Clinical trial NCT03465436: A Study of Lasmiditan on the Heart in Healthy Participants
Official title: A Randomized, Double-blind, Placebo-controlled, 4-way Crossover Study to Compare the Effects on the Cardiac De- and Repolarization Duration as Well as Other Cardiac Safety Parameters of Two Doses of Oral Lasmiditan (100 mg and 400 mg) With Those of Moxifloxacin (400 mg) and Placebo in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: CoLucid Pharmaceuticals
First posted: 2018-03-14
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Time Matched Baseline in Mean Fridericia-Corrected QT (QTcF) Values of Lasmiditan and Moxifloxacin
timeFrame: Day 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
Secondary outcomes:
measure: Change From Time Matched Baseline in Mean Individually-Corrected QT (QTcI) Values of Lasmiditan and Moxifloxacin
timeFrame: Day 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
measure: Change From Baseline in Mean Cardiac Intervals: RR Interval of Lasmiditan and Moxifloxacin
timeFrame: Day 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
measure: Change From Baseline in Mean Cardiac Intervals:QRS of Lasmiditan and Moxifloxacin
timeFrame: Day 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
measure: Change From Baseline in Mean Heart Rate (HR) of Lasmiditan and Moxifloxacin
timeFrame: Day 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
measure: Number of Incidents in Electrocardiogram (ECG) Abnormalities in QTcF Interval Greater Than 450 Milliseconds
timeFrame: Day 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
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Lasmiditan
timeFrame: Day 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
measure: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC-t) of Lasmiditan
timeFrame: Day 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
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: 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.
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: