Clinical trial NCT03483636: Study of Lemborexant-Alcohol Interaction in Healthy Subjects
Official title: Single-Center, Double-Blind, Placebo-Controlled, Single-Dose, 4-Period Crossover, Drug-Alcohol Interaction Study in Lemborexant in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Drug-alcohol interaction
Lemborexant
E2006
Postural stability
Cognitive performance
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Purdue Pharma LP
First posted: 2018-03-30
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study will be conducted to evaluate the effects on cognitive performance (Power of Attention domain) and postural stability of lemborexant in combination with alcohol versus lemborexant alone and versus alcohol alone in healthy participants. This study will also assess the safety and tolerability of a single oral dose of lemborexant when administered alone or in combination with alcohol in healthy participants.


Eligibility criteria: Inclusion Criteria:

Participants must meet all of the following criteria to be included in this study:

* Healthy male or female, 19 to 55 years of age, inclusive, at the time of informed consent.
* Body mass index ≥22 kilograms per meters squared (kg/m\^2) and ≤33 kg/m\^2 and a minimum weight of 55.0 kilogram (kg) at Screening
* Current alcohol users who are occasional or regular drinkers, operationally defined as consuming at least 2 alcoholic beverages per week but not more than 2 alcoholic beverages per day in an average week, in the 6 months before Screening. This would result in consumption of 2 to 14 standard drinks per week, on average; 1 standard drink is equivalent to 43 mL (1.5 ounce \[oz.\]) of spirits (≥20% alcohol by volume), 142 mL (5 oz.) of wine, or 341 mL (12 oz.) of beer.
* Able to speak, read, and understand English sufficiently to allow completion of all study assessments.
* Provide written informed consent.

Exclusion Criteria:

Participants who meet any of the following criteria will be excluded from this study:

* Females who are breastfeeding or pregnant.
* Females of childbearing potential. 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).
* History of moderate or severe alcohol use disorder within the past 2 years (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), and/or participated in, is currently participating in, or is seeking treatment for substance and/or alcohol-related disorders (excluding nicotine and caffeine).
* Presence of insomnia, narcolepsy, obstructive sleep apnea, or restless legs syndrome or an exclusionary score on either of the following subscales of the SLEEP50 questionnaire:

  1. ≥15 on Apnea subscales
  2. ≥7 on Narcolepsy subscale.
* Current or prior diagnosis of any condition for which alcohol consumption is contraindicated (e.g., hypertriglyceridemia, pancreatitis, liver disease, porphyria, or congestive heart failure, judged as clinically relevant by the investigator).
* Evidence of disease that may influence the outcome of the study within 4 weeks prior to the first dose of study drug (e.g., congenital abnormality in metabolism, psychiatric disorders, and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system).
* Has been diagnosed with cancer within the 5 years before Screening (excluding squamous or basal cell carcinoma of the skin), or has an active malignancy of any type (including squamous or basal cell carcinoma of the skin).
* Known history of clinically significant drug allergy at Screening.
* Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening.
* Heavy smokers (≥20 cigarettes per day on average in the past 30 days prior to Screening), chews tobacco, uses a nicotine transdermal patch (including nicotine-containing products) or electronic cigarettes, and/or is unable to abstain from smoking for at least 10 hours during any day.
* Any clinically abnormal symptom or organ impairment found by reviewing medical history at Screening, physical examinations, vital signs, electrocardiogram finding (e.g., a prolonged corrected QT \[QTc\] interval \>450 milliseconds \[ms\]), or laboratory test results at Screening or Day -1 that require medical treatment or based on the investigator's opinion could affect the safety of the participant.
* Presence of orthostatic hypotension (≥30 millimeter of mercury \[mmHg\] drop in systolic blood pressure, or ≥20 mmHg drop in diastolic blood pressure) at Screening.
* Any history of gastrointestinal surgery that may affect pharmacokinetic of the study drug (e.g., hepatectomy, digestive organ resection).
* Positive urine drug test at Screening or Day -1; participants positive for tetrahydrocannabinol may be rescheduled at the discretion of the investigator.
* Positive breath alcohol test; participants with positive breath alcohol test may be rescheduled at the discretion of the investigator.
* Weight loss or gain of greater than 10% between Screening and dosing in each Treatment Period. Participants who are currently on, or plan to be on, a restrictive diet will be excluded at the discretion of the investigator.
* Known to be human immunodeficiency virus positive.
* Active viral hepatitis (B or C), as determined by positive serology at Screening.
* Donation or loss of more than 500 mL of whole blood within 30 days preceding the first dose of study drug.
* Treatment with an investigational drug within 28 days or 5-half-lives, whichever is longer, preceding the first dose of study drug. If the half-life is unknown, a 28-day period will apply.
* Use of prescription drugs within 2 weeks prior to dosing.
* Intake of over-the-counter medications within 2 weeks prior to dosing.
* Difficulty with venous access or unsuitable or unwilling to undergo catheter insertion.
* An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family member defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
* Has current pending legal charges or is currently on probation.
* Unwilling to be searched (including personal effects) for illicit substances before admission to or during the inpatient stays at the research clinic.
* In the opinion of the investigator, is considered unsuitable or unlikely to comply with the study protocol for any reason, including compliance with the study prohibitions and restrictions and completion of the cognitive performance and postural stability tasks.
* Previously participated in any clinical trial of lemborexant.

