Hepatic ImpairmentPhase 1NCT03440424
Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Mild and Moderate Hepatic Impairment Compared to Healthy Subjects
A Phase 1 study testing Lemborexant in people with Hepatic Impairment, run by Eisai Inc. at 2 sites in United States.
Trial summary
This study will be conducted to assess the effect of mild and moderate hepatic impairment on the pharmacokinetics (PK) of lemborexant after a single-dose administration. Read more about this study
- Who is it for?
- Ages 18 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- Lemborexant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Jan 2018to 23 Apr 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female participants, ages 18 to 79, inclusive, at the time of informed consent
- Body Mass Index (BMI) between 18 and 40 kilograms per meters squared, inclusive, at Screening
- Voluntary agreement to provide written informed consent, and the willingness and ability to comply with all aspects of the protocol
- Nonsmokers or smokers who smoke 20 cigarettes or less per day
- For Cohorts A and B: stable (without any change in disease status for at least 60 days prior to study Screening) hepatic impairment conforming to Child-Pugh classification A or B, respectively, and documented by medical history and a physical examination
- For Cohort C: healthy participants matched to participants with hepatic impairment with regard to age (±10 years), sex, and BMI (±20%), and as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiogram (ECG), and clinical laboratory determinations
Who cannot join
- Females who are breastfeeding or pregnant at Screening or Baseline
- Females of childbearing potential who did not use a highly effective method of contraception within 28 days before study entry, or who did not agree to use an approved method of contraception from 28 days before study entry, throughout the entire study period, and for 28 days after study drug discontinuation. Approved (highly effective) methods of contraception for this study included at least one of the following: 1. Total abstinence (if it was their preferred and usual lifestyle); 2. An intrauterine device or intrauterine hormone-releasing system (IUS); 3. A double-barrier method of contraception such as condom plus diaphragm with spermicide; 4. A contraceptive implant; 5. An oral contraceptive (with additional barrier method). Participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing, throughout the study, and for 28 days after study drug discontinuation; 6. Have a vasectomized partner with confirmed azoospermia. (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 (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
- Known to be positive for human immunodeficiency virus
- Currently enrolled in another clinical study or used any investigational drug or device within 4 weeks, or 5 times the half-life of the investigational drug (whichever is longer), preceding informed consent
- Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing until study discharge
- Intake of herbal preparations containing St. John's Wort within 4 weeks prior to dosing until study discharge
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- Intake of nutritional supplements (including herbal preparations), foods or beverages that may affect cytochrome P3A enzyme (e.g., alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [e.g., kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard] and charbroiled meats) within 1 week before dosing until study discharge
- Intake of beverages, food, or other products that contain caffeine from 24 hours before until 48 hours after dosing with lemborexant
- Engagement in strenuous exercise (e.g., moving large bulky items, bodybuilding) within 2 weeks prior to check-in until study discharge
- History of clinically significant drug or food allergies, or is presently experiencing significant seasonal allergies
- A prolonged QT/corrected QT (QTc) interval (QTc >480 milliseconds) demonstrated on ECG at Screening or Baseline (Day -1)
- Any major surgery within 4 weeks of study drug administration
- Any history of abdominal surgery that may affect pharmacokinetics of lemborexant (e.g., hepatectomy, nephrectomy, digestive organ resection)
- Inability to tolerate oral medication
- Inability to tolerate venous access and/or venipuncture
- Unwilling to abide by the study requirements, or in the opinion of the investigator, is not likely to complete the study
- Additional Exclusion Criteria for Hepatically Impaired Participants (Cohorts A and B):
- In addition to the Exclusion Criteria listed above for all participants, other standard exclusion criteria for participants with hepatic impairment will be used. These include:
- Any significant acute medical illness (such as new conditions or exacerbation of pre-existing conditions) within 8 weeks of dosing
- Medical conditions which are not adequately and stably controlled on stable doses of medications or which, in the clinical opinion of the Principal Investigator, may interfere with study procedures or participant safety within 4 weeks before dosing (e.g., psychiatric disorders and disorders of the gastrointestinal tract, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism)
- History of esophageal and gastric variceal bleeding within the past 6 months unless the participant has completed a course of endoscopic therapy with the appropriate documentation (e.g., endoscopy report) of successful ablation of esophageal varices; participants with esophageal varices may be included if not bleeding within the past 6 months or have been treated adequately by ablation therapy, as specified above.
- Spontaneous bacterial peritonitis within 3 months of dosing
- Treatment with plasmapheresis within 6 months of dosing
- Primarily cholestatic liver diseases (e.g., primary biliary cirrhosis or primary sclerosing cholangitis)
- Current or recent (within 3 months prior to Screening) history of significant gastrointestinal disease other than that secondary to hepatic impairment
- Autoimmune liver disease
- Active alcoholic hepatitis determined either clinically or by histology
- History of hepatoma or metastatic disease of the liver
- Presence of severe ascites or edema
- Presence of hepatopulmonary syndrome or hydrothorax, or hepatorenal syndrome
- Known significant bleeding diathesis that could preclude multiple venipunctures (international normalization ratio >2.5)
- Creatinine clearance <60 milliliters per minute at Screening or Baseline as calculated using Cockroft and Gault Equation
- The participant's standard therapy/concomitant medication for diseases related to cirrhosis has not remained stable/unchanged for at least 14 days before the first dose of study drug
- History of drug or alcohol dependency or abuse within 4 weeks prior to Screening, or those who have a positive urine drug test or breath alcohol test at Screening or Baseline unless a prescribed medication for the underlying condition is the cause of the positive urine screen
- Additional Exclusion Criteria for Healthy Participants (Cohort C):
- In addition to the Exclusion Criteria listed above for all participants, other standard exclusion criteria for healthy participants in Phase 1 studies will be used. These include:
- Presence of active liver disease, or acute liver injury, as indicated by (1) an abnormal liver function test, or (2) clinical or laboratory signs of active viral hepatitis (including B and C, as demonstrated by positive serology at Screening)
- Clinically significant illness, within 4 weeks prior to dosing, that requires medical treatment or may influence the outcome of the study; e.g., 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 abnormal finding based on physical examination, assessment of vital signs, ECG, or laboratory test results that require treatment or clinical follow-up based on the investigator's opinion
- History of drug or alcohol use disorder within the 2 years prior to Screening, or those who have a positive urine drug test or breathalyzer alcohol test at Screening or Baseline
- Use of any prescription drugs within 4 weeks prior to dosing until study discharge
- Intake of any over-the-counter medications within 2 weeks prior to dosing until study discharge
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Clinical Pharmacology of Miami, LLC
Miami, Florida, 33014
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
Official title: An Open-Label, Parallel-Group Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Mild and Moderate Hepatic Impairment Compared to Healthy Subjects
This study will be conducted to assess the effect of mild and moderate hepatic impairment on the pharmacokinetics (PK) of lemborexant after a single-dose administration.
- Conditions
- Hepatic Impairment
- Being tested
- Lemborexant
- Keywords
- mild hepatic impairment, moderate hepatic impairment, lemborexant, healthy participants, metabolites, E2006, pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LemborexantDrug
oral tablet
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Mild Hepatic Impairment (Child Pugh Class A) | Experimental | Participants with mild hepatic impairment will receive a single 10 milligram (mg) dose (1 × 10 mg lemborexant [E2006] tablet) in the morning with 240 milliliters (mL) of water following an overnight fast of at least 10 hours. Receives: Drug: Lemborexant |
| Cohort B: Moderate Hepatic Impairment (Child Pugh Class B) | Experimental | Participants with moderate hepatic impairment will receive a single 10 mg dose (1 × 10 mg lemborexant [E2006] tablet) in the morning with 240 mL of water following an overnight fast of at least 10 hours. Receives: Drug: Lemborexant |
| Cohort C: Healthy Participants (Control) | Experimental | Healthy participants matched to participants with hepatic impairment in Cohorts A and B (matched with regards to age, sex, body mass index [BMI]) will receive a single 10 mg dose (1 × 10 mg lemborexant [E2006] tablet) in the morning with 240 mL of water following an overnight fast of at least 10 hours. Receives: Drug: Lemborexant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax: Maximum Plasma Concentration of Lemborexant
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
AUC(0-8 Hours): Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Postdose of Lemoborexant
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
AUC(0-72 Hours): Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Postdose of Lemoborexant
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
AUC(0-t Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration of Lemborexant
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
AUC(0-inf): Area Under Plasma Concentration Versus Time Curve From Time Zero to Infinity of Lemborexant
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
Secondary outcomes (13)
AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Lemborexant
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
Cmax: Maximum Plasma Concentration of Lemborexant's 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. Plasma PK data were analyzed using a non-compartmental method of analysis.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
Tmax: Time to Reach Maximum Plasma Concentration of Lemborexant and Its Metabolites M4, M9, M10
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
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
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
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
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
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
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
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
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
T1/2: Terminal Plasma Phase Half-life of Lemborexant and Its Metabolites M4, M9, 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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
CL/F: Apparent Total Body Clearance of Lemborexant
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
Vz/F: Apparent Volume of Distribution of Lemborexant
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
MPR: Metabolite-to-Parent Ratios of AUC(0-inf) for Lemborexant's Metabolites 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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
fu: Plasma Protein Unbound Fraction of Lemborexant and Its Metabolites M4, M9, and M10
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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration Based on AUCu of Lemborexant
Unbound fraction of drug in plasma was calculated as 100% - mean percent of lemborexant bound to plasma protein for each participant. 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.
Measured: Day 1: Predose, 0.5 up to 312 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2018
- Study start26 Jan 2018
- Primary completion23 Apr 2018
- Study completion23 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Purdue Pharma LP
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03440424
- Sponsor's protocol ID
- E2006-A001-104
- Status last verified
- Feb 2018
- First submitted
- 14 Feb 2018
- Last updated
- 20 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Parallel-Group Study to Evaluate the Pharmacokinetics of Lemborexant (E2006) and Its Metabolites in Subjects With Mild and Moderate Hepatic Impairment Compared to Healthy Subjects
- ClinicalTrials.gov ID
- NCT03440424
- Acronym / sponsor ID
- E2006-A001-104
- Conditions
- Hepatic Impairment
- Keywords
- mild hepatic impairment, moderate hepatic impairment, lemborexant, healthy participants, metabolites, E2006, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Collaborators
- Purdue Pharma LP
- Study start
- 26 Jan 2018 (actual)
- Primary completion
- 23 Apr 2018 (actual)
- Study completion
- 23 Apr 2018 (actual)
- First posted
- 22 Feb 2018 (actual)
- Results
- Posted 18 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be conducted to assess the effect of mild and moderate hepatic impairment on the pharmacokinetics (PK) of lemborexant after a single-dose administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Mild Hepatic Impairment (Child Pugh Class A) | Experimental | Drug: LemborexantParticipants with mild hepatic impairment will receive a single 10 milligram (mg) dose (1 × 10 mg lemborexant [E2006] tablet) in the morning with 240 milliliters (mL) of water following an overnight fast of at least 10 hours. |
| Cohort B: Moderate Hepatic Impairment (Child Pugh Class B) | Experimental | Drug: LemborexantParticipants with moderate hepatic impairment will receive a single 10 mg dose (1 × 10 mg lemborexant [E2006] tablet) in the morning with 240 mL of water following an overnight fast of at least 10 hours. |
| Cohort C: Healthy Participants (Control) | Experimental | Drug: LemborexantHealthy participants matched to participants with hepatic impairment in Cohorts A and B (matched with regards to age, sex, body mass index [BMI]) will receive a single 10 mg dose (1 × 10 mg lemborexant [E2006] tablet) in the morning with 240 mL of water following an overnight fast of at least 10 hours. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female participants, ages 18 to 79, inclusive, at the time of informed consent
- Body Mass Index (BMI) between 18 and 40 kilograms per meters squared, inclusive, at Screening
- Voluntary agreement to provide written informed consent, and the willingness and ability to comply with all aspects of the protocol
- Nonsmokers or smokers who smoke 20 cigarettes or less per day
- For Cohorts A and B: stable (without any change in disease status for at least 60 days prior to study Screening) hepatic impairment conforming to Child-Pugh classification A or B, respectively, and documented by medical history and a physical examination
Key exclusion criteria (42 listed)
- Females who are breastfeeding or pregnant at Screening or Baseline
- Females of childbearing potential who did not use a highly effective method of contraception within 28 days before study entry, or who did not agree to use an approved method of contraception from 28 days before study entry, throughout the entire study period, and for 28 days after study drug discontinuation. Approved (highly effective) methods of contraception for this study included at least one of the following: 1. Total abstinence (if it was their preferred and usual lifestyle); 2. An intrauterine device or intrauterine hormone-releasing system (IUS); 3. A double-barrier method of contraception such as condom plus diaphragm with spermicide; 4. A contraceptive implant; 5. An oral contraceptive (with additional barrier method). Participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing, throughout the study, and for 28 days after study drug discontinuation; 6. Have a vasectomized partner with confirmed azoospermia. (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 (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
- Known to be positive for human immunodeficiency virus
- Currently enrolled in another clinical study or used any investigational drug or device within 4 weeks, or 5 times the half-life of the investigational drug (whichever is longer), preceding informed consent
- Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing until study discharge
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lemborexantoral tablet | Drug | Cohort A: Mild Hepatic Impairment (Child Pugh Class A), Cohort B: Moderate Hepatic Impairment (Child Pugh Class B), Cohort C: Healthy Participants (Control) |
Primary outcome
Cmax: Maximum Plasma Concentration of Lemborexant
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
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.
AUC(0-8 Hours): Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Postdose of Lemoborexant
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
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.
AUC(0-72 Hours): Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours Postdose of Lemoborexant
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
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.
AUC(0-t Hours): Area Under Plasma Concentration Versus Time Curve From Time Zero to Time of Last Quantifiable Concentration of Lemborexant
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
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.
AUC(0-inf): Area Under Plasma Concentration Versus Time Curve From Time Zero to Infinity of Lemborexant
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
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.
13 secondary outcomes
AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Lemborexant
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
Cmax: Maximum Plasma Concentration of Lemborexant's Metabolites M4, M9, and M10
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
Tmax: Time to Reach Maximum Plasma Concentration of Lemborexant and Its Metabolites M4, M9, M10
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
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
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
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
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
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
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
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
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
T1/2: Terminal Plasma Phase Half-life of Lemborexant and Its Metabolites M4, M9, M10
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
CL/F: Apparent Total Body Clearance of Lemborexant
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
Vz/F: Apparent Volume of Distribution of Lemborexant
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
MPR: Metabolite-to-Parent Ratios of AUC(0-inf) for Lemborexant's Metabolites M4, M9, and M10
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
fu: Plasma Protein Unbound Fraction of Lemborexant and Its Metabolites M4, M9, and M10
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration Based on AUCu of Lemborexant
Time frame: Day 1: Predose, 0.5 up to 312 hours postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lemborexant in people with Hepatic Impairment, run by Eisai Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax: Maximum Plasma Concentration of Lemborexant (time frame: Day 1: Predose, 0.5 up to 312 hours postdose). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2020.