Pharmacokinetic Single Dose Study of Oral Lasmiditan in Participants With Normal and Impaired Hepatic Function
Condition: Migraine
Intervention: lasmiditan 200 mg
Intervention description: single dose
Intervention MeSH terms: Lasmiditan
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        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