The Effects of Lasmiditan on Simulated Driving Performance - Healthy Participants
Condition: Migraine
Intervention: Lasmiditan; Alprazolam; Placebo
Intervention description: Dose is based on treatment sequence in 5-way crossover; Active comparator based on treatment sequence in 5-way crossover; Placebo comparator based on treatment sequence in 5-way crossover
Intervention MeSH terms: Alprazolam; Lasmiditan
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 90.0
Sex: All
Minimum age: 21 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This will be a randomized, single dose, double-blind, placebo-controlled, Latin-square design
      with 5-period (full) crossover study with participants randomized to treatment sequences.
      Participants will complete all 5 Periods.

      During each Period, participants will come to the clinical research unit (CRU) and remain
      overnight before being dosed with a single dose of either lasmiditan, alprazolam, or placebo
      in the morning. Cognitive testing and driving simulation will be conducted post dosing.
      Participants will have a washout of at least 5 days between each Period.

      This study is designed to test non-inferiority of lasmiditan doses relative to placebo, with
      an alprazolam test versus placebo to confirm the sensitivity of the simulator to detect
      treatment effects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able and willing to voluntarily consent to participate in this study and provide
             written informed consent prior to start of any study-specific procedures.

          -  Males and females between the ages of 21 and 50 years of age (inclusive). No more than
             60% of one gender will be enrolled in the study.

          -  Body Mass Index (BMI) between 18 and 32 kilograms per meter squared (kg/m²)
             (inclusive).

          -  Participant is able to reliably perform study assessments (Standard Deviation of
             Lateral Position (SDLP) no higher than 1 standard deviation greater than the mean for
             normal healthy adults completing the practice scenario; Symbol Digit Coding (SDC)
             Correct no less than 1 standard deviation below the mean for healthy adults in their
             age range); demonstrates the ability to understand task instructions, and is
             physically capable (e.g., adequate manual dexterity, vision, and hearing) and
             cognitively capable of performing study tasks.

          -  Participant possesses a valid driver's license and is an active driver. Drives a
             minimum of 10,000 miles (about 16,000 km) per year for the previous 3 years.

          -  Participant must also demonstrate simulator sickness questionnaire scores which are
             not indicative of simulator sickness as defined in the driving simulation operations
             manual.

          -  Participant has a regular sleep pattern, is not engaged in shift-work, and in general,
             has at least 7 hours of sleep each night (bedtime occurs between 21:00 and 24:00
             hours).

          -  Participant has a score < 10 on the Epworth Sleepiness Scale.

          -  Use of a medically highly effective form of birth control during the study and for
             thirty (30) days:

          -  Participants who are willing and able to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures.

        Exclusion Criteria:

          -  History or presence of clinically significant condition that, in the opinion of the
             Investigator, would jeopardize the safety of the participant or the validity of the
             study results.

          -  A history within 2 years of, or current treatment for, a sleeping disorder (including
             excessive snoring, obstructive sleep apnea), or a chronic painful condition that
             interferes with the participant's sleep.

          -  A history of difficulty either falling asleep or staying asleep in the previous 3
             months, that is considered clinically significant by the investigator.

          -  Participant has a history or diagnosis of any of the following conditions:

               -  Primary or secondary insomnia

               -  Narcolepsy

               -  Cataplexy (familial or idiopathic)

               -  Circadian Rhythm Sleep Disorder

               -  Parasomnia including nightmare disorder, sleep terror disorder, sleepwalking
                  disorder, and rapid eye movement behavior disorder

               -  Sleep-related Breathing Disorder (obstructive or central sleep apnea syndrome,
                  central alveolar hypoventilation syndrome)

               -  Periodic Limb Movement Disorder

               -  Restless Legs Syndrome

               -  Primary Hypersomnia

               -  Excessive Daytime Sleepiness (EDS)

               -  Participant has visual or auditory impairment which in the opinion of the
                  investigator would interfere with study related procedures or study conduct.

          -  Expected to use any other medication or dietary supplement to promote sleep including
             over- the-counter sleep medications, during their participation in the study.

          -  Participant consumes excessive amounts of coffee, tea, cola, or other caffeinated
             beverages per day.

          -  Participant has traveled across 1 or more time zones (transmeridian travel) in the
             last 2 weeks prior to randomization or is expected to travel across 1 or more time
             zones during the study.

          -  Expected to work on a rotating shift during their participation in the study.

          -  Participant works a night shift.

          -  History or presence of seizure disorder.

          -  History of urinary retention, angle closure glaucoma, or increased ocular pressure.

          -  History of gastrointestinal tract surgery, except for appendectomy.

          -  Has abnormal finding on the physical exam, medical history, electrocardiogram (ECG),
             or clinical laboratory results at Screening, that are considered clinically
             significant by the investigator.

          -  Presence of out-of-range cardiac interval on the screening ECG or other clinically
             significant ECG abnormalities

          -  History of orthostatic hypotension, fainting spells, or blackouts, that are considered
             clinically significant by the investigator.

          -  The presence of chronic or acute infections, that are considered clinically
             significant by the investigator.

          -  History of allergy/hypersensitivity (including drug allergies) that are deemed
             relevant to the study as judged by the Investigator.

          -  Use of psychoactive prescription or non-prescription medications, psychoactive
             nutritional supplements or herbal preparations within 2 weeks or 5 half-lives
             (whichever is longer) of admission to the clinical research unit (CRU) on Day -1.

          -  Has received any previous study drug within 30 days prior to the first dose of this
             study drug.

          -  Is a smoker of more than 10 cigarettes or eCigarettes, or 3 cigars or 3 pipes per day,
             and is unable to refrain from smoking while confined to the CRU.

          -  Has any history of dependency or treatment for substance abuse within the past 2
             years.

          -  Participant with a history of alcoholism or who consumes excessive amounts of alcohol.

          -  Participants who consume alcohol on a regular basis (i.e., ≥ 5 times/week) before
             bedtime will be excluded from the study.

          -  Inability to comply with the dietary regimen of the clinical research center.

          -  Pregnancy / positive pregnancy test.

          -  Planning to become pregnant during the study or within 1 month of study completion.

          -  Inability to use adequate contraception during the study. It is recommended that
             adequate contraception be used for 30 days following completion of the study.

          -  Has a positive screen for alcohol or other drugs of abuse (amphetamines,
             methamphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates).

          -  Has a history for Hepatitis B, Hepatitis C , or Human Immunodeficiency Virus (HIV) at
             Screening or has been previously treated for Hepatitis B, Hepatitis C, or HIV.