Clinical trial NCT03012334: The Effects of Lasmiditan on Simulated Driving Performance - Healthy Participants
Official title: A Phase I, Randomized, Double-Blind, Placebo-Controlled, 5-Period, Cross-Over Study Assessing the Effects of Lasmiditan on Simulated Driving Performance in Normal Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Migraine
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Algorithme Pharma Inc
name: Cognitive Research Corporation
name: CoLucid Pharmaceuticals
First posted: 2017-01-06
Enrollment: 90
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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.

Primary outcomes:
measure: Simulated Driving Performance in Healthy Participants as Measured by Standard Deviation of Lateral Position (SDLP) Using the Cognitive Research Corporation Driving Simulator-MiniSim (CRCDS-MiniSim)
timeFrame: Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence
Secondary outcomes:
measure: Karolinska Sleepiness Scale (KSS) Score
timeFrame: Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence
measure: Percentage of Participants With Self-Reported Readiness to Drive
timeFrame: Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence
measure: Motivational and Self-Appraisal Visual Analog Scale (VAS)
timeFrame: Approximately 2.5 hours post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence
measure: Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test
timeFrame: Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence
measure: Driving Performance Using the CRCDS-MiniSim - Lane Exceedance
timeFrame: Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence
measure: Driving Performance Using the CRCDS-MiniSim - Speed Deviation
timeFrame: Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence
Other outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up To 35 days
Locations:
city: Mount Royal
country: Canada
facility: Algorithme Pharma
state: Quebec
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: