
5/8 • Up to Day 11
AEs were collected for the participants who were in the safety analysis set (all participants who were dosed with the test drug and had at least one postdose safety assessment).
|
87.5%
7/8 • Up to Day 11
AEs were collected for the participants who were in the safety analysis set (all participants who were dosed with the test drug and had at least one postdose safety assessment).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place