A Study of Multiple Doses of Lasmiditan in Healthy Participants

Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Drug-Drug Interaction Study of Lasmiditan

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Lasmiditan; Drug: Probe Drug Cocktail

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Daytona Beach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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• Have previously completed or withdrawn from this study or any other study investigating Lasmiditan, and have previously received Lasmiditan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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Probe Drug Cocktail (Cohort 1a); Probe Drug Cocktail administered orally on Day -3.	Drug: Probe Drug Cocktail; Administered orally
EXPERIMENTAL: 200 milligrams (mg) Lasmiditan+Probe Drug Cocktail (Cohort 1); 200 mg lasmiditan administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.	Drug: Lasmiditan; Administered orally; Other Names: LY573144; Drug: Probe Drug Cocktail; Administered orally
PLACEBO_COMPARATOR: Placebo+Probe Drug Cocktail (Cohort 1b); Placebo administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.	Drug: Placebo; Administered orally; Drug: Probe Drug Cocktail; Administered orally
EXPERIMENTAL: 400 mg Lasmiditan (Cohort 2a); 400 mg lasmiditan administered orally for 7 days.	Drug: Lasmiditan; Administered orally; Other Names: LY573144
EXPERIMENTAL: Placebo (Cohort 2b); Placebo administered orally for 7 days.	Drug: Placebo; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	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.	Baseline through 14 days after last administration of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan on Day 1	PK: Cmax of lasmiditan	Lasmiditan PK: Day 1:0.5 hour (hr), 1hr , 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24hr and 48 hr postdose
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan on Day 7	PK: Cmax of lasmiditan Day 7	Lasmiditan PK: Day 7: 0.5hour(hr), 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24hr postdose
Pharmacokinetics (PK): Area Under the Concentration Curve to the End of the Dosing Period (AUC[Tau]) Lasmiditan on Day 1	PK: AUCtau of lasmiditan	Day 1:0.5 hour (hr), 1hr , 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, and 24hr postdose
Pharmacokinetics (PK): Area Under the Concentration Curve to the End of the Dosing Period (AUC[Tau]) Lasmiditan on Day 7	PK AUCtau of lasmiditan	Lasmiditan PK: Day 7: 0.5hour(hr), 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr,and 24hr postdose
Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) Total Score	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.	PreDose Day 7 and Day 21
Physician Withdrawal Checklist (PWC)Total Score	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.	Day 7 and Day 21 at anytime
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Metabolite M8 on Day 1	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.	Day 1: 0.5 hr, 1hr, 1.5hr, 2 hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24 hr adn 48 hr postdose
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Metabolite M8 on Day 7	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.	Day 7: Predose, 0.5hr, 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24 hr and 48 hr postdose
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Midazolam	PK: Cmax of midazolam.	Day -3: Predose, 0.5 hour(hr), 1hr, 1.5hr. 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, and 12 hr postdose,
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Midazolam on Day 7	PK of midazolam.	Day 7:Predose, 0,5hr,1hr, 1.5hr. 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, and 12 hr postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 15, 2017
• Primary Completion (ACTUAL): January 2, 2018
• Study Completion (ACTUAL): January 2, 2018

Study Registration Dates

• First Submitted: August 15, 2017
• First Submitted That Met QC Criteria: August 15, 2017
• First Posted (ACTUAL): August 16, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 10, 2020
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin Receptor Agonists; Lasmiditan
• Other Study ID Numbers: 16859; H8H-MC-LAHE (OTHER: Eli Lilly and Company)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No