Trial Outcomes & Findings for A Study of the Abuse Potential of Lasmiditan in Participants Who Are Recreational Drug Users (NCT NCT03286218)
NCT ID: NCT03286218
Last Updated: 2020-01-10
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
96 participants
Primary outcome timeframe
Each Phase: 24 Hours
Results posted on
2020-01-10
Participant Flow
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.
Participant milestones
| Measure |
Qualification Phase - Alprazolam Then Placebo Sequence 1
Sequence 1 - One tablet of 1 milligram (mg) alprazolam was administered orally in period 1 then placebo period 2.
|
Qualification Phase - Placebo Then Alprazolam (Alp) Sequence 2
Sequence 2 - Placebo was administered orally period 1 then one tablet of 2 mg alprazolam period 2.
|
Sequence 1
Sequence 1, Periods 1 - 5: (Placebo, 100 mg Las, 2 mg Alp, 200 mg Las, then 400 mg Las)
All participants received:
Period 1: Placebo Period 2: 100 mg Las Period 3: 200 mg Las Period 4: 400 mg Las Period 5: 2 mg Alp
Orally with a 3 day washout between doses.
|
Sequence 2
Sequence 2 , Periods 1 - 5: (100 mg Las, 200 mg Las, Placebo, 400 mg Las, then 2 mg Alp)
All participants received:
Period 1: 100 mg Las Period 2: 200 mg Las Period 3: Placebo Period 4: 400 mg Las Period 5: 2 mg Alp
Orally with a 3 day washout between doses.
|
Sequence 3
Sequence 3, Periods 1 - 5: (200 mg Las, 400 mg Las, 100 mg Las, 2 mg Alp, then Placebo)
All participants received:
Period 1: 200 mg Las Period 2: 400 mg Las Period 3: 100 mg Las Period 4: 2 mg Las Period 5: Placebo
Orally with a 3 day washout between doses.
|
Sequence 4
Sequence 4, Periods 1 - 5: (400 mg Las, 2 mg Alp, 200 mg Las, Placebo, then 100 mg Las)
All participants received:
Period 1: 400 mg Las Period 2: 2 mg Alp Period 3: 200 mg Las Period 4: Placebo Period 5: 100 mg Las
Orally with a 3 day washout between doses.
|
Sequence 5
Sequence 5, Periods 1 - 5: (2 mg Alp, Placebo, 400 mg Las, then 200 mg Las)
All participants received:
Period 1: 2 mg Alp Period 2: Placebo Period 3: 400 mg Las Period 4: 200 mg Las Period 5: 100 mg Las
Orally with a 3 day washout between doses.
|
Sequence 6
Sequence 6, Periods 1 - 5 (400 mg Las, 200 mg Las, 2 mg Alp, 100 mg Las, then Placebo)
All participants received:
Period 1: 400 mg Las Period 2: 200 mg Las Period 3: 2 mg Alp Period 4: 100 mg Las Period 5: Placebo
Orally with a 3 day washout between doses.
|
Sequence 7
Sequence 7, Periods 1-5: (2 mg Alp, 400 mg Las, Placebo, 200 mg Las, then 100 mg Las)
All participants received:
Period 1: 2 mg Alp Period 2: 400 mg Las Period 3: Placebo Period 4: 200 mg Las Period 5: 100 mg Las
Orally with a 3 day washout between doses.
|
Sequence 8
Sequence 8, Periods 1 - 5: Placebo, 2 mg Lap, 100 mg Las, 400 mg Las, then 200 mg Las)
All participants received:
Period 1: Placebo Period 2: 2 mg Las Period 3: 100 mg Las Period 4: 400 mg Las Period 5: 200 mg Las
Orally with a 3 day washout between doses.
|
Sequence 9
Sequence 9, Periods 1 - 5: (100 mg Las, Placebo, 200 mg Las, 2 mg Alp, 400 mg Las)
All participants received:
Period 1: 100 mg Las Period 2: Placebo Period 3: 200 mg Las Period 4: 2 mg Alp Period 5: 400 mg Las
Orally with a 3 day washout between doses.
