Study of Lemborexant-Alcohol Interaction in Healthy Subjects

NCT03483636 | Completed Phase 1 FDA Drug

• 1 other identifier: E2006-A001-009
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Keywords

Drug-alcohol interaction; Lemborexant; E2006; Postural stability; Cognitive performance

Outcome Measures

Primary Outcomes (4)

• Change from baseline in body sway, as assessed by an ataxia meter measuring directional trunk movements, for lemborexant plus alcohol compared to lemborexant alone

  Body sway will be detected through a cable around the participant's waist by the ataxia meter. Body sway will be measured in units of 1/3° of the angle of arc. For ease in reporting, these will be called arbitrary units, with a higher number indicating more body sway (less postural stability).

  Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period

• Change from baseline in body sway, as assessed by an ataxia meter measuring directional trunk movements, for lemborexant plus alcohol compared to alcohol alone

  Body sway will be detected through a cable around the participant's waist by the ataxia meter. Body sway will be measured in units of 1/3° of the angle of arc. For ease in reporting, these will be called arbitrary units, with a higher number indicating more body sway (less postural stability).

  Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period

• Change from baseline in Power of Attention, per the Performance Assessment Battery (PAB), for lemborexant plus alcohol compared to lemborexant alone

  The PAB comprises 9 tasks: Simple Reaction Time; Choice Reaction Time; Digit Vigilance; Immediate Word Recall; Delayed Word Recall; Numerical Working Memory; Spatial Working Memory; Word Recognition; Picture Recognition. Four composite domain factor scores will be calculated by combining outcome variables from the various tests. The 4 domains are Power of Attention, Continuity of Attention, Quality of Memory, and Speed of Memory Retrieval. The Power of Attention score is a composite score from the speed scores of 3 tests of attention (Simple Reaction Time, Choice Reaction Time, Digit Vigilance) and reflects the ability to focus attention and process information. A higher score indicates better performance.

  Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period

• Change from baseline in Power of Attention, per the PAB, for lemborexant plus alcohol compared to alcohol alone

  The PAB comprises 9 tasks: Simple Reaction Time; Choice Reaction Time; Digit Vigilance; Immediate Word Recall; Delayed Word Recall; Numerical Working Memory; Spatial Working Memory; Word Recognition; Picture Recognition. Four composite domain factor scores will be calculated by combining outcome variables from the various tests. The 4 domains are Power of Attention, Continuity of Attention, Quality of Memory, and Speed of Memory Retrieval. The Power of Attention score is a composite score from the speed scores of 3 tests of attention (Simple Reaction Time, Choice Reaction Time, Digit Vigilance) and reflects the ability to focus attention and process information. A higher score indicates better performance.

  Baseline; Up to approximately 12 weeks postdose in each single-dose treatment period

Secondary Outcomes (21)

• Mean value of maximum observed concentration (Cmax) for lemborexant and its metabolites (M4, M9, and M10)

  Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period

• Mean value of time at which the maximum drug concentration is observed (tmax) for lemborexant and its metabolites (M4, M9, and M10)

  Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period

• 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)

  Predose; 0.5, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, 48, and 72 hours postdose in each single-dose treatment period

• Mean value of area under the concentration-time curve from zero time to 9 hours after dosing (AUC0-9h) for lemborexant

  Predose; 0.5, 1.5, 2, 3, 4, 6 and 9 hours postdose in each single-dose treatment period

• 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)

  Predose; 0.5, 1.5, 2, 3, 4, 6, 9 and 12 hours postdose in each single-dose treatment period

Study Arms (4)

Lemborexant

EXPERIMENTAL

Participants will be randomized to receive a 10 milligram (mg) lemborexant tablet administered with 50 milliliter (mL) water followed by a total volume of 300 mL (approximately 150 mL per aliquot) of a low-calorie beverage (e.g., cranberry beverage) after an overnight fast of at least 8 hours and a sleep period of at least 8 hours. Treatment will be administered after a light breakfast (ie, not high fat), at approximately 120 minutes after wake time in the morning.

Drug: Lemborexant

Lemborexant Plus Alcohol

EXPERIMENTAL

Participants will be randomized to receive a 10 mg lemborexant tablet administered with 50 mL water followed by alcohol (0.6 grams per kilogram \[g/kg\] of alcohol for females or 0.7 g/kg of alcohol for males) for a total volume of 300 mL (approximately 150 mL per aliquot) of a low-calorie beverage (e.g., cranberry beverage) after an overnight fast of at least 8 hours and a sleep period of at least 8 hours. Treatment will be administered after a light breakfast (ie, not high fat), at approximately 120 minutes after wake time in the morning.

Drug: Lemborexant; Drug: Alcohol

Alcohol

EXPERIMENTAL

Participants will be randomized to receive a 10 mg lemborexant-matched placebo tablet administered with 50 mL water followed by alcohol (0.6 g/kg of alcohol for females or 0.7 g/kg of alcohol for males) for a total volume of 300 mL (approximately 150 mL per aliquot) of a low-calorie beverage (e.g., cranberry beverage) after an overnight fast of at least 8 hours and a sleep period of at least 8 hours. Treatment will be administered after a light breakfast (ie, not high fat), at approximately 120 minutes after wake time in the morning.

Drug: Alcohol; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Participants will be randomized to receive a 10 mg lemborexant-matched placebo tablet administered with 50 mL water followed by alcohol for a total volume of 300 mL (approximately 150 mL per aliquot) of a low-calorie beverage (e.g., cranberry beverage) after an overnight fast of at least 8 hours and a sleep period of at least 8 hours. Treatment will be administered after a light breakfast (ie, not high fat), at approximately 120 minutes after wake time in the morning.

Drug: Placebo

Interventions

Lemborexant DRUG

Film-coated oral tablet

Lemborexant; Lemborexant Plus Alcohol

Alcohol DRUG

0.6 g/kg (female) or 0.7 g/kg (male) of 40% ethanol (volume per volume) vodka diluted in a low-calorie beverage (e.g., cranberry beverage), for a total volume of 300 mL (approximately 150 mL per aliquot).

Also known as: E2006

Alcohol; Lemborexant Plus Alcohol

Placebo DRUG

Film-coated oral tablet

Alcohol; Placebo

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• ≥15 on Apnea subscales
• ≥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).

Sponsors & Collaborators

• Eisai Inc.: lead
• Purdue Pharma LP: collaborator

Study Sites (1)

Syneos Health

Toronto, Ontario, M5V 2T3, Canada

Location

MeSH Terms

Interventions

lemborexant; Ethanol

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 30, 2018
• Study Start: March 12, 2018
• Primary Completion: September 12, 2018
• Study Completion: September 12, 2018
• Last Updated: October 17, 2018

Record last verified: 2018-07

Locations

CA (1)