Healthy
Conditions
Brief summary
The main purpose of this study is to evaluate the safety and tolerability of lasmiditan in healthy Japanese and Caucasian participants. The study will also investigate how much lasmiditan gets into the bloodstream and how long it takes the body to get rid of lasmiditan when given to Japanese and Caucasians. The study will last up to 47 days for each participant.
Interventions
DRUGLasmiditan
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
20 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy Japanese (first generation) or Caucasian males or females, as determined by medical history and physical examination * Have a body mass index of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive
Exclusion criteria
* Have known allergies to lasmiditan, related compounds or any components of the formulation of lasmiditan * Have previously received the investigational product in this study, withdrawn from this study, or received lasmiditan in any other study investigating lasmiditan * Have an abnormal supine blood pressure at screening. * Have a history of syncope, presyncope, uncontrolled vertigo, postural dizziness, or a risk of falls, as judged to be clinically significant by the investigator, or have orthostatic decreases in supine blood pressure of \>20 millimeters of mercury (mmHg), or have orthostatic decreases in diastolic blood pressure of \>10 mmHg at screening. * Are women who are pregnant, lactating, or have a positive pregnancy test at screening or admission to the clinical research unit (CRU) * Have donated blood of more than 500 milliliters (mL) within 1 month prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline up to Day 20 | The number of participants with 1 or more SAEs considered by the investigator to be related to study drug administration is reported. Summaries of SAEs and other non-serious adverse events (AEs), regardless of causality, are located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | Period 1 and Period 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose; Period 3: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 36 and 48 hours postdose | PK: AUC(0-∞) of Lasmiditan in Each Period was evaluated. |
| PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | Period 1 and Period 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose; Period 3: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 36 and 48 hours postdose | PK: Cmax of Lasmiditan in Each Period was evaluated. |
Countries
United States
Participant flow
Pre-assignment details
Crossover study with three study periods, each participant received single/repeated oral doses of 50, 100, 200, 400, or 2 X 200 milligram (mg) lasmiditan, placebo, or 2 X placebo, according to their assigned treatment sequence, on Day 1 of each Period. The washout period between dosing in consecutive study periods was approximately 72 hours.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Sequence 1: Japanese Participants received single oral doses of Lasmiditan and placebo on day 1 of each treatment period as per the below dosing sequence.
Period 1: Placebo Period 2: 100 mg Lasmiditan and Period 3: 200 mg Lasmiditan. | 3 |
| Cohort 1: Sequence 2: Japanese Participants received single oral doses of Lasmiditan and placebo on day 1 of each treatment period as per the below dosing sequence.
Period 1: 50 mg Lasmiditan Period 2: Placebo and Period 3: 200 mg Lasmiditan. | 2 |
| Cohort 1: Sequence 3: Japanese Participants received single oral doses of Lasmiditan and placebo on day 1 of each treatment period as per the below dosing sequence.
Period 1: 50 mg Lasmiditan Period 2: 100 mg Lasmiditan and Period 3: Placebo. | 2 |
| Cohort 2: Sequence 1: Japanese Participants received single oral doses of Lasmiditan and placebo on day 1 of each treatment period as per the below dosing sequence.
Period 1: Placebo Period 2: 400 mg Lasmiditan and Period 3: 2 X 200 mg Lasmiditan (2 single doses administered 2 hours apart). | 2 |
| Cohort 2: Sequence 2: Japanese Participants received single oral doses of Lasmiditan and placebo on day 1 of each treatment period as per the below dosing sequence.
Period 1: 50 mg Lasmiditan Period 2: Placebo and Period 3: 2 X 200 mg Lasmiditan (2 single doses administered 2 hours apart). | 2 |
| Cohort 2: Sequence 3: Japanese Participants received single oral doses of Lasmiditan and placebo on day 1 of each treatment period as per the below dosing sequence.
Period 1: 100 mg Lasmiditan Period 2: 400 mg Lasmiditan and Period 3: 2 X Placebo (2 single doses administered 2 hours apart). | 2 |
| Cohort 2: Sequence 4: Japanese Participants received single oral doses of Lasmiditan on day 1 of each treatment period as per the below dosing sequence.
Period 1: 200 mg Lasmiditan Period 2: 400 mg Lasmiditan and Period 3: 2 X 200 mg Lasmiditan (2 single doses administered 2 hours apart). | 3 |
| Cohort 3: Sequence 1: Caucasian Participants received single oral doses of Lasmiditan and placebo on day 1 of each treatment period as per the below dosing sequence.
