Trial Outcomes & Findings for Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Mild and Moderate Hepatic Impairment Compared to Healthy Subjects (NCT NCT03440424)
NCT ID: NCT03440424
Last Updated: 2020-03-20
Results Overview
Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Plasma pharmacokinetic (PK) data were analyzed using a non-compartmental method of analysis.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Day 1: Predose, 0.5 up to 312 hours postdose
Results posted on
2020-03-20
Participant Flow
Participants took part in the study at 2 investigative sites in the United States from 26 January 2018 to 23 April 2018.
A total of 28 participants were screened, of which 4 were screen failures, and 24 were enrolled and received the study treatment.
Participant milestones
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 milligrams (mg) administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, body mass index \[BMI\]) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
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 Mild and Moderate Hepatic Impairment Compared to Healthy Subjects
Baseline characteristics by cohort
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57.0 years
STANDARD_DEVIATION 10.5 • n=99 Participants
|
61.4 years
STANDARD_DEVIATION 5.7 • n=107 Participants
|
56.8 years
STANDARD_DEVIATION 8.3 • n=206 Participants
|
58.4 years
STANDARD_DEVIATION 8.3 • n=157 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
7 Participants
n=157 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
17 Participants
n=157 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
12 Participants
n=157 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
12 Participants
n=157 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
24 Participants
n=157 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
PRIMARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Plasma pharmacokinetic (PK) data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
Cmax: Maximum Plasma Concentration of Lemborexant
|
62.9 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 34.9
|
48.7 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 37.7
|
39.8 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 31.1
|
PRIMARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-8 hours) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
AUC(0-8 Hours): Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Postdose of Lemoborexant
|
163 hour nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 32.8
|
138 hour nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 13.8
|
133 hour nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 25.1
|
PRIMARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-72 hours) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
AUC(0-72 Hours): Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Postdose of Lemoborexant
|
383 h*ng/mL
Geometric Coefficient of Variation 46.1
|
352 h*ng/mL
Geometric Coefficient of Variation 13.0
|
306 h*ng/mL
Geometric Coefficient of Variation 25.0
|
PRIMARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-t hours) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
AUC(0-t Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration of Lemborexant
|
574 h*ng/mL
Geometric Coefficient of Variation 50.7
|
651 h*ng/mL
Geometric Coefficient of Variation 25.6
|
435 h*ng/mL
Geometric Coefficient of Variation 33.2
|
PRIMARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter. Here "Overall number of participants analyzed" signifies the participants who were evaluable for this outcome measure.
Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-inf) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=7 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=6 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
AUC(0-inf): Area Under Plasma Concentration Versus Time Curve From Time Zero to Infinity of Lemborexant
|
567 h*ng/mL
Geometric Coefficient of Variation 52.0
|
696 h*ng/mL
Geometric Coefficient of Variation 34.6
|
453 h*ng/mL
Geometric Coefficient of Variation 33.9
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter. Here "Overall number of participants analyzed" signifies the participants who were evaluable 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). Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUCu was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=7 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=6 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Lemborexant
|
34.9 h*ng/mL
Geometric Coefficient of Variation 52.6
|
45.1 h*ng/mL
Geometric Coefficient of Variation 42.6
|
27.1 h*ng/mL
Geometric Coefficient of Variation 36.8
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Blood samples were analyzed for the amount of lemborexant's metabolites (M4, M9, M10) in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
Cmax: Maximum Plasma Concentration of Lemborexant's Metabolites M4, M9, and M10
M4
|
7.73 ng/mL
Geometric Coefficient of Variation 36.4
|
5.74 ng/mL
Geometric Coefficient of Variation 46.7
|
7.97 ng/mL
Geometric Coefficient of Variation 33.0
|
|
Cmax: Maximum Plasma Concentration of Lemborexant's Metabolites M4, M9, and M10
M9
|
4.49 ng/mL
Geometric Coefficient of Variation 45.1
|
3.50 ng/mL
Geometric Coefficient of Variation 46.4
|
5.33 ng/mL
Geometric Coefficient of Variation 28.9
|
|
Cmax: Maximum Plasma Concentration of Lemborexant's Metabolites M4, M9, and M10
M10
|
3.52 ng/mL
Geometric Coefficient of Variation 44.4
|
2.84 ng/mL
Geometric Coefficient of Variation 38.4
|
3.71 ng/mL
Geometric Coefficient of Variation 34.8
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Blood samples were analyzed for the amount of lemborexant and its metabolites (M4, M9, M10) in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
Tmax: Time to Reach Maximum Plasma Concentration of Lemborexant and Its Metabolites M4, M9, M10
Lemborexant
|
1.00 hours
Interval 0.5 to 1.5
|
1.00 hours
Interval 0.5 to 3.0
|
1.25 hours
Interval 0.5 to 4.0
|
|
Tmax: Time to Reach Maximum Plasma Concentration of Lemborexant and Its Metabolites M4, M9, M10
M4
|
1.75 hours
Interval 1.0 to 4.0
|
1.75 hours
Interval 1.0 to 4.0
|
2.00 hours
Interval 1.0 to 4.0
|
|
Tmax: Time to Reach Maximum Plasma Concentration of Lemborexant and Its Metabolites M4, M9, M10
M9
|
1.25 hours
Interval 1.0 to 3.0
|
1.25 hours
Interval 1.0 to 4.0
|
1.50 hours
Interval 1.0 to 4.0
|
|
Tmax: Time to Reach Maximum Plasma Concentration of Lemborexant and Its Metabolites M4, M9, M10
M10
|
4.00 hours
Interval 2.0 to 24.0
|
3.00 hours
Interval 1.0 to 4.0
|
4.00 hours
Interval 4.0 to 24.0
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Blood samples were analyzed for the amount of lemborexant's metabolites (M4, M9, M10) in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-8 hours) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
AUC(0-8 Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to 8 Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M4
|
44.2 h*ng/mL
Geometric Coefficient of Variation 27.2
|
31.0 h*ng/mL
Geometric Coefficient of Variation 34.4
|
44.6 h*ng/mL
Geometric Coefficient of Variation 28.6
|
|
AUC(0-8 Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to 8 Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M9
|
17.5 h*ng/mL
Geometric Coefficient of Variation 29.2
|
14.0 h*ng/mL
Geometric Coefficient of Variation 31.1
|
22.2 h*ng/mL
Geometric Coefficient of Variation 19.3
|
|
AUC(0-8 Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to 8 Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M10
|
21.4 h*ng/mL
Geometric Coefficient of Variation 40.7
|
16.3 h*ng/mL
Geometric Coefficient of Variation 35.1
|
22.6 h*ng/mL
Geometric Coefficient of Variation 40.4
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Blood samples were analyzed for the amount of lemborexant's metabolites (M4, M9, M10) in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-72 hours) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
AUC(0-72 Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to 72 Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M4
|
153 h*ng/mL
Geometric Coefficient of Variation 36.7
|
123 h*ng/mL
Geometric Coefficient of Variation 19.5
|
144 h*ng/mL
Geometric Coefficient of Variation 26.8
|
|
AUC(0-72 Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to 72 Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M9
|
52.1 h*ng/mL
Geometric Coefficient of Variation 29.1
|
52.5 h*ng/mL
Geometric Coefficient of Variation 18.9
|
69.1 h*ng/mL
Geometric Coefficient of Variation 18.0
|
|
AUC(0-72 Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to 72 Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M10
|
167 h*ng/mL
Geometric Coefficient of Variation 41.3
|
130 h*ng/mL
Geometric Coefficient of Variation 23.0
|
175 h*ng/mL
Geometric Coefficient of Variation 35.3
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Blood samples were analyzed for the amount of lemborexant's metabolites (M4, M9, M10) in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-t hours) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
AUC(0-t Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to t Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M4
|
208 h*ng/mL
Geometric Coefficient of Variation 45.8
|
191 h*ng/mL
Geometric Coefficient of Variation 20.6
|
184 h*ng/mL
Geometric Coefficient of Variation 31.3
|
|
AUC(0-t Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to t Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M9
|
69.7 h*ng/mL
Geometric Coefficient of Variation 34.9
|
89.6 h*ng/mL
Geometric Coefficient of Variation 23.0
|
88.7 h*ng/mL
Geometric Coefficient of Variation 21.4
|
|
AUC(0-t Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to t Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M10
|
334 h*ng/mL
Geometric Coefficient of Variation 42.8
|
321 h*ng/mL
Geometric Coefficient of Variation 19.9
|
305 h*ng/mL
Geometric Coefficient of Variation 41.5
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter. Here "Number analyzed" signifies participants who were evaluable for this outcome measure for different metabolites M4, M9, and M10.
