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A Study of Lasmiditan on the Heart in Healthy Participants

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT03465436
Lead Sponsor
Eli Lilly and Company
Brief Summary

The purpose of this study was to determine how two doses of lasmiditan affected the heart in healthy participants. The study also evaluated how much lasmiditan got into the blood stream and how long it took the body to get rid of it. Information about side effects was collected. The study lasted a maximum of 46 days for each participant, not including screening.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
56
Inclusion Criteria
  • Body mass index within 18.5 and 29.9 kilograms per meter squared (kg/m²)

  • In good physical and mental health as determined by the following:

    • Complete medical history
    • Complete physical examination
    • Vital signs including blood pressure (supine and standing), heart rate (supine and standing), respiratory rate, and temperature
    • Standard 12-lead ECG (triplicate ECG), followed by a 24-hour Holter ECG for arrhythmia monitoring
    • Clinical laboratory tests
Exclusion Criteria
  • Any of the following cardiac abnormalities on safety screening ECG:

    • QTcF interval >430 milliseconds (ms) for males, >450 ms for females
    • Unusual T wave morphology or flattened low voltage T waves
    • PR interval >240 ms or <110 ms
    • Second-degree or third-degree atrioventricular block
    • ECG evidence of complete left or right bundle branch block
    • Intraventricular conduction delay or QRS duration >110 ms
    • Supine resting heart rate <45 beats per minute (bpm) or >90 bpm
    • Pathological Q-waves
    • Evidence of ventricular pre-excitation
  • Participants with a history of syncope, cardiac arrest, cardiac arrhythmia or torsade de pointes, or structural heart disease

  • Participants with a family history of Long QT syndrome

  • History of allergic hypersensitivity to lasmiditan or any component of the formulations

  • History or current evidence of abuse of any drug substance, licit or illicit, including alcohol; a positive urine screen for drugs of abuse

  • Participants with a history of postural hypotension or fainting

  • Participant is not able to understand and comply with study requirements, instructions and study restrictions

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo for lasmiditan and placebo for moxifloxacin administered on Day 1 in one of four treatment periods.
MoxifloxacinMoxifloxacinA single, PO dose of moxifloxacin administered on Day 1 in one of four treatment periods.
100 milligrams (mg) LasmiditanLasmiditanA single, PO dose of 100 mg lasmiditan administered on Day 1 in one of four treatment periods.
400 mg LasmiditanLasmiditanA single, PO dose of 400 mg lasmiditan administered on Day 1 in one of four treatment periods.
Primary Outcome Measures
NameTimeMethod
Change From Time Matched Baseline in Mean Fridericia-Corrected QT (QTcF) Values of Lasmiditan and MoxifloxacinDay 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTcF = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and R-R wave (RR), which is the interval between two R waves. PR is the interval between the P wave and the ventricular depolarization wave (QRS) complex.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Mean Heart Rate (HR) of Lasmiditan and MoxifloxacinDay 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose

Heart rate was determined during ambulatory blood pressure monitoring (ABPM).

Number of Incidents in Electrocardiogram (ECG) Abnormalities in QTcF Interval Greater Than 450 MillisecondsDay 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose

ECGs were assessed for morphology abnormalities or changes in QTcf interval greater than 450 milliseconds by a board-certified cardiologist

Change From Baseline in Mean Cardiac Intervals:QRS of Lasmiditan and MoxifloxacinDay 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose

ECGs were used to calculate cardiac intervals. The QRS interval is the time the segment of the ECG that corresponds to depolarization of the ventricles.

Pharmacokinetics (PK): Maximum Concentration (Cmax) of LasmiditanDay 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan.

Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC-t) of LasmiditanDay 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose

Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC-t) of Lasmiditan.

Change From Time Matched Baseline in Mean Individually-Corrected QT (QTcI) Values of Lasmiditan and MoxifloxacinDay 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose

The corrected QT interval, individualized (QTcI) is a measurement of the electrical impulses through the largest part of the heart muscle individualized for participant pre-dose values. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.

Change From Baseline in Mean Cardiac Intervals: RR Interval of Lasmiditan and MoxifloxacinDay 1: Predose, 30 minutes postdose, 1 hour (hr), 1.5 hr, 2 hr, 2.5 hr, 3 hr, 3.5 hr, 4 hr, 6 hr, 8, hr, 12 hr and 24 hr postdose

ECGs were used to calculate cardiac intervals. The RR interval is the time between two R waves.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.

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Berlin, Germany

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