Healthy
Conditions
Brief summary
This study will evaluate the effect of food on the pharmacokinetics (PK) of a single dose of lasmiditan in healthy participants.
Detailed description
An open-label, cross-over, two-period, randomized, sequential study in order to investigate the effect of food on the pharmacokinetics of lasmiditan 200 mg. Two single doses of lasmiditan will be administered with the participants in fed and fasted states.
Interventions
DRUGLasmiditan
2 discrete doses separated by 6 days.
Sponsors
CoLucid Pharmaceuticals
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female aged 18-50 years. * Able and willing to give written informed consent. * Females of child bearing potential must be using or willing to use a medically acceptable method (as defined by the Investigator) of birth control. * Body mass index (BMI) within 19 and 29.9 kilograms per meter squared (kg/m²). * No clinically significant abnormalities (as determined by the Principal Investigator) in hematology, blood chemistry and urinalysis lab tests at screening. * No history of alcohol or drug abuse within the past year. Negative urinary drugs of abuse and alcohol screen determined within 21 days of the start of the study and at check-in Day -1. * Must be able to understand the requirements of the study and must be willing to comply with the requirements of the study.
Exclusion criteria
* Any medical condition or clinical laboratory test which in the judgment of the Investigator makes the participant unsuitable for the study. * Pregnant or breast-feeding women. * Use of any prescription within 14 days prior to dosing (except hormonal contraceptives) or over the-counter medications, including vitamins and herbal or dietary supplements within 7 days prior to dosing unless approved by the Investigator and Medical Monitor. * History within the previous 3 years or current evidence of abuse of any drug, prescription or illicit, or alcohol; a positive urine screen for drugs of abuse or alcohol. * History of orthostatic hypotension with or without syncope. * At imminent risk of suicide (positive response to question 4 or 5 on the Columbia-Suicide Severity Rating Scale \[C-SSRS\]) or had a suicide attempt within 6 months prior to screening. * Participation in any clinical trial of an experimental drug or device in the previous 30 days. * Positive Hepatitis C antibody, Hepatitis B surface antigen, or positive human immunodeficiency virus (HIV) antibody. * Donated plasma in the 7 days or blood in the 3 months preceding study drug administration. * Inability to communicate well with the Investigator and study staff (i.e., language problem, poor mental development or impaired cerebral function). * Inability to fast or consume the food provided in the study. * Relatives of, or staff directly reporting to, the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics - Cmax (ng/mL) | Sequential timepoints on each dosing day pre-dose to 30 h (timepoints - pre-dose and then 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours post dose) | This study was designed to estimate the relative bioavailability of lasmiditan 200 mg in the fed state relative to the fasted state. For each primary pharmacokinetic endpoint, i.e., Area under concentration curve (time zero to last, time zero to infinity), Maximum concentration, point estimates and corresponding 90% confidence intervals were constructed. Duration of the study was approximately 5 weeks, including up to 3 weeks for screening and 16 days on study (2 - 3 day dosing periods, 6 day washout period and follow-up). |
| Pharmacokinetics - Tmax (Hours) | Sequential timepoints on each dosing day pre-dose to 30 h (timepoints - pre-dose and then 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours post dose) | This study was designed to estimate the relative bioavailability of lasmiditan 200 mg in the fed state relative to the fasted state. For each primary pharmacokinetic endpoint, i.e., Area under concentration curve (time zero to last, time zero to infinity), Maximum concentration, point estimates and corresponding 90% confidence intervals were constructed. Duration of the study was approximately 5 weeks, including up to 3 weeks for screening and 16 days on study (2 - 3 day dosing periods, 6 day washout period and follow-up). |
| Pharmacokinetics - AUC0-t (ng.h/mL) | Sequential timepoints on each dosing day pre-dose to 30 h (timepoints - pre-dose and then 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours post dose) | This study was designed to estimate the relative bioavailability of lasmiditan 200 mg in the fed state relative to the fasted state. For each primary pharmacokinetic endpoint, i.e., Area under concentration curve (time zero to last, time zero to infinity), Maximum concentration, point estimates and corresponding 90% confidence intervals were constructed. Duration of the study was approximately 5 weeks, including up to 3 weeks for screening and 16 days on study (2 - 3 day dosing periods, 6 day washout period and follow-up). |
| Pharmacokinetics - AUC0-inf (ng.h/mL) | Sequential timepoints on each dosing day pre-dose to 30 h (timepoints - pre-dose and then 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours post dose) | This study was designed to estimate the relative bioavailability of lasmiditan 200 mg in the fed state relative to the fasted state. For each primary pharmacokinetic endpoint, i.e., Area under concentration curve (time zero to last, time zero to infinity), Maximum concentration, point estimates and corresponding 90% confidence intervals were constructed. Duration of the study was approximately 5 weeks, including up to 3 weeks for screening and 16 days on study (2 - 3 day dosing periods, 6 day washout period and follow-up). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety. Safety Measurements Include Physical Exams, Vital Signs, ECGs, Clinical Laboratory Assessments, AEs, Columbia Suicide Severity Rating Scale (C-SSRS). | Duration of study- From Screening (signing informed consent form) to End-of-Study ~ 15 days | Safety was evaluated in all participants (n=30) under the fasted condition and the fed condition, not by sequence of assigned cross-over (fed/fasted or fasted/fed). The number of unique subjects with an AE and the number of events are provided. |
| Tolerability | 15 days | Tolerability was defined as the number of participants that did not withdraw from the study early due to adverse events. |
Participant flow
Recruitment details
Fifty one (51) healthy participants were recruited according to the procedures of the Phase 1 unit. Thirty four were determined to be eligible. Thirty participants entered and completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Group A Dosing Sequence: Administration of lasmiditan 200 mg in fed state in Dosing Period 1 followed by administration of lasmiditan 200 mg in fasted state in Dosing Period 2
Lasmiditan: 2 discrete doses separated by 6 days. | 16 |
| Group B Dosing Sequence: Administration of lasmiditan 200 mg in fasted state in Dosing Period 1 followed by administration in lasmiditan 200 mg fed state in Dosing Period 2.
Lasmiditan: 2 discrete doses separated by 6 days. | 14 |
| Total | 30 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 14 Participants | 30 Participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 30 | 23 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Pharmacokinetics - AUC0-inf (ng.h/mL)
This study was designed to estimate the relative bioavailability of lasmiditan 200 mg in the fed state relative to the fasted state. For each primary pharmacokinetic endpoint, i.e., Area under concentration curve (time zero to last, time zero to infinity), Maximum concentration, point estimates and corresponding 90% confidence intervals were constructed. Duration of the study was approximately 5 weeks, including up to 3 weeks for screening and 16 days on study (2 - 3 day dosing periods, 6 day washout period and follow-up).
Time frame: Sequential timepoints on each dosing day pre-dose to 30 h (timepoints - pre-dose and then 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours post dose)
Population: all participants with evaluable PK data according to the following criteria:~* completion of both treatment regimens,~* availability of measurements of the primary PK variable(s) for both treatments (Cmax and AUC0-inf or AUC0-t),~* absence of any important protocol deviation that would have rendered the data incomparable between treatments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fed Condition | Pharmacokinetics - AUC0-inf (ng.h/mL) | 2265 ng.h/mL | Standard Deviation 938.1 |
| Fasted Condition | Pharmacokinetics - AUC0-inf (ng.h/mL) | 1906 ng.h/mL | Standard Deviation 751.4 |
Primary
Pharmacokinetics - AUC0-t (ng.h/mL)
This study was designed to estimate the relative bioavailability of lasmiditan 200 mg in the fed state relative to the fasted state. For each primary pharmacokinetic endpoint, i.e., Area under concentration curve (time zero to last, time zero to infinity), Maximum concentration, point estimates and corresponding 90% confidence intervals were constructed. Duration of the study was approximately 5 weeks, including up to 3 weeks for screening and 16 days on study (2 - 3 day dosing periods, 6 day washout period and follow-up).