Blood samples were analyzed for the amount of lemborexant's metabolites (M4, M9, M10) in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. AUC(0-inf) was calculated by the linear-up log-down trapezoidal method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
AUC(0-inf): Area Under Plasma Concentration Versus Time Curve From Time Zero to Inf Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M4
|
220 h*ng/mL
Geometric Coefficient of Variation 50.3
|
223 h*ng/mL
Geometric Coefficient of Variation 21.3
|
191 h*ng/mL
Geometric Coefficient of Variation 31.6
|
|
AUC(0-inf): Area Under Plasma Concentration Versus Time Curve From Time Zero to Inf Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M9
|
72.6 h*ng/mL
Geometric Coefficient of Variation 34.7
|
108 h*ng/mL
Geometric Coefficient of Variation 21.6
|
92.5 h*ng/mL
Geometric Coefficient of Variation 23.5
|
|
AUC(0-inf): Area Under Plasma Concentration Versus Time Curve From Time Zero to Inf Hours Postdose of Lemborexant's Metabolites M4, M9, and M10
M10
|
304 h*ng/mL
Geometric Coefficient of Variation 27.7
|
332 h*ng/mL
Geometric Coefficient of Variation 17.9
|
320 h*ng/mL
Geometric Coefficient of Variation 41.9
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter. Here "Number analyzed" signifies participants who were evaluable for this outcome measure for 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. Blood samples were analyzed for the amount of lemborexant and its metabolites (M4, M9, M10) in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
T1/2: Terminal Plasma Phase Half-life of Lemborexant and Its Metabolites M4, M9, M10
M10
|
71.0 hrs
Interval 40.3 to 88.9
|
96.8 hrs
Interval 67.4 to 118.0
|
69.3 hrs
Interval 32.3 to 90.7
|
|
T1/2: Terminal Plasma Phase Half-life of Lemborexant and Its Metabolites M4, M9, M10
Lemborexant
|
92.7 hrs
Interval 33.4 to 104.0
|
115 hrs
Interval 72.8 to 144.0
|
71.1 hrs
Interval 40.4 to 88.9
|
|
T1/2: Terminal Plasma Phase Half-life of Lemborexant and Its Metabolites M4, M9, M10
M4
|
69.2 hrs
Interval 26.7 to 95.1
|
102 hrs
Interval 75.6 to 112.0
|
68.1 hrs
Interval 16.7 to 95.3
|
|
T1/2: Terminal Plasma Phase Half-life of Lemborexant and Its Metabolites M4, M9, M10
M9
|
49.0 hrs
Interval 26.4 to 102.0
|
88.4 hrs
Interval 70.0 to 126.0
|
49.7 hrs
Interval 14.0 to 72.7
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
CL/F is the clearance for parent lemborexant only and was calculated as Dose/\[AUC 0-inf\]. Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=7 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=6 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
CL/F: Apparent Total Body Clearance of Lemborexant
|
17.6 Liter per hour (L/hr)
Geometric Coefficient of Variation 52.0
|
14.4 Liter per hour (L/hr)
Geometric Coefficient of Variation 34.6
|
22.1 Liter per hour (L/hr)
Geometric Coefficient of Variation 33.9
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
The apparent volume of distribution gives information about amount of lemborexant distributed in body tissue rather than the blood/plasma. Vz/F for parent lemborexant only was calculated as Dose/(AUC0-inf multiplied by elimination rate constant\[λz\]). Area under the plasma concentration-time curve from time zero to infinity, calculated(AUC0-inf) as AUC0-t + AUCextra. AUCextra represents an extrapolated value obtained by Clast/λz, where Clast: plasma concentration at last sampling time point at which measured plasma concentration is at or above LLQ. λz is the elimination rate constant. Elimination rate constant obtained from linear regression of terminal phase of log transformed concentration-time data. A minimum of three points is required to calculate λz. Blood samples were analyzed for amount of lemborexant in plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=7 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=6 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
Vz/F: Apparent Volume of Distribution of Lemborexant
|
1880 Liter (L)
Geometric Coefficient of Variation 72.7
|
2170 Liter (L)
Geometric Coefficient of Variation 13.5
|
2130 Liter (L)
Geometric Coefficient of Variation 30.1
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter. Here "Number analyzed" signifies participants who were evaluable for the outcome measure for each metabolite (M4, M9, and M10).
The MPR is the ratio of AUC(0-inf) of the individual lemborexant metabolites (M4, M9, M10) to AUC(0-inf) of lemborexant, corrected for molecular weights. Blood samples were analyzed for the amount of lemborexant metabolites in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
MPR: Metabolite-to-Parent Ratios of AUC(0-inf) for Lemborexant's Metabolites M4, M9, and M10
M4
|
0.343 ratio
Geometric Coefficient of Variation 2.90
|
0.289 ratio
Geometric Coefficient of Variation 23.4
|
0.405 ratio
Geometric Coefficient of Variation 11.5
|
|
MPR: Metabolite-to-Parent Ratios of AUC(0-inf) for Lemborexant's Metabolites M4, M9, and M10
M9
|
0.123 ratio
Geometric Coefficient of Variation 19.0
|
0.144 ratio
Geometric Coefficient of Variation 17.4
|
0.198 ratio
Geometric Coefficient of Variation 22.0
|
|
MPR: Metabolite-to-Parent Ratios of AUC(0-inf) for Lemborexant's Metabolites M4, M9, and M10
M10
|
0.600 ratio
Geometric Coefficient of Variation 15.3
|
0.502 ratio
Geometric Coefficient of Variation 20.4
|
0.680 ratio
Geometric Coefficient of Variation 18.9
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter.
Unbound fraction of drug in plasma was calculated as 100 percent (%) - mean percent of lemborexant and its metabolites M4, M9, and M10 bound to plasma protein for each participant. Blood samples were analyzed for the amount of lemborexant and its metabolites (M4, M9, M10) in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
fu: Plasma Protein Unbound Fraction of Lemborexant and Its Metabolites M4, M9, and M10
M10
|
0.0765 % (percent) unbound
Geometric Coefficient of Variation 15.4
|
0.0754 % (percent) unbound
Geometric Coefficient of Variation 16.6
|
0.0669 % (percent) unbound
Geometric Coefficient of Variation 20.2
|
|
fu: Plasma Protein Unbound Fraction of Lemborexant and Its Metabolites M4, M9, and M10
Lemborexant
|
0.0630 % (percent) unbound
Geometric Coefficient of Variation 14.2
|
0.0650 % (percent) unbound
Geometric Coefficient of Variation 11.4
|
0.0597 % (percent) unbound
Geometric Coefficient of Variation 15.3
|
|
fu: Plasma Protein Unbound Fraction of Lemborexant and Its Metabolites M4, M9, and M10
M4
|
0.247 % (percent) unbound
Geometric Coefficient of Variation 7.77
|
0.247 % (percent) unbound
Geometric Coefficient of Variation 12.4
|
0.230 % (percent) unbound
Geometric Coefficient of Variation 12.8
|
|
fu: Plasma Protein Unbound Fraction of Lemborexant and Its Metabolites M4, M9, and M10
M9
|
0.146 % (percent) unbound
Geometric Coefficient of Variation 14.0
|
0.142 % (percent) unbound
Geometric Coefficient of Variation 9.61
|
0.136 % (percent) unbound
Geometric Coefficient of Variation 15.8
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5 up to 312 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 1 PK parameter. Here "Overall number of participants analyzed" signifies participants who were evaluable 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. Blood samples were analyzed for the amount of lemborexant in the plasma. Plasma concentration-time data were measured by validated LC-MS/MS method. Plasma PK data were analyzed using a non-compartmental method of analysis.
Outcome measures
| Measure |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=7 Participants
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=6 Participants
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 Participants
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration Based on AUCu of Lemborexant
|
287 L/h
Geometric Coefficient of Variation 52.6
|
222 L/h
Geometric Coefficient of Variation 42.6
|
370 L/h
Geometric Coefficient of Variation 36.8
|
Adverse Events
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort C: Healthy Participants (Control)
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 |
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
n=8 participants at risk
Participants with mild hepatic impairment (Child-Pugh Class A, score 5 to 6) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
n=8 participants at risk
Participants with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period. The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis.
|
Cohort C: Healthy Participants (Control)
n=8 participants at risk
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (with regards to age, sex, BMI) received lemborexant 10 mg administered as a tablet, orally in the morning on Day 1 of the 14-day Treatment Period.
|
|---|---|---|---|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
12.5%
1/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
0.00%
0/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
|
General disorders
Chills
|
0.00%
0/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
12.5%
1/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
0.00%
0/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
|
Nervous system disorders
Headache
|
0.00%
0/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
12.5%
1/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
0.00%
0/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
|
Nervous system disorders
Somnolence
|
87.5%
7/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
62.5%
5/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
87.5%
7/8 • From the date of first dose up to 28 days after the last dose of study drug (up to 42 days)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place