Prescription Drug Abuse (Not Dependent), Recreational Drug Use
Conditions
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.
Interventions
DRUGLasmiditan
Administered orally
DRUGAlprazolam
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
Qualification Phase: Participants randomized in a 2-period crossover design with a washout period of at least 72 hours Treatment Phase: Participants randomized to 1 of 10 dosing sequences, irrespective of their qualification randomization, in a 5-period crossover design with a washout period of 3 days in between doses.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants All participants received one dose of alprazolam and placebo in the qualification phase and participants received at least one dose lasmiditan, alprazolam and/or placebo in the treatment phase. | 96 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Qualification Phase Period 1 | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Qualification Phase Period 1 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Qualification Phase Period 2 | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Qualification Phase Period 2 | Failure to meet randomization criteria | 14 | 15 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Qualification Phase Period 2 | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Qualification Phase Period 2 | Protocol Violation | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Qualification Phase Period 2 | Withdrawal by Subject | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Phase Period 1 | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Phase Period 4 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Overall Participants |
|---|---|
| Age, Continuous | 31.4 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 69 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment United States | 96 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 95 | 0 / 94 | 0 / 55 | 0 / 53 | 0 / 55 | 0 / 55 | 0 / 55 |
| other Total, other adverse events | 8 / 95 | 74 / 94 | 12 / 55 | 49 / 53 | 33 / 55 | 42 / 55 | 47 / 55 |
| serious Total, serious adverse events | 0 / 95 | 0 / 94 | 0 / 55 | 0 / 53 | 0 / 55 | 0 / 55 | 0 / 55 |
Outcome results
Primary
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
Population: All randomized participants who received at least one dose of study drug had evaluable PD data in each of the 5 periods.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximal Effect Score (Emax) of Bipolar Drug Liking Visual Analog Scale (VAS) Scores | 53.0 millimeter (mm) | Standard Error 1.94 |
| Alprazolam - 2 mg | Pharmacodynamics (PD): Maximal Effect Score (Emax) of Bipolar Drug Liking Visual Analog Scale (VAS) Scores | 85.4 millimeter (mm) | Standard Error 1.94 |
| Lasmiditan - 100 mg | Pharmacodynamics (PD): Maximal Effect Score (Emax) of Bipolar Drug Liking Visual Analog Scale (VAS) Scores | 68.6 millimeter (mm) | Standard Error 1.94 |
| Lasmiditan - 200 mg | Pharmacodynamics (PD): Maximal Effect Score (Emax) of Bipolar Drug Liking Visual Analog Scale (VAS) Scores | 73.3 millimeter (mm) | Standard Error 1.94 |
| Lasmiditan - 400 mg | Pharmacodynamics (PD): Maximal Effect Score (Emax) of Bipolar Drug Liking Visual Analog Scale (VAS) Scores | 76.6 millimeter (mm) | Standard Error 1.94 |
90% CI: [28.4, 36.4]
90% CI: [11.7, 19.6]
90% CI: [16.3, 24.3]
90% CI: [19.6, 27.6]
90% CI: [12.8, 20.8]
90% CI: [8.1, 16.1]
90% CI: [4.8, 12.8]
Secondary
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
Population: All randomized participants who received at least one dose of study drug and had evaluable PD data, and completed the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | PD: Maximal Drug Effects (Emax) VAS (Hallucinations) | 0 mm |
| Alprazolam - 2 mg | PD: Maximal Drug Effects (Emax) VAS (Hallucinations) | 0 mm |
| Lasmiditan - 100 mg | PD: Maximal Drug Effects (Emax) VAS (Hallucinations) | 0 mm |
| Lasmiditan - 200 mg | PD: Maximal Drug Effects (Emax) VAS (Hallucinations) | 0 mm |
| Lasmiditan - 400 mg | PD: Maximal Drug Effects (Emax) VAS (Hallucinations) | 0 mm |
p-value: <0.0001Wilcoxon (Mann-Whitney)
p-value: 0.0781Wilcoxon (Mann-Whitney)
p-value: 0.0625Wilcoxon (Mann-Whitney)
p-value: 0.0098Wilcoxon (Mann-Whitney)
Secondary
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
Population: All randomized participants who received at least one dose of study drug and had evaluable PD data, and completed the study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Overall Drug Liking | 53.1 mm | Standard Error 2.41 |
| Placebo | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Take Drug Again | 52.0 mm | Standard Error 2.7 |
| Placebo | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Good Effects | 10.8 mm | Standard Error 4.1 |
| Placebo | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Bad Effects | 2.47 mm | Standard Error 3.22 |
| Placebo | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Any Effects | 8.35 mm | Standard Error 4.05 |
| Placebo | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | High | 8.61 mm | Standard Error 3.89 |
| Alprazolam - 2 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Any Effects | 83.7 mm | Standard Error 4.05 |
| Alprazolam - 2 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | High | 77.2 mm | Standard Error 3.89 |
| Alprazolam - 2 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Overall Drug Liking | 86.2 mm | Standard Error 2.41 |
| Alprazolam - 2 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Good Effects | 80.5 mm | Standard Error 4.1 |
