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

Phase 1

Completed

Conditions: Recreational Drug Use
Prescription Drug Abuse (Not Dependent)

Interventions: Drug: Placebo
Drug: Lasmiditan
Drug: Alprazolam

Registration Number: NCT03286218

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 96

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo was administered orally in one of five treatment periods
Lasmiditan 400 mg	Lasmiditan	400 mg of lasmiditan was administered orally in one of five treatment periods
Alprazolam 2 milligram (mg)	Alprazolam	2 mg of alprazolam was administered orally in one of five treatment periods
Lasmiditan 100 mg	Lasmiditan	100 mg of lasmiditan was administered orally in one of five treatment periods
Lasmiditan 200 mg	Lasmiditan	200 mg of lasmiditan was administered orally in one of five treatment periods

Primary Outcome Measures

Name	Time	Method
Pharmacodynamics (PD): Maximal Effect Score (Emax) of Bipolar Drug Liking Visual Analog Scale (VAS) Scores	Each Phase: 24 Hours	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.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): 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	Pharmacokinetics (PK) defined as the maximum observed drug concentration (Cmax) of lasmiditan
PK: 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	PK defined as the area under the curve of lasmiditan from zero to infinity (AUC\[0-∞\])
PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS)	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	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.
PD: Maximal Drug Effects (Emax) VAS (Hallucinations)	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	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.
PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS)	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	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.
PD: Mean Scores on Drug Similarity VAS Measures	Each Phase: 24 Hours Post Dose	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.