Period 1: Placebo Period 2: 100 mg Lasmiditan and Period 3: 200 mg Lasmiditan. | 3 |
| Cohort 3: Sequence 2: Caucasian Participants received single oral doses of Lasmiditan and placebo on day 1 of each treatment period as per the below dosing sequence.
Period 1: 50 mg Lasmiditan Period 2: Placebo and Period 3: 200 mg Lasmiditan. | 3 |
| Cohort 3: Sequence 3: Caucasian Participants received single oral doses of Lasmiditan and placebo on day 1 of each treatment period as per the below dosing sequence.
Period 1: 50 mg Lasmiditan Period 2: 100 mg Lasmiditan and Period 3: Placebo. | 2 |
| Cohort 3: Sequence 4: Caucasian Participants received single oral doses of Lasmiditan on day 1 of each treatment period as per the below dosing sequence.
Period 1: 50 mg Lasmiditan Period 2: 100 mg Lasmiditan and Period 3: 200 mg Lasmiditan . | 3 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 2 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 1: Sequence 2: Japanese | Cohort 1: Sequence 3: Japanese | Cohort 2: Sequence 1: Japanese | Cohort 2: Sequence 2: Japanese | Cohort 2: Sequence 3: Japanese | Cohort 2: Sequence 4: Japanese | Cohort 1: Sequence 1: Japanese | Cohort 3: Sequence 1: Caucasian | Cohort 3: Sequence 2: Caucasian | Cohort 3: Sequence 3: Caucasian | Cohort 3: Sequence 4: Caucasian |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 27 participants | 2 participants | 2 participants | 2 participants | 2 participants | 2 participants | 3 participants | 3 participants | 3 participants | 3 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 13 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 14 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 2 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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 | 0 / 2 | 0 / 6 | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 6 / 10 | 0 / 8 | 0 / 2 | 2 / 6 | 4 / 8 | 5 / 7 | 3 / 8 | 6 / 8 | 3 / 9 | 6 / 7 | 5 / 7 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 | 0 / 2 | 0 / 6 | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 7 | 0 / 7 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
The number of participants with 1 or more SAEs considered by the investigator to be related to study drug administration is reported. Summaries of SAEs and other non-serious adverse events (AEs), regardless of causality, are located in the Reported Adverse Events module.
Time frame: Baseline up to Day 20
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: Japanese | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Placebo: Caucasian | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 2 x Placebo: Japanese | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 50 mg Lasmiditan: Japanese | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 50 mg Lasmiditan: Caucasian | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 100 mg Lasmiditan: Japanese | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 100 mg Lasmiditan: Caucasian | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 200 mg Lasmiditan: Japanese | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 200 mg Lasmiditan: Caucasian | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 400 mg Lasmiditan: Japanese | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 2 X 200 mg Lasmiditan: Japanese | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period
PK: AUC(0-∞) of Lasmiditan in Each Period was evaluated.
Time frame: Period 1 and Period 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose; Period 3: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 36 and 48 hours postdose
Population: All enrolled participants who received at least one dose of study drug and have evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: Japanese | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 362 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 46 |
| Placebo: Caucasian | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 366 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 78 |
| 2 x Placebo: Japanese | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 791 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 22 |
| 50 mg Lasmiditan: Japanese | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 826 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 70 |
| 50 mg Lasmiditan: Caucasian | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 1540 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 26 |
| 100 mg Lasmiditan: Japanese | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 2120 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 50 |
| 100 mg Lasmiditan: Caucasian | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 3780 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 32 |
| 200 mg Lasmiditan: Japanese | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 3500 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 26 |
Secondary
PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period
PK: Cmax of Lasmiditan in Each Period was evaluated.
Time frame: Period 1 and Period 2: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose; Period 3: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 36 and 48 hours postdose
Population: All enrolled participants who received at least one dose of study drug and have evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: Japanese | PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 54.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| Placebo: Caucasian | PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 52.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 84 |
| 2 x Placebo: Japanese | PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 122 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| 50 mg Lasmiditan: Japanese | PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 101 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 94 |
| 50 mg Lasmiditan: Caucasian | PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 249 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
| 100 mg Lasmiditan: Japanese | PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 309 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| 100 mg Lasmiditan: Caucasian | PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 680 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| 200 mg Lasmiditan: Japanese | PK: Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 519 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |