The Effects of Lasmiditan on Simulated Driving Performance - Healthy Participants

NCT03012334 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 16883COL MIG-106H8H-CD-LAHG
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine

Outcome Measures

Primary Outcomes (1)

• 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)

  The standard deviation of lateral position (SDLP) is the primary parameter used as stable measure of driving performance with high test-retest reliability. It measures the driver's ability to stay in a constant position within the driving lane. Variations in the lateral position are recorded and analyzed. SDLP, was analyzed using a mixed model with fixed effects for sequence, period, and treatment, and a random effect for participant within sequence. A variance component covariance structure and Kenward-Roger degrees of freedom was used.

  Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence

Secondary Outcomes (6)

• Karolinska Sleepiness Scale (KSS) Score

  Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence

• Percentage of Participants With Self-Reported Readiness to Drive

  Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence

• Motivational and Self-Appraisal Visual Analog Scale (VAS)

  Approximately 2.5 hours post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence

• Number of Correct Responses in Driving Performance Using CogScreen Symbol Digit Coding (SDC) Test

  Approximately 85 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence

• Driving Performance Using the CRCDS-MiniSim - Lane Exceedance

  Approximately 90 minutes post dose, on Day 1, 7, 14, 21, or 28 depending upon the assigned treatment sequence

Other Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up To 35 days

Study Arms (5)

Lasmiditan 50mg (milligrams)

EXPERIMENTAL

Participants received 50mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning.

Drug: Lasmiditan

Lasmiditan 100mg

EXPERIMENTAL

Participants received 100mg of Lasmiditan tablets given as single oral doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning.

Drug: Lasmiditan

Lasmiditan 200mg

EXPERIMENTAL

Participants received 200mg of Lasmiditan tablets given as single doses on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning.

Drug: Lasmiditan

Alprazolam 1mg

ACTIVE COMPARATOR

Participants received 1mg of Alprazolam tablets as single oral dose on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning.

Drug: Alprazolam

Placebo

PLACEBO COMPARATOR

Participants received placebo tablets identical to Lasmiditan, administered as single oral dose on Day 1, 7, 14, 21, or 28 (dependent upon the assigned treatment sequence) in the morning.

Other: Placebo

Interventions

Lasmiditan DRUG

Dose is based on treatment sequence in 5-way crossover

Also known as: LY573144

Lasmiditan 100mg; Lasmiditan 200mg; Lasmiditan 50mg (milligrams)

Alprazolam DRUG

Active comparator based on treatment sequence in 5-way crossover

Alprazolam 1mg

Placebo OTHER

Placebo comparator based on treatment sequence in 5-way crossover

Placebo

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Algorithme Pharma Inc: collaborator
• Cognitive Research Corporation: collaborator
• CoLucid Pharmaceuticals: collaborator

Study Sites (1)

Algorithme Pharma

Mount Royal, Quebec, H3P3P1, Canada

Location

MeSH Terms

Conditions

Migraine Disorders

Interventions

lasmiditan; Alprazolam

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2016
• First Posted: January 6, 2017
• Study Start: January 16, 2017
• Primary Completion: June 8, 2017
• Study Completion: June 8, 2017
• Last Updated: January 10, 2020
• Results First Posted: January 10, 2020

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)