Trial Outcomes & Findings for Food-Effect Study in Healthy Participants (NCT NCT02233296)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

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)

Results posted on

2018-04-05

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	16	14
Overall Study COMPLETED	16	14
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Food-Effect Study in Healthy Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=16 Participants 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.	Group B n=14 Participants 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.	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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).

Outcome measures

Outcome measures
Measure	Fed Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.	Fasted Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.
Pharmacokinetics - Cmax (ng/mL)	394.7 ng/mL Standard Deviation 168.7	322.8 ng/mL Standard Deviation 122.0

PRIMARY outcome

Timeframe: 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

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).

Outcome measures

Outcome measures
Measure	Fed Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.	Fasted Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.
Pharmacokinetics - Tmax (Hours)	2.5 hours Standard Deviation 1.0	1.5 hours Standard Deviation 1.0

PRIMARY outcome

Timeframe: 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

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).

Outcome measures

Outcome measures
Measure	Fed Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.	Fasted Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.
Pharmacokinetics - AUC0-t (ng.h/mL)	2244 ng.h/mL Standard Deviation 926.2	1892 ng.h/mL Standard Deviation 746

PRIMARY outcome

Timeframe: 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

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).

Outcome measures

Outcome measures
Measure	Fed Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.	Fasted Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.
Pharmacokinetics - AUC0-inf (ng.h/mL)	2265 ng.h/mL Standard Deviation 938.1	1906 ng.h/mL Standard Deviation 751.4

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Fed Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.	Fasted Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.
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	23 participants with adverse events

SECONDARY outcome

Timeframe: 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).

Tolerability was defined as the number of participants that did not withdraw from the study early due to adverse events.

Outcome measures

Outcome measures
Measure	Fed Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.	Fasted Condition n=30 Participants Participants were randomized to dosing sequence of fed/fasted or fasted/fed. Data from specific condition (fed or fasted) were pooled for PK analysis.
Tolerability early withdrawals	0 participants	0 participants
Tolerability completers	30 participants	30 participants

Adverse Events

Fed Condition (n=30)

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Fasted Condition (n=30)

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fed Condition (n=30) n=30 participants at risk Participants were randomized to fed/fasted or fasted/fed. Conditions were pooled for analysis so regardless of sequence all AEs reported while participant was in fed condition are considered equally.	Fasted Condition (n=30) n=30 participants at risk Participants were randomized to fed/fasted or fasted/fed. Conditions were pooled for analysis so regardless of sequence all AEs reported while participant was in fasted condition are considered equally.
Eye disorders ALL	3.3% 1/30 • Number of events 1 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	0.00% 0/30 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.
Eye disorders vision blurred	3.3% 1/30 • Number of events 1 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	0.00% 0/30 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.
Nervous system disorders ALL	60.0% 18/30 • Number of events 24 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	76.7% 23/30 • Number of events 26 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.
Nervous system disorders Dizziness	6.7% 2/30 • Number of events 2 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	16.7% 5/30 • Number of events 5 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.
Nervous system disorders Dizziness - Postural	3.3% 1/30 • Number of events 1 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	0.00% 0/30 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.
Nervous system disorders Headache	3.3% 1/30 • Number of events 1 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	0.00% 0/30 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.
Nervous system disorders Paraesthesia	6.7% 2/30 • Number of events 2 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	3.3% 1/30 • Number of events 1 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.
Nervous system disorders Somnolence	60.0% 18/30 • Number of events 18 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	66.7% 20/30 • Number of events 20 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.
Vascular disorders ALL	6.7% 2/30 • Number of events 2 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	10.0% 3/30 • Number of events 3 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.
Vascular disorders Orthostatic hypotension	6.7% 2/30 • Number of events 2 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.	10.0% 3/30 • Number of events 3 • From signing informed consent form (ICF) to End-of-study Visit (15 days). AEs are collected from ICF until the completion of EoS/Visit 4. AEs reported prior to dosing were captured and considered non TEAEs. AEs reported more than 48 hours after dosing during the days between Dosing Period 1 and Dosing Period 2 and until the completion of EoS/Visit 4 will be captured and considered non TEAEs.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60