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

Eli Lilly and Company96 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Recreational Drug Use Prescription Drug Abuse (Not Dependent)

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Each Phase: 24 Hours

Secondary Outcomes

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan

Pharmacokinetics (PK) defined as the maximum observed drug concentration (Cmax) of lasmiditan

Time frame: 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\[0-∞\])

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Each Phase: 24 Hours Post Dose