A Study of Multiple Doses of Lasmiditan in Healthy Participants

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Probe Drug Cocktail
Drug: Placebo
Drug: Lasmiditan

Registration Number: NCT03252015

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this study is to look at how much lasmiditan, study drug, gets into the blood stream and how long it takes the body to get rid of it.

When drugs are taken together, one or all of the drugs used in combination may be affected. This study will also evaluate the concentrations in the blood of a probe drug cocktail taken alone and in combination with lasmiditan. Information about any side effects that may occur will also be collected.

The study has two parts. Participants will only enroll in one part. This study will last about 25 days for group 1 and 22 days for group 2, not including screening. Screening is required within 28 days prior to the start of the study.

This study is for research purposes only and is not intended to treat any medical condition.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 70

Inclusion Criteria

Healthy males or females, as determined by 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 participated, within the last 30 days, in a clinical study involving an Investigational Product (IP)
Have previously completed or withdrawn from this study or any other study investigating Lasmiditan, and have previously received Lasmiditan
Have clinically significant abnormality in the 12-lead ECG, including corrected QT interval (QTc) with Fridericia's correction (QTcF) greater than (>) 450 milliseconds (ms) for men or >470 ms for women or any abnormality that in the opinion of the investigator increases the risk of participating in the study (not limited to significant bradycardia or heart block)
History of, show evidence of, or are undergoing treatment for significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, depression), have a recent history of a suicide attempt (30 days within screening visit and any time between screening visit and baseline); or are clinically judged by the investigator to be at risk for suicide
History of hypoglycemia
Known history of glucose-6-phosphate dehydrogenase deficiency
Are taking a concomitant medication or a dietary substance that affects cytochrome P450 (CYP)1A2, CYP2C9, and/or CYP3A isotypes within 14 days of screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo+Probe Drug Cocktail (Cohort 1b)	Probe Drug Cocktail	Placebo administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.
Probe Drug Cocktail (Cohort 1a)	Probe Drug Cocktail	Probe Drug Cocktail administered orally on Day -3.
Placebo (Cohort 2b)	Placebo	Placebo administered orally for 7 days.
200 milligrams (mg) Lasmiditan+Probe Drug Cocktail (Cohort 1)	Probe Drug Cocktail	200 mg lasmiditan administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.
Placebo+Probe Drug Cocktail (Cohort 1b)	Placebo	Placebo administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.
200 milligrams (mg) Lasmiditan+Probe Drug Cocktail (Cohort 1)	Lasmiditan	200 mg lasmiditan administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.
400 mg Lasmiditan (Cohort 2a)	Lasmiditan	400 mg lasmiditan administered orally for 7 days.

Primary Outcome Measures

Name	Time	Method
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 14 days after last administration of study drug	A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module. Adverse events for this outcome measure are reported by arm. SAEs are reported by study drug in the Adverse Events module.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan on Day 1	Lasmiditan PK: Day 1:0.5 hour (hr), 1hr , 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24hr and 48 hr postdose	PK: Cmax of lasmiditan
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan on Day 7	Lasmiditan PK: Day 7: 0.5hour(hr), 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24hr postdose	PK: Cmax of lasmiditan Day 7
Pharmacokinetics (PK): Area Under the Concentration Curve to the End of the Dosing Period (AUC[Tau]) Lasmiditan on Day 1	Day 1:0.5 hour (hr), 1hr , 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, and 24hr postdose	PK: AUCtau of lasmiditan
Pharmacokinetics (PK): Area Under the Concentration Curve to the End of the Dosing Period (AUC[Tau]) Lasmiditan on Day 7	Lasmiditan PK: Day 7: 0.5hour(hr), 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr,and 24hr postdose	PK AUCtau of lasmiditan
Physician Withdrawal Checklist (PWC)Total Score	Day 7 and Day 21 at anytime	Physician Withdrawal Checklist (PWC) : 20 item physician rated interview measuring anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception and cognition); range 0 (not present) to 3 (severe); total score range: 0 to 60; higher score = more affected.
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Metabolite M8 on Day 1	Day 1: 0.5 hr, 1hr, 1.5hr, 2 hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24 hr adn 48 hr postdose	Cmax of M8 on Day 1 following a single and repeated oral daily dosing of 200 and 400 mg lasmiditan. M8 is a metabolite of lasmiditan.
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Metabolite M8 on Day 7	Day 7: Predose, 0.5hr, 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24 hr and 48 hr postdose	Cmax of M8 on Day 7 following a single and repeated oral daily dosing of 200 and 400 mg lasmiditan. M8 is a metabolite of lasmiditan.
Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) Total Score	PreDose Day 7 and Day 21	BWSQ is a 20 item, self administered withdrawal symptom questionnaire. Each question is scored by a 0 representing no withdrawal symptoms, 1 for moderate symptoms, 2 for severe symptoms. Total score at each time point will be averaged for each treatment in each cohort.
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Midazolam on Day 7	Day 7:Predose, 0,5hr,1hr, 1.5hr. 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, and 12 hr postdose	PK of midazolam.
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Midazolam	Day -3: Predose, 0.5 hour(hr), 1hr, 1.5hr. 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, and 12 hr postdose,	PK: Cmax of midazolam.