Healthy
Conditions
Brief summary
The purpose of this study is to assess whether taking lasmiditan and sumatriptan together will have any additional effects on heart rate and blood pressure compared to taking lasmiditan and sumatriptan individually. This study will also 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 when these two drugs are taken together. This study will last about 21 days, not including the screening. Participants will spend 16 days/15 nights in the clinical research unit (CRU) followed by follow-up. Screening is required within 28 days prior to the start of the study.
Interventions
DRUGLasmiditan
Administered orally
DRUGSumatriptan
Administered orally
DRUGPlacebo for Lasmiditan
Administered orally
DRUGPlacebo for Sumatriptan
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
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy males or females, 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, Sumatriptan, related compounds, or any components of the formulations of Lasmiditan and Sumatriptan * Have a history of, or electrocardiogram (ECG) findings of, clinically significant bradycardia, heart block, tachy or brady arrhythmias * Have a history, signs, or symptoms of arrhythmia or Wolff Parkinson White syndrome that could affect the participant's safety * Have an estimated glomerular filtration rate (eGFR) of less than (\<) 60 milliliter per minute (mL/min) per 1.73 m² * Have a resting systolic blood pressure (SBP) greater than (\>) 135 millimeters of mercury (mmHg) and diastolic blood pressure (DBP) \>85 mmHg at screening * Have a supine pulse rate (PR) of \<50 or \>90 beats per minute (bpm) at screening * Have a history, signs, or symptoms of vasospastic coronary artery disease * Have known or ongoing neuropsychiatric disorders (for example, manic depressive illness, schizophrenia, depression) considered as clinically significant by the investigator * Use of monoamine oxidase-A inhibitors and other drugs associated with serotonin within the 3 months prior to the first dosing occasion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) | Baseline (Day 1), Day 2 | 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) mean peak changes from baseline were calculated using a linear mixed-effects model with baseline, treatment, period, and sequence as fixed effects and participant as a random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan and Sumatriptan | Lasmiditan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12 , 24 ,36 and 48 hours(h) postdose; Sumatriptan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12 and 24 h postdose | PK: Cmax of Lasmiditan and Sumatriptan was evaluated. |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0 ∞]) of Lasmiditan and Sumatriptan | Lasmiditan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12, 24 ,36 and 48 h postdose; Sumatriptan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12 and 24 h postdose | PK: AUC(0 ∞) of Lasmiditan and Sumatriptan was evaluated. |
Countries
United States
Participant flow
Pre-assignment details
Crossover study with four periods. Participants were randomized to one of four treatment (Treatment A: 200 milligram (mg) lasmiditan + 100mg sumatriptan, Treatment B: 200mg lasmiditan + placebo, Treatment C: 100mg sumatriptan + placebo, Treatment D: placebo + placebo) period sequences. There was a washout of at least 4 days between each dosing day.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants received single oral dose of 200 mg lasmiditan, 100 mg sumatriptan, 200 mg lasmiditan + 100 mg sumatriptan or placebo tablets on Day 1 of each treatment period according to their assigned treatment sequence. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 40.1 years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 40 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 39 | 0 / 39 | 0 / 40 |
| other Total, other adverse events | 4 / 39 | 7 / 39 | 3 / 39 | 1 / 40 |
| serious Total, serious adverse events | 0 / 39 | 0 / 39 | 0 / 39 | 0 / 40 |
Outcome results
Primary
Pharmacodynamics (PD): Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP)
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) mean peak changes from baseline were calculated using a linear mixed-effects model with baseline, treatment, period, and sequence as fixed effects and participant as a random effect.
Time frame: Baseline (Day 1), Day 2
Population: All enrolled participants who received at least one dose of study drug with evaluable blood pressure data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 200 mg Lasmiditan + 100 mg Sumatriptan (A): | Pharmacodynamics (PD): Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) | 13.81 Millimeters of mercury (mmHg) |
| 200 mg Lasmiditan + Placebo (B) | Pharmacodynamics (PD): Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) | 12.17 Millimeters of mercury (mmHg) |
| 100 mg Sumatriptan + Placebo (C) | Pharmacodynamics (PD): Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) | 13.63 Millimeters of mercury (mmHg) |
| Placebo + Placebo (D) | Pharmacodynamics (PD): Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) | 11.42 Millimeters of mercury (mmHg) |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0 ∞]) of Lasmiditan and Sumatriptan
PK: AUC(0 ∞) of Lasmiditan and Sumatriptan was evaluated.
Time frame: Lasmiditan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12, 24 ,36 and 48 h postdose; Sumatriptan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12 and 24 h 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 |
|---|---|---|---|
| 200 mg Lasmiditan + 100 mg Sumatriptan (A): | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0 ∞]) of Lasmiditan and Sumatriptan | 2110 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| 200 mg Lasmiditan + Placebo (B) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0 ∞]) of Lasmiditan and Sumatriptan | 2170 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 33 |
| 100 mg Sumatriptan + Placebo (C) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0 ∞]) of Lasmiditan and Sumatriptan | 253 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| Placebo + Placebo (D) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0 ∞]) of Lasmiditan and Sumatriptan | 240 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
Secondary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan and Sumatriptan
PK: Cmax of Lasmiditan and Sumatriptan was evaluated.
Time frame: Lasmiditan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12 , 24 ,36 and 48 hours(h) postdose; Sumatriptan: Predose, 0.5, 1, 1.5,2, 2.5, 3, 4, 6, 8, 12 and 24 h 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 |
|---|---|---|---|
| 200 mg Lasmiditan + 100 mg Sumatriptan (A): | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan and Sumatriptan | 304 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
| 200 mg Lasmiditan + Placebo (B) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan and Sumatriptan | 328 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| 100 mg Sumatriptan + Placebo (C) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan and Sumatriptan | 56.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
| Placebo + Placebo (D) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan and Sumatriptan | 50.7 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 42 |