| Alprazolam - 2 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Bad Effects | 22.9 mm | Standard Error 3.22 |
| Alprazolam - 2 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Take Drug Again | 86.0 mm | Standard Error 2.7 |
| Lasmiditan - 100 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Bad Effects | 7.51 mm | Standard Error 3.22 |
| Lasmiditan - 100 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Any Effects | 53.3 mm | Standard Error 4.05 |
| Lasmiditan - 100 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Overall Drug Liking | 71.7 mm | Standard Error 2.41 |
| Lasmiditan - 100 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Good Effects | 46.4 mm | Standard Error 4.1 |
| Lasmiditan - 100 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Take Drug Again | 71.1 mm | Standard Error 2.7 |
| Lasmiditan - 100 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | High | 43.0 mm | Standard Error 3.89 |
| Lasmiditan - 200 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Bad Effects | 9.75 mm | Standard Error 3.22 |
| Lasmiditan - 200 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Take Drug Again | 72.7 mm | Standard Error 2.7 |
| Lasmiditan - 200 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Good Effects | 62.9 mm | Standard Error 4.1 |
| Lasmiditan - 200 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | High | 56.1 mm | Standard Error 3.89 |
| Lasmiditan - 200 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Any Effects | 65.1 mm | Standard Error 4.05 |
| Lasmiditan - 200 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Overall Drug Liking | 72.2 mm | Standard Error 2.41 |
| Lasmiditan - 400 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Any Effects | 73.2 mm | Standard Error 4.04 |
| Lasmiditan - 400 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Good Effects | 63.8 mm | Standard Error 4.1 |
| Lasmiditan - 400 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Take Drug Again | 77.3 mm | Standard Error 2.7 |
| Lasmiditan - 400 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | High | 67.0 mm | Standard Error 3.89 |
| Lasmiditan - 400 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Bad Effects | 15.0 mm | Standard Error 3.22 |
| Lasmiditan - 400 mg | PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS) | Overall Drug Liking | 77.4 mm | Standard Error 2.41 |
Comparison: Overall Drug Liking90% CI: [28.5, 37.7]
Comparison: Overall Drug Liking90% CI: [14, 23.2]
Comparison: Overall Drug Liking90% CI: [14.5, 23.8]
Comparison: Overall Drug Liking90% CI: [19.7, 28.9]
Comparison: Take drug again90% CI: [29.1, 38.9]
Comparison: Take drug again90% CI: [14.2, 24]
Comparison: Take drug again90% CI: [15.7, 25.6]
Comparison: Take drug again90% CI: [20.3, 30.2]
Comparison: Good effects90% CI: [62.1, 77.4]
Comparison: Good effects90% CI: [27.9, 43.2]
Comparison: Good effects90% CI: [44.4, 59.7]
Comparison: Good effects90% CI: [45.4, 60.6]
Comparison: Bad effects90% CI: [13.6, 27.2]
Comparison: Bad effects90% CI: [-1.76, 11.8]
Comparison: Bad effects90% CI: [0.487, 14.1]
Comparison: Bad effects90% CI: [5.69, 19.3]
Comparison: Any effects90% CI: [67.2, 83.5]
Comparison: Any effects90% CI: [36.8, 53]
Comparison: Any effects90% CI: [48.7, 64.9]
Comparison: Any effects90% CI: [56.7, 73]
Comparison: High90% CI: [60.6, 76.6]
Comparison: High90% CI: [26.4, 42.4]
Comparison: High90% CI: [39.5, 55.5]
Comparison: High90% CI: [50.4, 66.3]
Secondary
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
Population: All randomized participants who received at least one dose of study drug, were familiar with each listed drug on the questionnaire and had evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to codeine or morphine use | 11.4 score on a scale | Standard Deviation 23.8 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to heroin | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to nicotine | 2.9 score on a scale | Standard Deviation 11.8 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to (lysergic acid diethylamide (LSD) | 1.2 score on a scale | Standard Deviation 3.9 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar with caffeine | 2.9 score on a scale | Standard Deviation 10.3 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar with cocaine / | 1.3 score on a scale | Standard Deviation 3.5 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to MDMA (Ectasy) | 4.7 score on a scale | Standard Deviation 13.5 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to mushrooms | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to amphetamine or methamphetamine | 1.5 score on a scale | Standard Deviation 5.4 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to benzodiazepine | 14.4 score on a scale | Standard Deviation 32.4 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to phencyclidine (PCP) | 22.0 score on a scale | Standard Deviation 30.6 |
