Healthy
Conditions
Brief summary
The purposes of this study are to evaluate the effect of lasmiditan on blood pressure, as well as to look at the amount of study drug that gets into the blood stream and how long it takes the body to get rid of it in healthy elderly participants. The tolerability of the study drug will also be evaluated. Information about any side effects that may occur will also be collected. This study will take about 11 days, not including screening. Screening is required within 28 days prior to the start of the study.
Interventions
DRUGPlacebo
Administered orally.
DRUGLasmiditan
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
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy males or females, as determined through medical history and physical examination * Have a body mass index (BMI) of 19.0 to 35.0 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. * Are persons who have previously received lasmiditan. * Have a history of, or electrocardiogram (ECG) findings of, clinically significant bradycardia, heart block, tachy or brady arrhythmias, or have any other abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study. * Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data. appendectomy, splenectomy, and cholecystectomy are considered as acceptable. * Show a history of central nervous system (CNS) conditions such as strokes, transient ischemic attacks, significant head trauma, seizures, CNS infections, migraines, brain surgery, or any other neurological conditions that, in the opinion of the investigator, increase the risk of participating in the study. * Show evidence of active renal disease (e.g. diabetic renal disease, polycystic kidney disease) or estimated glomerular filtration rate \<60 milliliters per minute per 1.73 meter squared (mL/min/m²). * Have a history of syncope, presyncopy, uncontrolled vertigo, postural dizziness, or at risk for falls, as judged to be clinically significant by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics: Change From Baseline in Peak Hourly Mean Values of Systolic Blood Pressure (SBP) | Baseline through 24 hours after each administration of study drug | Mean 24-hour systolic blood pressure (SBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using linear mixed effects model adjusting for baseline, treatment, treatment sequence, period, treatment by time point interaction, and a random effect of participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours, postdose | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan. |
| PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours, postdose | PK: Area under the Concentration Versus Time Curve from Zero to Infinity (AUC\[0-∞\]) of Lasmiditan. |
Countries
United States
Participant flow
Pre-assignment details
Crossover study with three study periods, each participant received single oral doses of Lasmiditan 200 milligrams (mg), Lasmiditan 100 mg and Placebo tablets as per the dosing sequence in each period. The washout period between dosing in consecutive study periods was at least 48 hours.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Participants received Lasmiditan (200 milligrams (mg) and 100mg) and placebo tablets as per the below dosing schedule.
Period 1: Lasmiditan 200 mg, Period 2: Lasmiditan 100 mg and Period 3: Placebo | 6 |
| Sequence 2 Participants received Lasmiditan (200 milligrams (mg) and 100mg) and placebo tablets as per the below dosing schedule.
Period 1: Lasmiditan 100 mg, Period 2: Placebo and Period 3: Lasmiditan 200 mg | 6 |
| Sequence 3 Participants received Lasmiditan (200 milligrams (mg) and 100mg) and placebo tablets as per the below dosing schedule.
Period 1: Placebo, Period 2: Lasmiditan 200 mg and Period 3: Lasmiditan 100 mg | 6 |
| Sequence 4 Participants received Lasmiditan (200 milligrams (mg) and 100mg) and placebo tablets as per the below dosing schedule.
Period 1: Placebo, Period 2: Lasmiditan 100 mg and Period 3: Lasmiditan 200 mg | 6 |
| Sequence 5 Participants received Lasmiditan (200 milligrams (mg) and 100mg) and placebo tablets as per the below dosing schedule.
Period 1: Lasmiditan 200 mg, Period 2: Placebo and Period 3: Lasmiditan 100 mg | 6 |
| Sequence 6 Participants received Lasmiditan (200 milligrams (mg) and 100mg) and placebo tablets as per the below dosing schedule.
Period 1: Lasmiditan 100 mg, Period 2: Lasmiditan 200 mg and Period 3: Placebo | 6 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Sequence 4 | Sequence 5 | Sequence 6 | Total | Sequence 1 | Sequence 2 | Sequence 3 |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 6 Participants | 6 Participants | 34 Participants | 5 Participants | 5 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 6 Participants | 33 Participants | 6 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 5 Participants | 34 Participants | 5 Participants | 6 Participants | 6 Participants |
| Region of Enrollment United States | 6 Participants | 6 Participants | 6 Participants | 36 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 4 Participants | 15 Participants | 2 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 2 Participants | 21 Participants | 4 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 15 / 36 | 6 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 36 | 0 / 35 | 0 / 35 |
Outcome results
Primary
Pharmacodynamics: Change From Baseline in Peak Hourly Mean Values of Systolic Blood Pressure (SBP)
Mean 24-hour systolic blood pressure (SBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using linear mixed effects model adjusting for baseline, treatment, treatment sequence, period, treatment by time point interaction, and a random effect of participant.
Time frame: Baseline through 24 hours after each administration of study drug
Population: All randomized participants who received at least one dose of study drug and have data for SBP
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lasmiditan 200 mg | Pharmacodynamics: Change From Baseline in Peak Hourly Mean Values of Systolic Blood Pressure (SBP) | 15.79 millimeters of mercury (mmHg) | Standard Error 1.774 |
| Lasmiditan 100 mg | Pharmacodynamics: Change From Baseline in Peak Hourly Mean Values of Systolic Blood Pressure (SBP) | 15.50 millimeters of mercury (mmHg) | Standard Error 1.82 |
| Placebo | Pharmacodynamics: Change From Baseline in Peak Hourly Mean Values of Systolic Blood Pressure (SBP) | 17.14 millimeters of mercury (mmHg) | Standard Error 1.797 |
p-value: <0.000195% CI: [-1000, 1.81]Linear Mixed Effects Model
p-value: <0.000195% CI: [-1000, 2.06]Linear Mixed Effects Model
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours, postdose
Population: All randomized participants who received at least one dose of study drug and have evaluable pharmacokinetics (PK) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasmiditan 200 mg | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan | 159 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| Lasmiditan 100 mg | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan | 339 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
Secondary
PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan
PK: Area under the Concentration Versus Time Curve from Zero to Infinity (AUC\[0-∞\]) of Lasmiditan.
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours, postdose
Population: All randomized participants who received at least one dose of study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lasmiditan 200 mg | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan | 1170 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 34 |
| Lasmiditan 100 mg | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Lasmiditan | 2470 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 35 |