Time frame: Sequential timepoints on each dosing day pre-dose to 30 h (timepoints - pre-dose and then 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours post dose)
Population: all participantss with evaluable PK data according to the following criteria:~* completion of both treatment regimens,~* availability of measurements of the primary PK variable(s) for both treatments (Cmax and AUC0-inf or AUC0-t),~* absence of any important protocol deviation that would have rendered the data incomparable between treatments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fed Condition | Pharmacokinetics - AUC0-t (ng.h/mL) | 2244 ng.h/mL | Standard Deviation 926.2 |
| Fasted Condition | Pharmacokinetics - AUC0-t (ng.h/mL) | 1892 ng.h/mL | Standard Deviation 746 |
Primary
Pharmacokinetics - Cmax (ng/mL)
This study was designed to estimate the relative bioavailability of lasmiditan 200 mg in the fed state relative to the fasted state. For each primary pharmacokinetic endpoint, i.e., Area under concentration curve (time zero to last, time zero to infinity), Maximum concentration, point estimates and corresponding 90% confidence intervals were constructed. Duration of the study was approximately 5 weeks, including up to 3 weeks for screening and 16 days on study (2 - 3 day dosing periods, 6 day washout period and follow-up).
Time frame: Sequential timepoints on each dosing day pre-dose to 30 h (timepoints - pre-dose and then 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours post dose)
Population: all participants with evaluable PK data according to the following criteria:~* completion of both treatment regimens,~* availability of measurements of the primary PK variable(s) for both treatments (Cmax and AUC0-inf or AUC0-t),~* absence of any important protocol deviation that would have rendered the data incomparable between treatments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fed Condition | Pharmacokinetics - Cmax (ng/mL) | 394.7 ng/mL | Standard Deviation 168.7 |
| Fasted Condition | Pharmacokinetics - Cmax (ng/mL) | 322.8 ng/mL | Standard Deviation 122 |
Primary
Pharmacokinetics - Tmax (Hours)
This study was designed to estimate the relative bioavailability of lasmiditan 200 mg in the fed state relative to the fasted state. For each primary pharmacokinetic endpoint, i.e., Area under concentration curve (time zero to last, time zero to infinity), Maximum concentration, point estimates and corresponding 90% confidence intervals were constructed. Duration of the study was approximately 5 weeks, including up to 3 weeks for screening and 16 days on study (2 - 3 day dosing periods, 6 day washout period and follow-up).
Time frame: Sequential timepoints on each dosing day pre-dose to 30 h (timepoints - pre-dose and then 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours post dose)
Population: all participants with evaluable PK data according to the following criteria:~* completion of both treatment regimens,~* availability of measurements of the primary PK variable(s) for both treatments (Cmax and AUC0-inf or AUC0-t),~* absence of any important protocol deviation that would have rendered the data incomparable between treatments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fed Condition | Pharmacokinetics - Tmax (Hours) | 2.5 hours | Standard Deviation 1 |
| Fasted Condition | Pharmacokinetics - Tmax (Hours) | 1.5 hours | Standard Deviation 1 |
Secondary
Safety. Safety Measurements Include Physical Exams, Vital Signs, ECGs, Clinical Laboratory Assessments, AEs, Columbia Suicide Severity Rating Scale (C-SSRS).
Safety was evaluated in all participants (n=30) under the fasted condition and the fed condition, not by sequence of assigned cross-over (fed/fasted or fasted/fed). The number of unique subjects with an AE and the number of events are provided.
Time frame: Duration of study- From Screening (signing informed consent form) to End-of-Study ~ 15 days
Population: All the participants included in the study who received at least one dose of lasmiditan (n=30). Adverse events were considered in all participants under the fed condition and then in all participants under the fasted condition not per sequence of dosing (fed/fasted or fasted/fed).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fed Condition | Safety. Safety Measurements Include Physical Exams, Vital Signs, ECGs, Clinical Laboratory Assessments, AEs, Columbia Suicide Severity Rating Scale (C-SSRS). | 19 participants with adverse events |
| Fasted Condition | Safety. Safety Measurements Include Physical Exams, Vital Signs, ECGs, Clinical Laboratory Assessments, AEs, Columbia Suicide Severity Rating Scale (C-SSRS). | 23 participants with adverse events |
Secondary
Tolerability
Tolerability was defined as the number of participants that did not withdraw from the study early due to adverse events.
Time frame: 15 days
Population: All the participants included in the study who received at least one dose of lasmiditan (n=30). Participant disposition was considered for all participants under the fed condition and then all participants under the fasted condition not per sequence of dosing (fed/fasted or fasted/fed).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fed Condition | Tolerability | early withdrawals | 0 participants |
| Fed Condition | Tolerability | completers | 30 participants |
| Fasted Condition | Tolerability | early withdrawals | 0 participants |
| Fasted Condition | Tolerability | completers | 30 participants |