|
Sequence 10
Sequence 10, Periods 1 - 5: (200 mg Las, 100 mg Las, 400 mg Las, Placebo, then 2 mg Alp)
All participants received:
Period 1: 200 mg Las Period 2: 100 mg Las Period 3: 400 mg Las Period 4: Placebo Period 5: 2 mg Alp
Orally with a 3 day washout between doses.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Qualification Phase Period 1
STARTED
|
48
|
48
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Qualification Phase Period 1
Received at Least One Dose of Study Drug
|
47
|
47
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Qualification Phase Period 1
COMPLETED
|
47
|
47
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Qualification Phase Period 1
NOT COMPLETED
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Qualification Phase Period 2
STARTED
|
47
|
47
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Qualification Phase Period 2
COMPLETED
|
30
|
28
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Qualification Phase Period 2
NOT COMPLETED
|
17
|
19
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Phase Period 1
STARTED
|
0
|
0
|
6
|
6
|
5
|
6
|
6
|
6
|
6
|
6
|
5
|
6
|
|
Treatment Phase Period 1
Received at Least One Dose of Study Drug
|
0
|
0
|
6
|
6
|
5
|
6
|
6
|
6
|
6
|
6
|
5
|
6
|
|
Treatment Phase Period 1
COMPLETED
|
0
|
0
|
5
|
5
|
5
|
5
|
6
|
6
|
6
|
6
|
5
|
5
|
|
Treatment Phase Period 1
NOT COMPLETED
|
0
|
0
|
1
|
1
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Treatment Phase Period 2
STARTED
|
0
|
0
|
5
|
5
|
5
|
5
|
6
|
6
|
6
|
6
|
5
|
5
|
|
Treatment Phase Period 2
COMPLETED
|
0
|
0
|
5
|
5
|
5
|
5
|
6
|
6
|
6
|
6
|
5
|
5
|
|
Treatment Phase Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Phase Period 3
STARTED
|
0
|
0
|
5
|
5
|
5
|
5
|
6
|
6
|
6
|
6
|
5
|
5
|
|
Treatment Phase Period 3
COMPLETED
|
0
|
0
|
5
|
5
|
5
|
5
|
6
|
6
|
6
|
6
|
5
|
5
|
|
Treatment Phase Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Phase Period 4
STARTED
|
0
|
0
|
5
|
5
|
5
|
5
|
6
|
6
|
6
|
6
|
5
|
5
|
|
Treatment Phase Period 4
COMPLETED
|
0
|
0
|
5
|
5
|
5
|
5
|
6
|
6
|
6
|
6
|
5
|
4
|
|
Treatment Phase Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Treatment Phase Period 5
STARTED
|
0
|
0
|
5
|
5
|
5
|
5
|
6
|
6
|
6
|
6
|
5
|
4
|
|
Treatment Phase Period 5
COMPLETED
|
0
|
0
|
5
|
5
|
5
|
5
|
6
|
6
|
6
|
6
|
5
|
4
|
|
Treatment Phase Period 5
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Qualification Phase - Alprazolam Then Placebo Sequence 1
Sequence 1 - One tablet of 1 milligram (mg) alprazolam was administered orally in period 1 then placebo period 2.
|
Qualification Phase - Placebo Then Alprazolam (Alp) Sequence 2
Sequence 2 - Placebo was administered orally period 1 then one tablet of 2 mg alprazolam period 2.
|
Sequence 1
Sequence 1, Periods 1 - 5: (Placebo, 100 mg Las, 2 mg Alp, 200 mg Las, then 400 mg Las)
All participants received:
Period 1: Placebo Period 2: 100 mg Las Period 3: 200 mg Las Period 4: 400 mg Las Period 5: 2 mg Alp
Orally with a 3 day washout between doses.
|
Sequence 2
Sequence 2 , Periods 1 - 5: (100 mg Las, 200 mg Las, Placebo, 400 mg Las, then 2 mg Alp)
All participants received:
Period 1: 100 mg Las Period 2: 200 mg Las Period 3: Placebo Period 4: 400 mg Las Period 5: 2 mg Alp
Orally with a 3 day washout between doses.
|
Sequence 3
Sequence 3, Periods 1 - 5: (200 mg Las, 400 mg Las, 100 mg Las, 2 mg Alp, then Placebo)
All participants received:
Period 1: 200 mg Las Period 2: 400 mg Las Period 3: 100 mg Las Period 4: 2 mg Las Period 5: Placebo
Orally with a 3 day washout between doses.
|
Sequence 4
Sequence 4, Periods 1 - 5: (400 mg Las, 2 mg Alp, 200 mg Las, Placebo, then 100 mg Las)
All participants received:
Period 1: 400 mg Las Period 2: 2 mg Alp Period 3: 200 mg Las Period 4: Placebo Period 5: 100 mg Las
Orally with a 3 day washout between doses.
|
Sequence 5
Sequence 5, Periods 1 - 5: (2 mg Alp, Placebo, 400 mg Las, then 200 mg Las)
All participants received:
Period 1: 2 mg Alp Period 2: Placebo Period 3: 400 mg Las Period 4: 200 mg Las Period 5: 100 mg Las
Orally with a 3 day washout between doses.
|
Sequence 6
Sequence 6, Periods 1 - 5 (400 mg Las, 200 mg Las, 2 mg Alp, 100 mg Las, then Placebo)
All participants received:
Period 1: 400 mg Las Period 2: 200 mg Las Period 3: 2 mg Alp Period 4: 100 mg Las Period 5: Placebo
Orally with a 3 day washout between doses.
|
Sequence 7
Sequence 7, Periods 1-5: (2 mg Alp, 400 mg Las, Placebo, 200 mg Las, then 100 mg Las)
All participants received:
Period 1: 2 mg Alp Period 2: 400 mg Las Period 3: Placebo Period 4: 200 mg Las Period 5: 100 mg Las
Orally with a 3 day washout between doses.
|
Sequence 8
Sequence 8, Periods 1 - 5: Placebo, 2 mg Lap, 100 mg Las, 400 mg Las, then 200 mg Las)
All participants received:
Period 1: Placebo Period 2: 2 mg Las Period 3: 100 mg Las Period 4: 400 mg Las Period 5: 200 mg Las
Orally with a 3 day washout between doses.
|
Sequence 9
Sequence 9, Periods 1 - 5: (100 mg Las, Placebo, 200 mg Las, 2 mg Alp, 400 mg Las)
All participants received:
Period 1: 100 mg Las Period 2: Placebo Period 3: 200 mg Las Period 4: 2 mg Alp Period 5: 400 mg Las
Orally with a 3 day washout between doses.
|
Sequence 10
Sequence 10, Periods 1 - 5: (200 mg Las, 100 mg Las, 400 mg Las, Placebo, then 2 mg Alp)
All participants received:
Period 1: 200 mg Las Period 2: 100 mg Las Period 3: 400 mg Las Period 4: Placebo Period 5: 2 mg Alp
Orally with a 3 day washout between doses.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
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
A Study of the Abuse Potential of Lasmiditan in Participants Who Are Recreational Drug Users
Baseline characteristics by cohort
| Measure |
Overall Participants
n=96 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.
|
|---|---|
|
Age, Continuous
|
31.4 years
STANDARD_DEVIATION 8.6 • n=99 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
77 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
91 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
69 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
96 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Each Phase: 24 HoursPopulation: All randomized participants who received at least one dose of study drug had evaluable PD data in each of the 5 periods.
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.
Outcome measures
| Measure |
Placebo
n=53 Participants
Placebo was administered orally in one of five treatment periods.
|
Alprazolam - 2 mg
n=53 Participants
2 mg of Alprazolam administered orally in one of five treatment periods
|
Lasmiditan - 100 mg
n=53 Participants
100 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
n=53 Participants
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
n=53 Participants
400 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
400 mg of lasmiditan administered orally in one of five treatment periods
|
|---|---|---|---|---|---|---|---|
|
Pharmacodynamics (PD): Maximal Effect Score (Emax) of Bipolar Drug Liking Visual Analog Scale (VAS) Scores
|
53.0 millimeter (mm)
Standard Error 1.94
|
85.4 millimeter (mm)
Standard Error 1.94
|
68.6 millimeter (mm)
Standard Error 1.94
|
73.3 millimeter (mm)
Standard Error 1.94
|
76.6 millimeter (mm)
Standard Error 1.94
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours Post DosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data.
Pharmacokinetics (PK) defined as the maximum observed drug concentration (Cmax) of lasmiditan
Outcome measures
| Measure |
Placebo
n=55 Participants
Placebo was administered orally in one of five treatment periods.
|
Alprazolam - 2 mg
n=55 Participants
2 mg of Alprazolam administered orally in one of five treatment periods
|
Lasmiditan - 100 mg
n=55 Participants
100 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
400 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
400 mg of lasmiditan administered orally in one of five treatment periods
|
|---|---|---|---|---|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan
|
132 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 37
|
299 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 35
|
689 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 34
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours Post DosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data.
PK defined as the area under the curve of lasmiditan from zero to infinity (AUC\[0-∞\])
Outcome measures
| Measure |
Placebo
n=55 Participants
Placebo was administered orally in one of five treatment periods.
|
Alprazolam - 2 mg
n=55 Participants
2 mg of Alprazolam administered orally in one of five treatment periods
|
Lasmiditan - 100 mg
n=55 Participants
100 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
400 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
400 mg of lasmiditan administered orally in one of five treatment periods
|
|---|---|---|---|---|---|---|---|
|
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
|
1810 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 35
|
3920 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 28
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 DosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PD data, and completed the study.
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.
Outcome measures
| Measure |
Placebo
n=53 Participants
Placebo was administered orally in one of five treatment periods.
|
Alprazolam - 2 mg
n=53 Participants
2 mg of Alprazolam administered orally in one of five treatment periods
|
Lasmiditan - 100 mg
n=53 Participants
100 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
n=53 Participants
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
n=53 Participants
400 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
400 mg of lasmiditan administered orally in one of five treatment periods
|
|---|---|---|---|---|---|---|---|
|
PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS)
Overall Drug Liking
|
53.1 mm
Standard Error 2.41
|
86.2 mm
Standard Error 2.41
|
71.7 mm
Standard Error 2.41
|
72.2 mm
Standard Error 2.41
|
77.4 mm
Standard Error 2.41
|
—
|
—
|
|
PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS)
Take Drug Again
|
52.0 mm
Standard Error 2.70
|
86.0 mm
Standard Error 2.70
|
71.1 mm
Standard Error 2.70
|
72.7 mm
Standard Error 2.70
|
77.3 mm
Standard Error 2.70
|
—
|
—
|
|
PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS)
Good Effects
|
10.8 mm
Standard Error 4.10
|
80.5 mm
Standard Error 4.10
|
46.4 mm
Standard Error 4.10
|
62.9 mm
Standard Error 4.10
|
63.8 mm
Standard Error 4.10
|
—
|
—
|
|
PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS)
Bad Effects
|
2.47 mm
Standard Error 3.22
|
22.9 mm
Standard Error 3.22
|
7.51 mm
Standard Error 3.22
|
9.75 mm
Standard Error 3.22
|
15.0 mm
Standard Error 3.22
|
—
|
—
|
|
PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS)
Any Effects
|
8.35 mm
Standard Error 4.05
|
83.7 mm
Standard Error 4.05
|
53.3 mm
Standard Error 4.05
|
65.1 mm
Standard Error 4.05
|
73.2 mm
Standard Error 4.04
|
—
|
—
|
|
PD: Maximal Drug Effects (Emax) Visual Analog Scale (VAS)
High
|
8.61 mm
Standard Error 3.89
|
77.2 mm
Standard Error 3.89
|
43.0 mm
Standard Error 3.89
|
56.1 mm
Standard Error 3.89
|
67.0 mm
Standard Error 3.89
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 DosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PD data, and completed the study.
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.
Outcome measures
| Measure |
Placebo
n=53 Participants
Placebo was administered orally in one of five treatment periods.
|
Alprazolam - 2 mg
n=53 Participants
2 mg of Alprazolam administered orally in one of five treatment periods
|
Lasmiditan - 100 mg
n=53 Participants
100 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
n=53 Participants
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
n=53 Participants
400 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
400 mg of lasmiditan administered orally in one of five treatment periods
|
|---|---|---|---|---|---|---|---|
|
PD: Maximal Drug Effects (Emax) VAS (Hallucinations)
|
0 mm
Interval 0.0 to 0.0
|
0 mm
Interval 0.0 to 1.0
|
0 mm
Interval 0.0 to 0.0
|
0 mm
Interval 0.0 to 0.0
|
0 mm
Interval 0.0 to 0.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 DosePopulation: All randomized participants who received at least one dose of study drug and had evaluable PD data, and completed the study.
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.
Outcome measures
| Measure |
Placebo
n=53 Participants
Placebo was administered orally in one of five treatment periods.
|
Alprazolam - 2 mg
n=53 Participants
2 mg of Alprazolam administered orally in one of five treatment periods
|
Lasmiditan - 100 mg
n=53 Participants
100 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
n=53 Participants
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
n=53 Participants
400 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
400 mg of lasmiditan administered orally in one of five treatment periods
|
|---|---|---|---|---|---|---|---|
|
PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS)
Alertness/drowsiness
|
42.5 mm
Standard Error 1.97
|
12.5 mm
Standard Error 1.97
|
25.6 mm
Standard Error 1.97
|
22.9 mm
Standard Error 1.97
|
17.7 mm
Standard Error 1.97
|
—
|
—
|
|
PD: Minimum Drug Effects (Emin) Visual Analog Scale (VAS)
Agitation/relaxation
|
44.1 mm
Standard Error 1.94
|
13.4 mm
Standard Error 1.94
|
24.6 mm
Standard Error 1.94
|
22.4 mm
Standard Error 1.94
|
15.4 mm
Standard Error 1.94
|
—
|
—
|
SECONDARY outcome
Timeframe: Each Phase: 24 Hours Post DosePopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=95 Participants
Placebo was administered orally in one of five treatment periods.
|
Alprazolam - 2 mg
n=94 Participants
2 mg of Alprazolam administered orally in one of five treatment periods
|
Lasmiditan - 100 mg
n=55 Participants
100 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
n=53 Participants
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
n=55 Participants
400 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 200 mg
n=55 Participants
200 mg of lasmiditan administered orally in one of five treatment periods
|
Lasmiditan - 400 mg
n=55 Participants
400 mg of lasmiditan administered orally in one of five treatment periods
|
|---|---|---|---|---|---|---|---|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar with cocaine /
|
1.3 score on a scale
Standard Deviation 3.5
|
5.8 score on a scale
Standard Deviation 10.6
|
2.2 score on a scale
Standard Deviation 6.6
|
6.1 score on a scale
Standard Deviation 13.6
|
2.7 score on a scale
Standard Deviation 4.2
|
14.6 score on a scale
Standard Deviation 26.3
|
12.5 score on a scale
Standard Deviation 23.3
|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar with caffeine
|
2.9 score on a scale
Standard Deviation 10.3
|
3.2 score on a scale
Standard Deviation 6.0
|
1.5 score on a scale
Standard Deviation 7.2
|
4.4 score on a scale
Standard Deviation 9.7
|
2.2 score on a scale
Standard Deviation 2.4
|
4.4 score on a scale
Standard Deviation 9.8
|
4.1 score on a scale
Standard Deviation 8.3
|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar to MDMA (Ectasy)
|
4.7 score on a scale
Standard Deviation 13.5
|
10.0 score on a scale
Standard Deviation 20.4
|
1.4 score on a scale
Standard Deviation 3.9
|
20.5 score on a scale
Standard Deviation 23.7
|
10.6 score on a scale
Standard Deviation 19.9
|
17.1 score on a scale
Standard Deviation 28.2
|
18.7 score on a scale
Standard Deviation 28.2
|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar to amphetamine or methamphetamine
|
1.5 score on a scale
Standard Deviation 5.4
|
4.3 score on a scale
Standard Deviation 6.3
|
2.4 score on a scale
Standard Deviation 6.0
|
3.9 score on a scale
Standard Deviation 5.5
|
2.3 score on a scale
Standard Deviation 2.5
|
4.6 score on a scale
Standard Deviation 4.8
|
4.4 score on a scale
Standard Deviation 6.2
|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar to phencyclidine (PCP)
|
22.0 score on a scale
Standard Deviation 30.6
|
0.5 score on a scale
Standard Deviation 1.0
|
0.0 score on a scale
Standard Deviation 0.0
|
26.7 score on a scale
Standard Deviation 40.3
|
1.3 score on a scale
Standard Deviation 1.5
|
24.0 score on a scale
Standard Deviation 37.3
|
32.3 score on a scale
Standard Deviation 43.7
|
|
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
|
41.5 score on a scale
Standard Deviation 35.1
|
8.1 score on a scale
Standard Deviation 21.7
|
50.8 score on a scale
Standard Deviation 31.2
|
30.9 score on a scale
Standard Deviation 30.4
|
37.6 score on a scale
Standard Deviation 31.7
|
45.9 score on a scale
Standard Deviation 32.4
|
|
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
|
4.1 score on a scale
Standard Deviation 6.9
|
4.2 score on a scale
Standard Deviation 6.6
|
6.2 score on a scale
Standard Deviation 7.5
|
3.5 score on a scale
Standard Deviation 4.6
|
5.9 score on a scale
Standard Deviation 5.5
|
7.2 score on a scale
Standard Deviation 8.0
|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar to nicotine
|
2.9 score on a scale
Standard Deviation 11.8
|
5.1 score on a scale
Standard Deviation 9.6
|
1.4 score on a scale
Standard Deviation 5.5
|
3.8 score on a scale
Standard Deviation 9.4
|
3.3 score on a scale
Standard Deviation 11.0
|
3.6 score on a scale
Standard Deviation 9.0
|
4.3 score on a scale
Standard Deviation 8.6
|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar to cannabis
|
10.8 score on a scale
Standard Deviation 24.7
|
39.9 score on a scale
Standard Deviation 33.5
|
8.9 score on a scale
Standard Deviation 22.9
|
51.2 score on a scale
Standard Deviation 30.3
|
29.9 score on a scale
Standard Deviation 30.0
|
37.4 score on a scale
Standard Deviation 29.6
|
41.7 score on a scale
Standard Deviation 31.6
|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar to benzodiazepine
|
14.4 score on a scale
Standard Deviation 32.4
|
75.9 score on a scale
Standard Deviation 36.2
|
13.1 score on a scale
Standard Deviation 30.6
|
88.1 score on a scale
Standard Deviation 22.6
|
57.2 score on a scale
Standard Deviation 40.3
|
66.9 score on a scale
Standard Deviation 38.7
|
74.6 score on a scale
Standard Deviation 31.9
|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar to mushrooms
|
0.0 score on a scale
Standard Deviation 0.0
|
2.7 score on a scale
Standard Deviation 3.8
|
2.1 score on a scale
Standard Deviation 5.2
|
3.7 score on a scale
Standard Deviation 6.1
|
2.1 score on a scale
Standard Deviation 2.1
|
3.8 score on a scale
Standard Deviation 5.7
|
4.9 score on a scale
Standard Deviation 6.3
|
|
PD: Mean Scores on Drug Similarity VAS Measures
How similar to heroin
|
0.0 score on a scale
Standard Deviation 0.0
|
17.8 score on a scale
Standard Deviation 38.1
|
NA score on a scale
Standard Deviation NA
Mean and standard deviation are not calculated due to N=2, minimum and maximum values are reported: minimum value is 0 and maximum value is 0.
|
NA score on a scale
Standard Deviation NA
Mean and standard deviation are not calculated due to N=2, minimum and maximum values are reported: minimum value is 0 and maximum value is 79.
|
NA score on a scale
Standard Deviation NA
Mean and standard deviation are not calculated due to N=2, minimum and maximum values are reported: minimum value is 0 and maximum value is 3.
|
NA score on a scale
Standard Deviation NA
Mean and standard deviation are not calculated due to N=2, minimum and maximum values are reported: minimum value is 2 and maximum value is 60.
|
NA score on a scale
Standard Deviation NA
Mean and standard deviation are not calculated due to N=2, minimum and maximum values are reported: minimum value is 2 and maximum value is 96.
|
Adverse Events
Qualification Phase - Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Qualification Phase - Alprazolam
Serious events: 0 serious events
Other events: 74 other events
Deaths: 0 deaths
Treatment Phase - Placebo
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Treatment Phase - 2 mg Alprazolam
Serious events: 0 serious events
Other events: 49 other events
Deaths: 0 deaths
Treatment Phase - 100 mg Lasmiditan
Serious events: 0 serious events
Other events: 33 other events
Deaths: 0 deaths
Treatment Phase - 200 mg Lasmiditan
Serious events: 0 serious events
Other events: 42 other events
Deaths: 0 deaths
Treatment Phase - 400 mg Lasmiditan
Serious events: 0 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Qualification Phase - Placebo
n=95 participants at risk
Placebo was administered orally.
|
Qualification Phase - Alprazolam
n=94 participants at risk
1 mg of alprazolam was administered orally.
|
Treatment Phase - Placebo
n=55 participants at risk
Placebo was administered orally in one of five treatment periods.
|
Treatment Phase - 2 mg Alprazolam
n=53 participants at risk
2 mg alprazolam was administered orally in one of five treatment periods.
|
Treatment Phase - 100 mg Lasmiditan
n=55 participants at risk
100 mg of Lasmiditan was administered orally in one of five treatment periods.
|
Treatment Phase - 200 mg Lasmiditan
n=55 participants at risk
200 mg of Lasmiditan was administered orally in one of five treatment periods.
|
Treatment Phase - 400 mg Lasmiditan
n=55 participants at risk
400 mg of Lasmiditan was administered orally in one of five treatment periods.
|
|---|---|---|---|---|---|---|---|
|
General disorders
Feeling of relaxation
|
3.2%
3/95 • Number of events 3 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
21.3%
20/94 • Number of events 20 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
1.8%
1/55 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
22.6%
12/53 • Number of events 12 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
10.9%
6/55 • Number of events 6 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
7.3%
4/55 • Number of events 4 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
7.3%
4/55 • Number of events 4 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
1.1%
1/95 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/94 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
1.8%
1/55 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/53 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
5.5%
3/55 • Number of events 3 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/55 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
1.8%
1/55 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
|
Nervous system disorders
Amnesia
|
0.00%
0/95 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/94 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/55 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
18.9%
10/53 • Number of events 10 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/55 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
1.8%
1/55 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/55 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/95 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
1.1%
1/94 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/55 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
3.8%
2/53 • Number of events 2 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
5.5%
3/55 • Number of events 3 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
10.9%
6/55 • Number of events 6 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
3.6%
2/55 • Number of events 2 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
0.00%
0/95 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
2.1%
2/94 • Number of events 2 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
7.3%
4/55 • Number of events 5 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
7.5%
4/53 • Number of events 4 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
5.5%
3/55 • Number of events 4 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
5.5%
3/55 • Number of events 3 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
7.3%
4/55 • Number of events 4 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
|
Nervous system disorders
Paraesthesia
|
1.1%
1/95 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/94 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/55 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
1.9%
1/53 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
7.3%
4/55 • Number of events 4 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
10.9%
6/55 • Number of events 6 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
9.1%
5/55 • Number of events 5 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
|
Nervous system disorders
Somnolence
|
3.2%
3/95 • Number of events 3 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
55.3%
52/94 • Number of events 52 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
3.6%
2/55 • Number of events 2 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
84.9%
45/53 • Number of events 45 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
32.7%
18/55 • Number of events 18 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
40.0%
22/55 • Number of events 22 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
54.5%
30/55 • Number of events 30 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
|
Psychiatric disorders
Agitation
|
0.00%
0/95 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/94 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/55 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
9.4%
5/53 • Number of events 5 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
1.8%
1/55 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
5.5%
3/55 • Number of events 3 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
3.6%
2/55 • Number of events 2 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
|
Psychiatric disorders
Euphoric mood
|
1.1%
1/95 • Number of events 1 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
23.4%
22/94 • Number of events 22 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
10.9%
6/55 • Number of events 6 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
43.4%
23/53 • Number of events 23 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
25.5%
14/55 • Number of events 14 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
49.1%
27/55 • Number of events 27 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
45.5%
25/55 • Number of events 25 • From Baseline to Study Completion (Up to 2 months)
All randomized participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60