Primary outcomes:
measure: Change from baseline in body sway, as assessed by an ataxia meter measuring directional trunk movements, for lemborexant plus alcohol compared to lemborexant alone
timeFrame: Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period
measure: Change from baseline in body sway, as assessed by an ataxia meter measuring directional trunk movements, for lemborexant plus alcohol compared to alcohol alone
timeFrame: Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period
measure: Change from baseline in Power of Attention, per the Performance Assessment Battery (PAB), for lemborexant plus alcohol compared to lemborexant alone
timeFrame: Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period
measure: Change from baseline in Power of Attention, per the PAB, for lemborexant plus alcohol compared to alcohol alone
timeFrame: Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period
Secondary outcomes:
measure: Mean value of maximum observed concentration (Cmax) for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period
measure: Mean value of time at which the maximum drug concentration is observed (tmax) for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period
measure: Mean value of area under the concentration-time curve from zero time to time of last quantifiable concentration (AUC0-t) for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period
measure: Mean value of area under the concentration-time curve from zero time to 9 hours after dosing (AUC0-9h) for lemborexant
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6 and 9 hours postdose in each single-dose treatment period
measure: Mean value of area under the concentration-time curve from zero time to 12 hours after dosing (AUC0-12h) for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9 and 12 hours postdose in each single-dose treatment period
measure: Mean value of area under the concentration-time curve from zero time to 24 hours after dosing (AUC0-24h) for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours postdose in each single-dose treatment period
measure: Mean value of area under the concentration-time curve from zero time to 48 hours after dosing (AUC0-48h) for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 hours postdose in each single-dose treatment period
measure: Mean value of area under the concentration-time curve from zero time to 72 hours after dosing (AUC0-72h) for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period
measure: Mean value of terminal elimination phase half-life (t1/2) for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period
measure: Mean value of apparent total body clearance (CL/F) for lemborexant after extravascular administration
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period
measure: Mean value of AUC0-9h after dosing, metabolite ratio for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6 and 9 hours postdose in each single-dose treatment period
measure: Mean value of AUC0-12h after dosing, metabolite ratio for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9 and 12 hours postdose in each single-dose treatment period
measure: Mean value of AUC0-24h after dosing, metabolite ratio for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5,1.5, 2, 3, 4, 6, 9,12 and 24 hours postdose in each single-dose treatment period
measure: Mean AUC0-48h after dosing, metabolite ratio for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 hours postdose in each single-dose treatment period
measure: Mean value AUC0-72h after dosing, metabolite ratio for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period
measure: Mean value of time interval from dosing to the first measureable concentration (tlag) for lemborexant and its metabolites (M4, M9, and M10)
timeFrame: Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period
measure: Change from baseline in Continuity of Attention, per the PAB, for lemborexant plus alcohol compared to lemborexant alone, lemborexant plus alcohol compared to alcohol alone, and alcohol compared to placebo
timeFrame: Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period
measure: Change from baseline in Quality of Memory, per the PAB, for lemborexant plus alcohol compared to lemborexant alone, lemborexant plus alcohol compared to alcohol alone, and alcohol compared to placebo
timeFrame: Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period
measure: Change from baseline in Speed of Memory Retrieval, per the PAB, for lemborexant plus alcohol compared to lemborexant alone, lemborexant plus alcohol compared to alcohol alone, and alcohol compared to placebo
timeFrame: Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period
measure: Change from baseline in body sway, as assessed by an ataxia meter measuring directional trunk movements, for alcohol compared to placebo
timeFrame: Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period
measure: Change from baseline in Power of Attention, per the PAB, for alcohol compared to placebo
timeFrame: Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Syneos Health
state: Ontario
Study officials:
References: