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

November 8, 2019 updated by: Eli Lilly and Company

A Phase I, Multicenter, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral Lasmiditan in Subjects With Normal and Impaired Hepatic Function

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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. Approximately four participants with mild hepatic impairment will be enrolled first (Group 1). To ensure participant safety, following dosing of these first four participants, a safety meeting will take place to review the safety data prior to dosing additional participants. After safety and pharmacokinetic (PK) results from the first four participants have been reviewed, an additional four participants with mild hepatic impairment (remainder of Group 1) will be enrolled concurrently with the moderate hepatic impairment group (Group 2). Thereafter, matched participants with normal hepatic function (Group 3) will be enrolled. All participants will participate in one treatment period and will receive a single dose of lasmiditan in the fasting state.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Mount-Royal, Quebec, Canada, H3P 3P1
        • Altasciences Company Inc./Algorithme Pharma
  • United States
    • Florida
      • Orlando, Florida, United States, 32809
        • Orlando Clinical Research Center
    • Kentucky
      • Knoxville, Kentucky, United States, 37920
        • NOCCR

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Hepatic Impaired Participants:

  • Considered clinically stable in the opinion of the Investigator
  • Presence of mild hepatic impairment (Child-Pugh Class A: 5-6 points) or moderate hepatic impairment (Child-Pugh Class B: 7-9 points) at screening

Exclusion Criteria:

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
  • Seated blood pressure below 90/60 millimeters of mercury (mmHg) or higher than 140/90 mmHg at screening
  • Presence of significant gastrointestinal, liver, or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs or known to potentiate or predispose to undesired effects
  • History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
  • Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
  • Presence of out-of-range cardiac interval (PR < 110 milliseconds [msec], PR > 220 msec, QRS < 60 msec, QRS >119 msec and QTc > 450 msec for males and > 460 msec for females) on the screening ECG or other clinically significant ECG abnormalities
  • Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
  • Positive screening of alcohol and/or drugs of abuse
  • Positive results to Hepatitis B surface Antigen (HBsAG [B] [hepatitis B]) or Hepatitis C Virus (HCV [C]) tests
  • Any clinically significant illness in the previous 28 days before day 1 of this study
  • Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study
  • Participants who donated 50 mL or more of blood in the previous 28 days before day 1 of this study

Hepatic Impaired Participants:

  • Seated pulse rate less than 40 bpm or more than 110 bpm at screening
  • Seated blood pressure below 90/50 mmHg or higher than 170/100 mmHg at screening
  • History of hepatic transplant
  • Acute exacerbation of hepatic disease within 14 days of study drug administration
  • History or presence, in the opinion of the Investigator, of significant clinically unstable respiratory, cardiovascular, pulmonary, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
  • Have poorly controlled Type 1 or Type 2 diabetes as defined by Hemoglobin A1c >10%
  • Evidence of hepatocellular carcinoma present or acute hepatic disease from infection or drug toxicity at the time of screening
  • Presence of severe encephalopathy
  • Presence of surgically-created or transjugular intrahepatic portal systemic shunts
  • History of any major surgery within 6 months before Day 1
  • History of bariatric surgery or any other gastrointestinal surgery that may induce malabsorption
  • Estimated creatinine clearance by Cockcroft-Gault equation < 40 mL/min/1.73 m² at screening
  • Presence of clinically significant physical, laboratory, or ECG finding that, in the opinion of the Investigator and/or Sponsor, may interfere with any aspect of study conduct or interpretation of results
  • Participants with acute, unstable, or untreated significant medical conditions.
  • Positive screening of alcohol and/or drugs of abuse unless results can be explained by a prescription medication
  • Participants who donated 100 mL or more of blood in the previous 28 days before day 1 of this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Mild hepatic impairment
lasmiditan 200 mg single dose
Drug: lasmiditan 200 mg
single dose
Other Names:
  • LY573144
Experimental: Moderate hepatic impairment
lasmiditan 200 mg single dose
Drug: lasmiditan 200 mg
single dose
Other Names:
  • LY573144
Experimental: Healthy participants
lasmiditan 200 mg single dose
Drug: lasmiditan 200 mg
single dose
Other Names:
  • LY573144

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
Time Frame: 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
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 Frame: 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
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])
Time Frame: 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
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])
Time Frame: 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
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)
Time Frame: 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
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)
Time Frame: 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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up To 35 days
Safety assessed from time of consent through end of study (up to 35 days). A summary of all reported serious adverse events (SAE) and other adverse events regardless of causality are provided in the Adverse Events module of this record.
Up To 35 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Algorithme Pharma Inc
CoLucid Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 14, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 17, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 17, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 31, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2017

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 27, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 8, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16881
  • CUD-P9-453 (Other Identifier: Algorithme Pharma)
  • H8H-CD-LAHF (Other Identifier: Eli Lilly and Company)
  • COL MIG-114 (Other Identifier: CoLucid Pharmaceuticals)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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