A Study of the Abuse Potential of Lasmiditan in Participants Who Are Recreational Drug Users

A Randomized, Subject- and Investigator-Blind, Placebo and Active-Controlled Study to Assess the Abuse Potential of Lasmiditan

The purpose of this study is to assess the abuse potential of study drug lasmiditan.

Lasmiditan will be compared to a marketed benzodiazepine, alprazolam (positive control), as well as to placebo (dummy substance that looks like lasmiditan or alprazolam without any active drug) to determine the potential for drug abuse. The dosages will be in tablet form and will be taken orally (by mouth).

This study will last about 55 days, including screening. Screening will occur within 28 days prior to qualification phase.

Study Overview

• Status: Completed
• Conditions: Prescription Drug Abuse (Not Dependent); Recreational Drug Use
• Intervention / Treatment: Drug: Placebo; Drug: Lasmiditan; Drug: Alprazolam

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince & Associates Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Are overtly healthy males or females, as determined by medical history and physical examination.
• Have a body mass index (BMI) of 18 to 32 kilograms per meter squared (kg/m²) inclusive, at the time of screening.
• Must be recreational drug user and agree not to consume any recreational drugs during the study.

Exclusion Criteria:

• Have known allergies to lasmiditan, alprazolam, related compounds, or any components of the formulation, or a history of significant atopy.
• Are currently seeking or participating in treatment for addiction or substance-related disorders, or have recovered from substance abuse disorder.
• Are currently taking excluded prescription or over-the-counter (OTC) medications.
• Have a history of significant sleep disorder, including sleep apnea or narcolepsy.
• Have a history of orthostatic hypotension, vertigo, syncope, or presyncope.
• Have a history of brain injury, including a history of concussions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo was administered orally in one of five treatment periods	Drug: Placebo; Administered orally
ACTIVE_COMPARATOR: Alprazolam 2 milligram (mg); 2 mg of alprazolam was administered orally in one of five treatment periods	Drug: Alprazolam; Administered orally
EXPERIMENTAL: Lasmiditan 100 mg; 100 mg of lasmiditan was administered orally in one of five treatment periods	Drug: Lasmiditan; Administered orally; Other Names: LY573144
EXPERIMENTAL: Lasmiditan 200 mg; 200 mg of lasmiditan was administered orally in one of five treatment periods	Drug: Lasmiditan; Administered orally; Other Names: LY573144
EXPERIMENTAL: Lasmiditan 400 mg; 400 mg of lasmiditan was administered orally in one of five treatment periods	Drug: Lasmiditan; Administered orally; Other Names: LY573144

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics (PD): Maximal Effect Score (Emax) of Bipolar Drug Liking Visual Analog Scale (VAS) Scores	The Emax of Bipolar Drug Liking VAS Scores were derived as the maximum at-the-moment Drug Liking VAS score where the time to Emax was the corresponding time point at which the maximum score occurred. The bipolar Drug Liking VAS is consistent with FDA Guidance (January 2017) such that placebo should produce a score between 40 and 60 representing neutral drug-liking (ie, neither like nor dislike); a score ranging from 0 to 100 and a score of 0 indicates strong disliking, and a score of 100 indicates strong liking. Least squares mean (LS mean) was calculated using a linear mixed-effects model, including period, sequence, and treatment as fixed effects, and subject as a random effect, was used to evaluate the hypothesis tests of primary interest (at-the-moment Drug Liking) at the Emax.	Each Phase: 24 Hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan	Pharmacokinetics (PK) defined as the maximum observed drug concentration (Cmax) of lasmiditan	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours Post Dose
PK: Area Under the Curve of Lasmiditan From Zero to Infinity (AUC[0-∞])	PK defined as the area under the curve of lasmiditan from zero to infinity (AUC[0-∞])	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours Post Dose
PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS)	Drug Effects VAS Battery lists a series of measures that evaluate different effects of the abuse potential of the study drug. Scales include: Overall drug liking (overall, my liking for this drug is) and ranges from 0 definitely not to 100 definitely so. Take Drug Again (I would take this drug again) and ranges from 0 definitely not to 100 definitely so. Good effects (I can feel good drug effects) and ranges from 0 definitely not to 100 definitely so. Bad effects (I can feel bad drug effects) and ranges from 0 definitely not to 100 definitely so. High (I am feeling) and ranges from 0 not at all high to 100 extremely high. Emax is derived as the maximum score across all postdose time points for each participant. Least Square (LS) Mean is calculated using the linear mixed-effects model with period, sequence and treatment as fixed effects and participant as a random effect.	Each Phase: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 4.5, 5, 6, 8, 12, 24 Hours Post Dose
PD: Maximal Drug Effects (Emax) VAS (Hallucinations)	Drug Effects VAS Battery lists a series of measures that evaluate different effects of the abuse potential of the study drug. The hallucinations scale is presented meaning (I am hallucinating) and ranges from 0 not at all to 100 extremely. Emax is derived as the maximum score across all postdose time points for each participant. Median and interquartile range are reported for each treatment group.	Each Phase: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 4.5, 5, 6, 8, 12, 24 Hours Post Dose
PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS)	Drug Effects VAS Battery lists a series of measures that evaluate different effects of the abuse potential of the study drug. The scales included: Alertness/Drowsiness (I am feeling) ranges from 0 very drowsy to 100 very alert. Agitation/Relaxation (my mood is) and ranges from 0 very relaxed to 100 very agitated. Emin is derived across all postdose time points for each participant. LS Mean was calculated using the linear mixed-effects model with period, sequence and treatment as fixed effects and participant as a random effect.	Each Phase:Predose, 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 4.5, 5, 6, 8, 12, 24 Hours Post Dose
PD: Mean Scores on Drug Similarity VAS Measures	Participants marked a point on a 100-mm horizontal line that best represented their response to the given question. The endpoints of each electronic scale were marked with descriptive anchors on a scale from 0 to 100 (Fraser et al. 1961; Bond and Lader 1974; Bigelow 1991; Shram et al. 2010). In the "How similar" questions, ranges from 0 to 100 and a score of 0 indicates definitely not similar, and a score of 100 indicates definitely similar.	Each Phase: 24 Hours Post Dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 15, 2017
• Primary Completion (ACTUAL): November 20, 2017
• Study Completion (ACTUAL): November 20, 2017

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: September 15, 2017
• First Posted (ACTUAL): September 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 10, 2020
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Alprazolam; Lasmiditan
• Other Study ID Numbers: 16853; H8H-MC-LAHB (OTHER: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No