Pharmacokinetic Single Dose Study of Oral Lasmiditan in Participants With Normal and Impaired Hepatic Function

NCT03040479 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: 16881CUD-P9-453H8H-CD-LAHFCOL MIG-114
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 3

Brief Summary

This is a multicenter, open-label, non-randomized, parallel-group, single dose study. This study will enroll up to 24 participants and will include 2 hepatic impaired participant groups and one group of control participants with normal hepatic function.

Conditions

Migraine

Outcome Measures

Primary Outcomes (6)

• Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)

  Maximum observed plasma concentration.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose

• Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)

  Time of maximum observed plasma concentration; if it occurs at more than one time point, Tmax is defined as the first time point with this value.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose

• Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast])

  Cumulative area under the plasma concentration time curve calculated from 0 to TLQC using the linear trapezoidal method, where TLQC represents time of last observed quantifiable plasma concentration.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose

• Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-inf])

  Area under the plasma concentration time curve extrapolated to infinity, calculated as AUC(0-tlast) + CLQC/λZ, where CLQC is the measured concentration at time TLQC Apparent elimination rate constant and λz is the estimated by linear regression of the terminal linear portion of the log concentration versus time curve.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose

• Pharmacokinetics: Apparent Elimination Rate Constant (λZ)

  Apparent elimination rate constant, estimated by linear regression of the terminal linear portion of the log concentration versus time curve.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose

• Pharmacokinetics: Terminal Elimination Half-life (T1/2)

  Terminal elimination half-life, calculated as ln(2)/λZ.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose

Secondary Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up To 35 days

Study Arms (3)

Mild hepatic impairment

EXPERIMENTAL

lasmiditan 200 mg single dose

Drug: lasmiditan 200 mg

Moderate hepatic impairment

EXPERIMENTAL

lasmiditan 200 mg single dose

Drug: lasmiditan 200 mg

Healthy participants

EXPERIMENTAL

lasmiditan 200 mg single dose

Drug: lasmiditan 200 mg

Interventions

lasmiditan 200 mg DRUG

single dose

Also known as: LY573144

Healthy participants; Mild hepatic impairment; Moderate hepatic impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants:
• Availability for the entire study period
• Motivated participant and absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; ability to cooperate adequately; ability to understand and observe the instructions of the physician or designee
• Male or female participants
• A female participant of childbearing potential - agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the drug administration, during the study and for at least 60 days after the dose.
• A male participant with sexual partners who are pregnant, possibly pregnant, or who could become pregnant must be unable to procreate, or agrees to use an accepted contraceptive regimens from first drug administration until 3 months after the drug administration.
• A male participant agrees to refrain from sperm donation from drug administration until 90 days after the drug administration
• Participant aged of at least 18 years
• Participant with a body mass index (BMI) greater than or equal to (≥1) 8.5 kilogram per square meter (kg/m²)
• Light-, non- or ex-smokers
• Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF)
• Participants with Normal Hepatic Function:
• Clinical laboratory values within the laboratory's stated normal range; if not within this range, these must be without any clinical significance
• Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, general biochemistry, endocrinology, electrocardiogram \[ECG\], and urinalysis)
• Must match by gender, as well as to the pooled mean values for age (± 10 years) and weight (± 20%) of participants with hepatic impairment

You may not qualify if:

• All Participants:
• Females who are pregnant or are lactating
• History of significant hypersensitivity to lasmiditan or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
• Participant is at imminent risk of suicide (positive response to question 4 or 5 on the Columbia- Suicide Severity Rating Scale \[C-SSRS\]) or had a suicide attempt within 6 months prior to screening
• Presence or history of any disorder (including Parkinson disease) that could interfere with completion of the study based on the opinion of the Principal Investigator
• Any history of tuberculosis and/or prophylaxis for tuberculosis
• Positive results to human immunodeficiency virus antibody/antigen (HIV Ag/Ab) Combo tests (and HIV I \& II screen at Orlando Clinical Research Center site)
• Females who are pregnant according to a positive pregnancy test
• Participants who took lasmiditan in the previous 28 days before Day 1 of this study
• Participants who took an Investigational Product (in another clinical trial) in the previous 28 days before day 1 of this study
• Participants who have already participated in this clinical study
• Donation of 500 milliliters (mL) or more of blood in the previous 56 days before day 1 of this study
• Participants with Normal Hepatic Function:
• Seated pulse rate less than or equal 50 Beats per Minute (bpm) or more than 100 bpm at screening

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Algorithme Pharma Inc: collaborator
• CoLucid Pharmaceuticals: collaborator

Study Sites (3)

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

NOCCR

Knoxville, Kentucky, 37920, United States

Location

Altasciences Company Inc./Algorithme Pharma

Mount Royal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Conditions

Migraine Disorders

Interventions

lasmiditan

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

clinicaltrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multicenter, open-label, non-randomized, parallel-group, single dose study. This study will enroll up to 24 participants and will include 2 hepatic impaired participant groups and one group of control participants with normal hepatic function.

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: February 2, 2017
• Study Start: March 14, 2017
• Primary Completion: July 17, 2017
• Study Completion: July 17, 2017
• Last Updated: November 27, 2019
• Results First Posted: November 27, 2019

Record last verified: 2018-01

Locations

US (2); CA (1)