Healthy
Conditions
Brief summary
This study will assess the safety, tolerability and blood concentrations of lasmiditan and topiramate together compared to lasmiditan and topiramate separately. Information about any side effects that may occur will be collected. Participants will be admitted to the Clinical Research Unit (CRU) one day prior to the start of the study and will remain through Day 14. This study is expected to last approximately 25 days, not including screening. Screening is required within 28 days prior to the start of the study.
Interventions
DRUGLasmiditan
Administered orally
DRUGPlacebo
Administered orally
DRUGTopiramate
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are healthy males or females (of non-child bearing potential), as determined by medical history and physical examination * Have a body mass index of 19.0 to 35.0 kilograms per meter squared (kg/m²) inclusive
Exclusion criteria
* Have known allergies to lasmiditan, topiramate, related compounds or any components of the formulation of lasmiditan or topiramate * Have an abnormal supine blood pressure, defined as systolic blood pressure less than (\<) 90 or great (\>) 140 millimeters of mercury (mmHg) or diastolic blood pressure \<60 or \>90 mmHg at screening * Have known or ongoing psychiatric disorders considered clinically significant by the investigator or demonstrate suicidal ideation on the Columbia Suicide Severity Rating Scale (C-SSRS) * Have a clinically significant abnormality in the neurological examination * Have current or a history of orthostatic hypotension (\>20-mmHg drop in systolic blood pressure, or \>10-mmHg drop in diastolic blood pressure) with or without dizziness and/or syncope at screening or admission to the Clinical Research Unit (CRU) upon repeat testing * Have an estimated glomerular filtration rate using Modification of Diet in Renal Disease \<60 milliliter per minute (mL/min) per 1.73 meter squared (m²) * Have a history of glaucoma * Have a history of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
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 through Day 24 | A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14 | Day 13 and Day 14: predose,0.5,1,1.5,2,3,4,6,8,12 hours(h) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Topiramate when administered alone on Day 13 and when coadministered with lasmiditan on Day 14 |
| PK: Maximum Observed Drug Concentration (Cmax) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14 | Day 1 and Day 14: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours | PK: Maximum Observed Drug Concentration (Cmax) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14 |
| PK: Area Under the Plasma Concentration Versus Time Curve During One Dosing Interval (AUC [Tau]) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14 | Day 13 and Day 14 - predose,0.5,1,1.5,2,3,4,6,8,12 hours(h) | PK: Area Under the Plasma Concentration versus Time Curve During One Dosing Interval (AUC \[tau\]) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14 |
| PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity AUC(0-∞) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14 | Day 1 and Day 14: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours | PK: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity AUC(0-∞) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence 1: 50 mg Topiramate + Placebo Placebo film-coated tablets administered orally once in the morning of Day 1 and once in the morning of Day 14.
Two oral doses of 50 mg (2 × 25-mg tablets) separated by approximately 12 hours on Days 8 to 13. | 10 |
| Treatment Sequence 2: 50 mg Topiramate + 200 mg Lasmiditan 200 mg lasmiditan film-coated tablet administered orally once in the morning of Day 1 and once in the morning of Day 14.
Two oral doses of 50 mg (2 × 25-mg tablets) separated by approximately 12 hours on Days 8 to 13. | 20 |
| Total | 30 |
Baseline characteristics
| Characteristic | Treatment Sequence 1: 50 mg Topiramate + Placebo | Total | Treatment Sequence 2: 50 mg Topiramate + 200 mg Lasmiditan |
|---|---|---|---|
| Age, Continuous | 44.3 years STANDARD_DEVIATION 13.3 | 44.1 years STANDARD_DEVIATION 13.3 | 44.0 years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 29 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 11 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 17 Participants | 8 Participants |
| Region of Enrollment United States | 10 Participants | 30 Participants | 20 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 10 Participants | 29 Participants | 19 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 10 | 0 / 30 | 0 / 20 | 0 / 10 |
| other Total, other adverse events | 8 / 20 | 3 / 10 | 5 / 30 | 8 / 20 | 2 / 10 |
| serious Total, serious adverse events | 0 / 20 | 0 / 10 | 0 / 30 | 0 / 20 | 0 / 10 |
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
A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline through Day 24
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | 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 | 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 |
| Topiramate Alone | 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 Topiramate + 200 mg Lasmiditan | 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 Topiramate + Placebo | 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): Maximum Observed Drug Concentration (Cmax) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Topiramate when administered alone on Day 13 and when coadministered with lasmiditan on Day 14
Time frame: Day 13 and Day 14: predose,0.5,1,1.5,2,3,4,6,8,12 hours(h)
Population: All participants who received at least one dose of lasmiditan or topiramate and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14 | 4300 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 15 |
| 200 mg Lasmiditan | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14 | 4190 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 16 |
Secondary
PK: Area Under the Plasma Concentration Versus Time Curve During One Dosing Interval (AUC [Tau]) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14
PK: Area Under the Plasma Concentration versus Time Curve During One Dosing Interval (AUC \[tau\]) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14
Time frame: Day 13 and Day 14 - predose,0.5,1,1.5,2,3,4,6,8,12 hours(h)
Population: All participants who received at least one dose of lasmiditan or topiramate and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PK: Area Under the Plasma Concentration Versus Time Curve During One Dosing Interval (AUC [Tau]) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14 | 42600 nanograms*hour per milliliter(ng*h/mL) | Geometric Coefficient of Variation 15 |
| 200 mg Lasmiditan | PK: Area Under the Plasma Concentration Versus Time Curve During One Dosing Interval (AUC [Tau]) of Topiramate When Administered Alone on Day 13 and When Coadministered With Lasmiditan on Day 14 | 42800 nanograms*hour per milliliter(ng*h/mL) | Geometric Coefficient of Variation 17 |
Secondary
PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity AUC(0-∞) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14
PK: Area Under the Plasma Concentration versus Time Curve From Zero to Infinity AUC(0-∞) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14
Time frame: Day 1 and Day 14: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours
Population: All participants who received at least one dose of lasmiditan or topiramate and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity AUC(0-∞) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14 | 1860 nanograms*hour per milliliter(ng*h/mL) | Geometric Coefficient of Variation 29 |
| 200 mg Lasmiditan | PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity AUC(0-∞) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14 | 2050 nanograms*hour per milliliter(ng*h/mL) | Geometric Coefficient of Variation 29 |
Secondary
PK: Maximum Observed Drug Concentration (Cmax) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14
PK: Maximum Observed Drug Concentration (Cmax) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14
Time frame: Day 1 and Day 14: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours
Population: All participants who received at least one dose of lasmiditan or topiramate and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PK: Maximum Observed Drug Concentration (Cmax) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14 | 276 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| 200 mg Lasmiditan | PK: Maximum Observed Drug Concentration (Cmax) of Lasmiditan When Administered Alone on Day 1 and When Coadministered With Topiramate on Day 14 | 301 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 35 |