Migraine Disorders
Conditions
Brief summary
The purpose of this study is to measure how much of the drug gets into the blood stream and how long it takes the body to get rid of it during an acute migraine attack and also during the time between acute migraine attacks. Information about any side effects that may occur will also be collected. This study includes two study periods. Each study period requires an overnight stay in the Clinical Research Unit (CRU) for at least one night (and up to three nights), followed by up to two outpatient appointments. This study will last approximately 5-6 weeks (not including screening). Follow-up is required four to seven days after last dose of investigational drug. Screening is required within 28 days prior to the start of the study. This study is for research purposes only and is not intended to treat any medical condition.
Interventions
DRUGLasmiditan
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Multi-center, open-label study with 2 study periods.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Males or females with history of migraine with or without aura, as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.1 and 1.2) (ICHD-3 beta, Cephalalgia 2013), for at least 1 year, based on medical history * Have a body mass index (BMI) of 18.0 to 40.0 kilograms per meter squared (kg/m²) inclusive, at the time of screening
Exclusion criteria
* Have known allergies to lasmiditan, related compounds, or any components of the formulation of lasmiditan * Have participated, within the last 30 days, in a clinical study involving an investigational product. If the previous investigational product has a long half-life, 5 half-lives or 30 days (whichever is longer) should have passed * Have an abnormal blood pressure, defined as systolic blood pressure less than or equal to (≤) 90 or greater than (\>) 155 millimeters of mercury (mmHg) or diastolic blood pressure ≤ to 50 or \>95 mmHg * Have clinically significant electrocardiogram (ECG) findings, including a QT interval corrected for heart rate using QT interval corrected for heart rate using Fridericia's formula (QTcF) value \>450 milliseconds (ms) (males) or \>470 ms (females), clinically significant bradycardia, cardiac block, or bradyarrhythmias * Have a history of, show evidence of, or are undergoing treatment for significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, major depressive disorder) * Have a history of gastrointestinal surgery, or a history of or current irritable bowel syndrome, mal-absorptive disorders, or other gastrointestinal motility disorders. Appendectomy, splenectomy, and cholecystectomy are considered as acceptable * Have used or intend to use any migraine prevention treatments (including, but not limited to, propranolol or topiramate) within 30 days prior to dosing and until the follow-up visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8,12, 18, 24, 48, and 72h post-dose | PK: Cmax of Lasmiditan in Each Period. |
| PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8,12, 18, 24, 48, and 72h post-dose | PK: AUC(0-∞) of Lasmiditan in Each Period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, and 72h post-dose | PK: Cmax of Major Lasmiditan Metabolites \[M3, M8, M7, (S,R)-M18and (S,S)-M18\] in Each Period. |
| PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, and 72h post-dose | PK: AUC(0-∞) of Major Lasmiditan Metabolites \[M3, M8, M7, (S,R)-M18and (S,S)-M18\] in Each Period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lasmiditan Participants were administered a single oral dose of 200 mg lasmiditan tablet on 2 occasions (Day 1 of each period) during a migraine attack (Period 1) and during their inter-ictal period (Period 2). | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Lasmiditan |
|---|---|
| Age, Continuous | 40.8 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 16 / 16 | 12 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period
PK: Cmax of Lasmiditan in Each Period.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8,12, 18, 24, 48, and 72h post-dose
Population: All enrolled participants who received at least one dose of study drug and have evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasmiditan (Period 1) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 233 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| Lasmiditan (Period 2) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan in Each Period | 227 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
Primary
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.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8,12, 18, 24, 48, and 72h post-dose
Population: All enrolled participants who received at least one dose of study drug and have evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasmiditan (Period 1) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 1570 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 43 |
| Lasmiditan (Period 2) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan in Each Period | 1640 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 46 |
Secondary
PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period
PK: AUC(0-∞) of Major Lasmiditan Metabolites \[M3, M8, M7, (S,R)-M18and (S,S)-M18\] in Each Period.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, and 72h post-dose
Population: All enrolled participants who received at least one dose of study drug and have evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lasmiditan (Period 1) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M8 | 6180 ng*h/mL | Geometric Coefficient of Variation 28 |
| Lasmiditan (Period 1) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: (S,R)-M18 | 1460 ng*h/mL | Geometric Coefficient of Variation 33 |
| Lasmiditan (Period 1) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M7 | 820 ng*h/mL | Geometric Coefficient of Variation 80 |
| Lasmiditan (Period 1) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: (S,S)-M18 | 363 ng*h/mL | Geometric Coefficient of Variation 29 |
| Lasmiditan (Period 1) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M3 | 68.0 ng*h/mL | Geometric Coefficient of Variation 44 |
| Lasmiditan (Period 2) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: (S,S)-M18 | 318 ng*h/mL | Geometric Coefficient of Variation 24 |
| Lasmiditan (Period 2) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M3 | 77.8 ng*h/mL | Geometric Coefficient of Variation 33 |
| Lasmiditan (Period 2) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M8 | 6380 ng*h/mL | Geometric Coefficient of Variation 27 |
| Lasmiditan (Period 2) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M7 | 949 ng*h/mL | Geometric Coefficient of Variation 60 |
| Lasmiditan (Period 2) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: (S,R)-M18 | 1570 ng*h/mL | Geometric Coefficient of Variation 34 |
Secondary
PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period
PK: Cmax of Major Lasmiditan Metabolites \[M3, M8, M7, (S,R)-M18and (S,S)-M18\] in Each Period.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, and 72h post-dose
Population: All enrolled participants who received at least one dose of study drug and have evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Lasmiditan (Period 1) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M8 | 319 ng/mL | Geometric Coefficient of Variation 34 |
| Lasmiditan (Period 1) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: (S,R)-M18 | 57.0 ng/mL | Geometric Coefficient of Variation 31 |
| Lasmiditan (Period 1) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M7 | 77.2 ng/mL | Geometric Coefficient of Variation 52 |
| Lasmiditan (Period 1) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: (S,S)-M18 | 14.0 ng/mL | Geometric Coefficient of Variation 37 |
| Lasmiditan (Period 1) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M3 | 14.5 ng/mL | Geometric Coefficient of Variation 54 |
| Lasmiditan (Period 2) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: (S,S)-M18 | 15.0 ng/mL | Geometric Coefficient of Variation 27 |
| Lasmiditan (Period 2) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M3 | 14.8 ng/mL | Geometric Coefficient of Variation 41 |
| Lasmiditan (Period 2) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M8 | 326 ng/mL | Geometric Coefficient of Variation 30 |
| Lasmiditan (Period 2) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: M7 | 85.9 ng/mL | Geometric Coefficient of Variation 42 |
| Lasmiditan (Period 2) | PK: Maximum Observed Drug Concentration (Cmax) of Major Lasmiditan Metabolites [M3, M8, M7, (S,R)-M18and (S,S)-M18] in Each Period | Metabolite: (S,R)-M18 | 59.5 ng/mL | Geometric Coefficient of Variation 34 |