| Placebo | PD: Mean Scores on Drug Similarity VAS Measures | How similar to cannabis | 10.8 score on a scale | Standard Deviation 24.7 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with cocaine / | 5.8 score on a scale | Standard Deviation 10.6 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to heroin | 17.8 score on a scale | Standard Deviation 38.1 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to MDMA (Ectasy) | 10.0 score on a scale | Standard Deviation 20.4 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to benzodiazepine | 75.9 score on a scale | Standard Deviation 36.2 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to codeine or morphine use | 41.5 score on a scale | Standard Deviation 35.1 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to (lysergic acid diethylamide (LSD) | 4.1 score on a scale | Standard Deviation 6.9 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to cannabis | 39.9 score on a scale | Standard Deviation 33.5 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to nicotine | 5.1 score on a scale | Standard Deviation 9.6 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with caffeine | 3.2 score on a scale | Standard Deviation 6 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to amphetamine or methamphetamine | 4.3 score on a scale | Standard Deviation 6.3 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to mushrooms | 2.7 score on a scale | Standard Deviation 3.8 |
| Alprazolam - 2 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to phencyclidine (PCP) | 0.5 score on a scale | Standard Deviation 1 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to heroin | NA score on a scale | — |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to phencyclidine (PCP) | 0.0 score on a scale | Standard Deviation 0 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to MDMA (Ectasy) | 1.4 score on a scale | Standard Deviation 3.9 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to benzodiazepine | 13.1 score on a scale | Standard Deviation 30.6 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to amphetamine or methamphetamine | 2.4 score on a scale | Standard Deviation 6 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to mushrooms | 2.1 score on a scale | Standard Deviation 5.2 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to codeine or morphine use | 8.1 score on a scale | Standard Deviation 21.7 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to nicotine | 1.4 score on a scale | Standard Deviation 5.5 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to cannabis | 8.9 score on a scale | Standard Deviation 22.9 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to (lysergic acid diethylamide (LSD) | 4.2 score on a scale | Standard Deviation 6.6 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with caffeine | 1.5 score on a scale | Standard Deviation 7.2 |
| Lasmiditan - 100 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with cocaine / | 2.2 score on a scale | Standard Deviation 6.6 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to mushrooms | 3.7 score on a scale | Standard Deviation 6.1 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with cocaine / | 6.1 score on a scale | Standard Deviation 13.6 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with caffeine | 4.4 score on a scale | Standard Deviation 9.7 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to MDMA (Ectasy) | 20.5 score on a scale | Standard Deviation 23.7 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to amphetamine or methamphetamine | 3.9 score on a scale | Standard Deviation 5.5 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to phencyclidine (PCP) | 26.7 score on a scale | Standard Deviation 40.3 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to codeine or morphine use | 50.8 score on a scale | Standard Deviation 31.2 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to (lysergic acid diethylamide (LSD) | 6.2 score on a scale | Standard Deviation 7.5 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to nicotine | 3.8 score on a scale | Standard Deviation 9.4 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to cannabis | 51.2 score on a scale | Standard Deviation 30.3 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to benzodiazepine | 88.1 score on a scale | Standard Deviation 22.6 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to heroin | NA score on a scale | — |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to cannabis | 29.9 score on a scale | Standard Deviation 30 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with cocaine / | 2.7 score on a scale | Standard Deviation 4.2 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to MDMA (Ectasy) | 10.6 score on a scale | Standard Deviation 19.9 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to amphetamine or methamphetamine | 2.3 score on a scale | Standard Deviation 2.5 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to benzodiazepine | 57.2 score on a scale | Standard Deviation 40.3 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to nicotine | 3.3 score on a scale | Standard Deviation 11 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to (lysergic acid diethylamide (LSD) | 3.5 score on a scale | Standard Deviation 4.6 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to mushrooms | 2.1 score on a scale | Standard Deviation 2.1 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to phencyclidine (PCP) | 1.3 score on a scale | Standard Deviation 1.5 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with caffeine | 2.2 score on a scale | Standard Deviation 2.4 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to codeine or morphine use | 30.9 score on a scale | Standard Deviation 30.4 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to heroin | NA score on a scale | — |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to (lysergic acid diethylamide (LSD) | 5.9 score on a scale | Standard Deviation 5.5 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to phencyclidine (PCP) | 24.0 score on a scale | Standard Deviation 37.3 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to nicotine | 3.6 score on a scale | Standard Deviation 9 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to amphetamine or methamphetamine | 4.6 score on a scale | Standard Deviation 4.8 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to cannabis | 37.4 score on a scale | Standard Deviation 29.6 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to MDMA (Ectasy) | 17.1 score on a scale | Standard Deviation 28.2 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to heroin | NA score on a scale | — |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to benzodiazepine | 66.9 score on a scale | Standard Deviation 38.7 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with caffeine | 4.4 score on a scale | Standard Deviation 9.8 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to mushrooms | 3.8 score on a scale | Standard Deviation 5.7 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with cocaine / | 14.6 score on a scale | Standard Deviation 26.3 |
| Lasmiditan - 200 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to codeine or morphine use | 37.6 score on a scale | Standard Deviation 31.7 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to (lysergic acid diethylamide (LSD) | 7.2 score on a scale | Standard Deviation 8 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to amphetamine or methamphetamine | 4.4 score on a scale | Standard Deviation 6.2 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to nicotine | 4.3 score on a scale | Standard Deviation 8.6 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to heroin | NA score on a scale | — |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to mushrooms | 4.9 score on a scale | Standard Deviation 6.3 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with cocaine / | 12.5 score on a scale | Standard Deviation 23.3 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to phencyclidine (PCP) | 32.3 score on a scale | Standard Deviation 43.7 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to MDMA (Ectasy) | 18.7 score on a scale | Standard Deviation 28.2 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to codeine or morphine use | 45.9 score on a scale | Standard Deviation 32.4 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to benzodiazepine | 74.6 score on a scale | Standard Deviation 31.9 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar to cannabis | 41.7 score on a scale | Standard Deviation 31.6 |
| Lasmiditan - 400 mg | PD: Mean Scores on Drug Similarity VAS Measures | How similar with caffeine | 4.1 score on a scale | Standard Deviation 8.3 |
Secondary
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
Population: All randomized participants who received at least one dose of study drug and had evaluable PD data, and completed the study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Alertness/drowsiness | 42.5 mm | Standard Error 1.97 |
| Placebo | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Agitation/relaxation | 44.1 mm | Standard Error 1.94 |
| Alprazolam - 2 mg | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Alertness/drowsiness | 12.5 mm | Standard Error 1.97 |
| Alprazolam - 2 mg | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Agitation/relaxation | 13.4 mm | Standard Error 1.94 |
| Lasmiditan - 100 mg | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Alertness/drowsiness | 25.6 mm | Standard Error 1.97 |
| Lasmiditan - 100 mg | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Agitation/relaxation | 24.6 mm | Standard Error 1.94 |
| Lasmiditan - 200 mg | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Agitation/relaxation | 22.4 mm | Standard Error 1.94 |
| Lasmiditan - 200 mg | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Alertness/drowsiness | 22.9 mm | Standard Error 1.97 |
| Lasmiditan - 400 mg | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Alertness/drowsiness | 17.7 mm | Standard Error 1.97 |
| Lasmiditan - 400 mg | PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS) | Agitation/relaxation | 15.4 mm | Standard Error 1.94 |
Comparison: Alertness/drowsiness90% CI: [-34, -25.9]
Comparison: Alertness/drowsiness90% CI: [-20.9, -12.8]
Comparison: Alertness/drowsiness90% CI: [-23.6, -15.5]
Comparison: Alertness/drowsiness90% CI: [-28.8, -20.8]
Comparison: Agitation/relaxation90% CI: [-35, -26.5]
Comparison: Agitation/relaxation90% CI: [-23.7, -15.3]
Comparison: Agitation/relaxation90% CI: [-25.9, -17.5]
Comparison: Agitation/relaxation90% CI: [-33, -24.5]
Secondary
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
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan | 132 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 37 |
| Alprazolam - 2 mg | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan | 299 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| Lasmiditan - 100 mg | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan | 689 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
Secondary
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
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PK: Area Under the Curve of Lasmiditan From Zero to Infinity (AUC[0-∞]) | 856 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 32 |
| Alprazolam - 2 mg | PK: Area Under the Curve of Lasmiditan From Zero to Infinity (AUC[0-∞]) | 1810 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 35 |
| Lasmiditan - 100 mg | PK: Area Under the Curve of Lasmiditan From Zero to Infinity (AUC[0-∞]) | 3920 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 28 |