A Study of Lasmiditan and Propranolol in Healthy Participants

Effect of Lasmiditan on Heart Rate and Blood Pressure in Healthy Subjects Receiving Oral Doses of Propranolol

This study will assess the effects on heart rate and blood pressure when a single dose of lasmiditan is administered with a daily dose of propranolol. This study will also measure how much lasmiditan gets into the bloodstream after taking lasmiditan alone and after taking it together with propranolol. The study will also look at how well both drugs are tolerated. Information about any side effects that may occur will be collected.

This study will last approximately 45 days including screening. This study will require 13 days/12 nights in a Clinical Research Unit (CRU) followed by 1 follow-up appointment approximately 7 days after the last dose. 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: Lasmiditan; Drug: Propranolol

• Study Type: Interventional
• Enrollment (Actual): 44
• 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 to 35 kilograms per meter squared (kg/m²) inclusive, at the time of screening

Exclusion Criteria:

• Have known allergies to lasmiditan, propranolol, related compounds or any components of the formulation of lasmiditan or propranolol
• Have a history of, or electrocardiogram (ECG) findings of, clinically significant bradycardia, heart block, tachy or brady arrhythmias, sick sinus syndrome/sinoatrial block, or second or third-degree heart block, or have any other abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study
• Have an abnormal supine blood pressure, defined as systolic blood pressure less than (<) 95 or greater than (>) 140 millimeters of mercury (mmHg) or diastolic blood pressure <65 or >90 mmHg at screening
• Have a supine pulse rate of <50 or >90 beats per minute (bpm) at screening
• Have an estimated glomerular filtration rate (eGFR) of <60 milliliter per minute (mL/min) per 1.73 meter squared (m2)
• Show evidence of significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, depression)
• Show a history of central nervous system (CNS) conditions such as strokes, transient ischaemic attacks, significant head trauma, CNS infections, migraines, brain surgery or any other neurological conditions that, in the opinion of the investigator, increases the risk of participating in the study
• Are women with a positive pregnancy test or women who are lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lasmiditan Reference; Single oral dose of lasmiditan 200 mg on Day 1 as reference treatment.	Drug: Lasmiditan; Administered orally; Other Names: LY573144
ACTIVE_COMPARATOR: Propranolol Reference; Twice-daily oral doses of propranolol 80 mg on Days 4-10 as reference treatment.	Drug: Propranolol; Administered orally
EXPERIMENTAL: Lasmiditan + Propranolol Test; Single oral dose of lasmiditan 200 mg + two oral doses of propranolol 80 mg on Day 9 as test treatment.	Drug: Lasmiditan; Administered orally; Other Names: LY573144; Drug: Propranolol; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan	Change from baseline in mean hourly heart rate recorded as beats per minute and collected by Holter ambulatory monitoring in response to propranolol administered alone and in combination with lasmiditan.	Baseline (Day 8), Day 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol	Maximum concentration of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan	Maximum concentration of propranolol when administered alone on Day 8 and when coadministered with lasmiditan on Day 9.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol	AUC versus time curve (AUC 0-tlast) of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan	AUC versus time curve of propranolol during one dosing interval when administered alone on Day 8 and when administered with lasmiditan on Day 9.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan	Change from baseline in PR interval, the interval between the P wave and the QRS complex calculated from electrocardiogram (ECG) data.	Baseline (Day 8), Day 9
Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan	Change from baseline in systolic blood pressure was measured in supine position.	Baseline (Day 8), Day 9
Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan	Change from baseline in diastolic blood pressure was measured in supine position.	Baseline (Day 8), Day 9

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 31, 2017
• Primary Completion (ACTUAL): November 22, 2017
• Study Completion (ACTUAL): November 22, 2017

Study Registration Dates

• First Submitted: August 31, 2017
• First Submitted That Met QC Criteria: August 31, 2017
• First Posted (ACTUAL): September 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 16, 2019
• Last Update Submitted That Met QC Criteria: December 2, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Serotonin Agents; Serotonin Receptor Agonists; Propranolol; Lasmiditan
• Other Study ID Numbers: 16857; H8H-MC-LAHD (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