A Single and Multiple Dose Study of Lemborexant in Healthy Chinese Participants

NCT04555733 | Completed Phase 1

• 1 other identifier: E2006-J086-014
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess the pharmacokinetics (PK) of lemborexant and metabolites (M4, M9, and M10) in plasma in healthy Chinese participants following single and multiple oral doses of lemborexant.

Conditions

Healthy Volunteer

Keywords

Pharmacokinetics; Phase 1; E2006; Healthy Participants

Outcome Measures

Primary Outcomes (30)

• Cmax: Maximum Observed Plasma Concentration for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• AUC(0-8h): Area Under the Concentration-time Curve From Zero Time to 8 Hours Postdose for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-8 hours post single dose

• AUC(0-24h): Area Under the Concentration-time Curve From Zero Time to 24 Hours Postdose for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-24 hours post single dose

• AUC(0-t): Area Under the Concentration-time Curve From Zero Time to Time of Last Quantifiable Concentration for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• AUC(0-inf): Area Under the Concentration-time Curve From Zero Time Extrapolated to Infinite Time for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• λz: Terminal Phase Rate Constant for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• t½: Terminal Elimination Phase Half-life for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• MRT: Mean Residence Time for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• Vz/F: Apparent Volume of Distribution at Terminal Phase for Lemborexant Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• CL/F: Apparent Total Clearance Following Extravascular Administration for Lemborexant Following Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• Metabolite to Lemborexant Area Under the Concentration-time Curve From Zero Time Extrapolated to Infinite Time Ratio Following Molecular Weight Correction to Lemborexant Equivalents After Single Dose in All Cohorts

  All Cohorts, Day 1: 0-240 hours post single dose

• Cmax: Maximum Observed Plasma Concentration for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose (Day 15 dosing) in Cohort 2

  Cohort 2, Day 15: 0-24 hours post single dose

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose (Day 15 dosing) in Cohort 2

  Cohort 2, Day 15: 0-24 hours post single dose

• AUC(0-8h): Area Under the Concentration-time Curve From Zero Time to 8 Hours Postdose for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose (Day 15 dosing) in Cohort 2

  Cohort 2, Day 15: 0-8 hours post single dose

• AUC(0-24h): Area Under the Concentration-time Curve From Zero Time to 24 Hours Postdose for Lemborexant and Its Metabolites (M4, M9, and M10) Following Single Dose (Day 15 dosing) in Cohort 2

  Cohort 2, Day 15: 0-24 hours post single dose

• AUC(0-8h): Area Under the Concentration-time Curve From Zero Time to 8 Hours Postdose for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses (Day 28 dosing) in Cohort 2

  Cohort 2, Day 28: 0-8 hours post multiple dose

• AUC(0-τ): Area Under the Concentration-time Curve Over the Dosing Interval for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• Css,avg: Average Steady State Concentration for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• Css,max: Maximum Observed Concentration at Steady State for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• Css,min: Minimum Observed Concentration at Steady State for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• PTF: Peak-trough Fluctuation for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• Tss,max: Time to Reach the Maximum Plasma Concentration (Cmax) for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses at Steady State in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• λz: Terminal Phase Rate Constant for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• t½: Terminal Elimination Phase Half-life for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• MRT: Mean Residence Time for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• Vz/F: Apparent Volume of Distribution at Terminal Phase for Lemborexant Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• CLss/F: Apparent Total Clearance Following Extravascular Administration at Steady-state for Lemborexant Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• Rac: Accumulation Ratio for Lemborexant and Its Metabolites (M4, M9, and M10) Following Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

• Metabolite to Lemborexant Area Under the Concentration-time Curve Over the Dosing Interval Ratio Following Molecular Weight Correction to Lemborexant Equivalents After Multiple Doses in Cohort 2

  Cohort 2, Day 28: 0-324 hours post multiple dose

Study Arms (3)

Cohort 1: Lemborexant 5 mg

EXPERIMENTAL

Participants will receive a single dose of lemborexant 5 milligram (mg) tablet, orally on Day 1.

Drug: Lemborexant

Cohort 2: Lemborexant 10 mg

EXPERIMENTAL

Participants will receive a single dose of lemborexant 10 mg tablet, orally on Day 1 followed by a washout period of approximately 14 days further followed by multiple doses of lemborexant 10 mg tablets, orally, once daily from Day 15 through Day 28.

Drug: Lemborexant

Cohort 3: Lemborexant 25 mg

EXPERIMENTAL

Participants will receive a single dose of lemborexant 25 mg (1\*5 mg tablet and 2\*10 mg tablet), orally on Day 1.

Drug: Lemborexant

Interventions

Lemborexant DRUG

Lemborexant oral tablets.

Also known as: E2006, Dayvigo

Cohort 1: Lemborexant 5 mg; Cohort 2: Lemborexant 10 mg; Cohort 3: Lemborexant 25 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Chinese adult male or female participants living in China.
• Non-smoking, age greater than or equal to (\>=) 18 years and less than or equal to (\<=) 45 years old at the time of obtaining written consent. To be considered non-smokers, participant must have discontinued smoking for at least 4 weeks before first dosing.
• Participants with a body mass index (BMI) of 19 to 24 kilogram per square meter (kg/m\^2) at screening.

You may not qualify if:

• Participants who weigh less than 50 kilogram (kg) at Screening.
• Females who are breastfeeding or pregnant (as documented by a positive beta-human chorionic gonadotropin \[β-hCG\] test with a minimum sensitivity of International units per liter (IU/L) or equivalent units of β-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
• Females of childbearing potential who:
• a. Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
• i. total abstinence (if it is their preferred and usual lifestyle)
• ii. an intrauterine device or intrauterine hormone-releasing system (IUS)
• iii. a contraceptive implant
• iv. an oral contraceptive except for contraceptives containing levonorgestrel (with additional barrier method) (Participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation.)
• v. have a vasectomized partner with confirmed azoospermia.
• b. Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation.
• It is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, that is, double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide.
• NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
• Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks before first dosing.
• Evidence of disease that may influence the outcome of the study within 4 weeks before first dosing; example psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism.
• Any suicidal ideation with intent to act with or without a plan at screening or within 6 months of screening.

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (1)

Xuhui Central Hospital

Shanghai, China

Location

MeSH Terms

Interventions

lemborexant

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 21, 2020
• Study Start: October 26, 2020
• Primary Completion: January 13, 2021
• Study Completion: January 13, 2021
• Last Updated: July 19, 2021

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)