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

• Lasmiditan (Drug), also known as LY573144: Administered orally
• Alprazolam (Drug): Administered orally
• Placebo (Drug): Administered orally

Primary outcomes

• 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 outcomes

• 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.

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• Pharmacodynamics (PD): Maximal Effect Score (Emax) of Bipolar Drug Liking Visual Analog Scale (VAS) Scores (Primary), Least squares mean, millimeter (mm): Placebo 53.0 +/- 1.94; Alprazolam - 2 mg 85.4 +/- 1.94; Lasmiditan - 100 mg 68.6 +/- 1.94; Lasmiditan - 200 mg 73.3 +/- 1.94; Lasmiditan - 400 mg 76.6 +/- 1.94
• Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan (Secondary), Geometric mean, nanogram/milliliter (ng/mL): Lasmiditan - 100 mg 132 +/- 37; Lasmiditan - 200 mg 299 +/- 35; Lasmiditan - 400 mg 689 +/- 34
• PK: Area Under the Curve of Lasmiditan From Zero to Infinity (AUC[0-∞]) (Secondary), Geometric mean, nanogram*hour/milliliter (ng*h/mL): Lasmiditan - 100 mg 856 +/- 32; Lasmiditan - 200 mg 1810 +/- 35; Lasmiditan - 400 mg Dose 3920 +/- 28
• PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) (Secondary), Least squares mean, mm: Placebo 53.1 +/- 2.41; Alprazolam - 2 mg 86.2 +/- 2.41; Lasmiditan - 100 mg 71.7 +/- 2.41; Lasmiditan - 200 mg 72.2 +/- 2.41; Lasmiditan - 400 mg 77.4 +/- 2.41
• PD: Maximal Drug Effects (Emax) VAS (Hallucinations) (Secondary), Median, mm: Placebo 0 (0 to 0); Alprazolam - 2 mg 0 (0 to 1.00); Lasmiditan - 100 mg 0 (0 to 0); Lasmiditan - 200 mg 0 (0 to 0); Lasmiditan - 400 mg 0 (0 to 0) (p <0.0001)
• PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) (Secondary), Least squares mean, mm: Placebo 42.5 +/- 1.97; Alprazolam - 2 mg 12.5 +/- 1.97; Lasmiditan - 100 mg 25.6 +/- 1.97; Lasmiditan - 200 mg 22.9 +/- 1.97; Lasmiditan - 400 mg 17.7 +/- 1.97
• PD: Mean Scores on Drug Similarity VAS Measures (Secondary), Mean, score on a scale: Placebo - Qualification Phase 1.3 +/- 3.5; 1 mg Alprazolam - Qualification Phase 5.8 +/- 10.6; Placebo 2.2 +/- 6.6; 2 mg Alprazolam 6.1 +/- 13.6; Lasmiditan - 100 mg 2.7 +/- 4.2; Lasmiditan - 200 mg 14.6 +/- 26.3; Lasmiditan - 400 mg 12.5 +/- 23.3

Adverse events

Time frame: From Baseline to Study Completion (Up to 2 months)

Other adverse events by term

• Study Protocol (PDF, 2017-09-05)
• Statistical Analysis Plan (PDF, 2017-09-11)

• 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), Study director, Eli Lilly and Company