Clinical trial NCT03252015: A Study of Multiple Doses of Lasmiditan in Healthy Participants
Official title: Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Drug-Drug Interaction Study of Lasmiditan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2017-08-16
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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* Have previously completed or withdrawn from this study or any other study investigating Lasmiditan, and have previously received Lasmiditan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

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline through 14 days after last administration of study drug
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan on Day 1
timeFrame: Lasmiditan PK: Day 1:0.5 hour (hr), 1hr , 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24hr and 48 hr postdose
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan on Day 7
timeFrame: Lasmiditan PK: Day 7: 0.5hour(hr), 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24hr postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Curve to the End of the Dosing Period (AUC[Tau]) Lasmiditan on Day 1
timeFrame: Day 1:0.5 hour (hr), 1hr , 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, and 24hr postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Curve to the End of the Dosing Period (AUC[Tau]) Lasmiditan on Day 7
timeFrame: Lasmiditan PK: Day 7: 0.5hour(hr), 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr,and 24hr postdose
measure: Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) Total Score
timeFrame: PreDose Day 7 and Day 21
measure: Physician Withdrawal Checklist (PWC)Total Score
timeFrame: Day 7 and Day 21 at anytime
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Metabolite M8 on Day 1
timeFrame: Day 1: 0.5 hr, 1hr, 1.5hr, 2 hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24 hr adn 48 hr postdose
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Metabolite M8 on Day 7
timeFrame: Day 7: Predose, 0.5hr, 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24 hr and 48 hr postdose
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Midazolam
timeFrame: Day -3: Predose, 0.5 hour(hr), 1hr, 1.5hr. 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, and 12 hr postdose,
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Midazolam on Day 7
timeFrame: Day 7:Predose, 0,5hr,1hr, 1.5hr. 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, and 12 hr postdose
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Daytona Beach
state: Florida
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: