Study of Oral Lasmiditan in Participants With Normal and Impaired Renal Function
Condition: Migraine
MeSH terms: Renal Insufficiency
Intervention: Lasmiditan
Intervention description: 200 mg, single oral tablet
Intervention MeSH terms: Lasmiditan
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is a multi-center, open-label, non-randomized, parallel-group, adaptive, single dose
      study.

      This study will enroll up to 32 participants using an adaptive design that can include up to
      3 groups of 8 participants with different degree of renal impairment and one group of 8
      control participants with normal renal function.

      Screening data will be reviewed to determine participant eligibility. Participants who meet
      all inclusion criteria and none of the exclusion criteria will be entered in the study.

      First, approximately 16 participants will be enrolled with severe renal impairment and
      matched participants with normal renal function. There will be 8 participants in each of the
      following groups based on renal function at screening:

        -  Group 1: Healthy participants with normal renal function (estimated glomerular
           filtration rate [eGFR] ≥ 90 milliliters per minute per 1.73 meters squared
           [mL/min/1.73m²])

        -  Group 2: Severe renal impairment participants (eGFR < 30 mL/min/1.73m²) Based on safety
           and pharmacokinetic (PK) results from participants with severe renal impairment (Group
           2), Group 3 (Moderate Renal Impairment) and Group 4 (Mild Renal Impairment) will be
           enrolled if substantial change in the exposure of lasmiditan is observed in participants
           with severe renal impairment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 participant

          -  A female participant if of childbearing potential - must be willing to use 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 of child bearing potential must be
             willing to use accepted contraceptive regimens.

          -  A male participant agrees to refrain from sperm donation from drug administration
             until 3 months after the drug administration

          -  Participant aged of at least 18 years

          -  Participant with a body mass index (BMI) ≥18.50 kilogram per meter squared (kg/m²) and
             < 42.00 kg/m²

          -  Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes
             or less per day for at least 3 months before Day 1 of this study. An ex smoker is
             defined as someone who completely stopped smoking for at least 6 months before Day 1
             of this study

          -  Willingness to adhere to the protocol requirements as evidenced by the informed
             consent form (ICF) duly read, signed and dated by the participant

        Participants with Normal Renal 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, electrocardiogram [ECG], and
             urinalysis)

          -  For each gender, have to match by age (± 10 years) and weight (± 20%) to the pooled
             mean values of participants with severe renal impairment

          -  Have an eGFR ≥ 90 mL/min/1.73m² calculated using Modification of Diet in Renal Disease
             (MDRD) equation at screening

        Renal Impaired Participants:

          -  Considered clinically stable in the opinion of the Investigator

          -  Presence of mild renal impairment (eGFR 60-89 mL/min/1.73m²), moderate renal
             impairment (eGFR 30-59 mL/min/1.73m²), or severe renal impairment (eGFR < 30
             mL/min/1.73m²) calculated using MDRD equation 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 antigen/antibody (HIV Ag/Ab) Combo,
             Hepatitis B surface antigen (HBsAG (B) (hepatitis B) or Hepatitis C Virus (HCV [C])
             tests

          -  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)

          -  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

          -  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

          -  Participants who donated 50 mL or more of blood in the previous 28 days before Day 1
             of this study

          -  Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical
             studies, etc.) in the previous 56 days before Day 1 of this study

        Participants with Normal Renal Function:

          -  Seated pulse rate less than or equal 40 Beats per Minute (bpm) or more than - 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, including but not limited to cholecystectomy

          -  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 correct QT interval (QTc) > 450 msec for males
             and > 460 msec for females) on the screening ECG or other clinically significant ECG
             abnormalities

          -  Positive screening of alcohol and/or drugs of abuse

          -  Any clinically significant illness in the previous 28 days before Day 1 of this study

        Renal Impaired Participants:

          -  Seated pulse rate less than 50 bpm or more than 110 bpm at screening

          -  Seated blood pressure below 90/50 mmHg or higher than 180/110 mmHg at screening

          -  Currently undergoing any method of dialysis

          -  History of renal transplant

          -  History or presence, in the opinion of the Investigator, of significant clinically
             unstable respiratory, cardiovascular, pulmonary, hepatic, hematologic,
             gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric
             disease,

          -  Have poorly controlled Type 1 or Type 2 diabetes as defined by Hemoglobin A1c >10%

          -  Require immunosuppressive medications for treatment of immune-mediated renal disease
             or kidney transplant recipients

          -  Evidence of renal carcinoma present at the time of screening

          -  Have relevant clinical laboratory abnormalities, including any elevation of alanine
             aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin at screening.
             If the investigator concludes that there is no safety risk for participants with
             isolated laboratory abnormalities (eg, those that do not reflect end-organ
             dysfunction; for example, elevated bilirubin in Gilbert's participants) to participate
             in the study, such cases need to be discussed and approved by the sponsor's medical
             monitor prior to study enrollment

          -  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.
             Participants requiring treatment for renal impairment or other chronic disease (eg,
             well-controlled diabetes, hypertension) must be on a stable treatment plan (medicines,
             doses, and regimens) for at least 2 weeks (except insulin) prior to Day 1 and during
             the entire study. Small adjustments in the dosages of some concomitant medications may
             be permitted during the study, and will be discussed on a case-by-case basis. In all
             cases, the participants' treatment history must be reviewed and their enrollment must
             be agreed to by both the investigator and the sponsor's medical monitor

          -  Positive screening of alcohol and/or drugs of abuse unless results can be explained by
             a prescription medication

          -  Concurrent use of medications known to affect the elimination of serum creatinine (eg,
             trimethoprim/sulfamethoxazole [Bactrim®] or cimetidine [Tagamet®]) and competitors of
             renal tubular secretion (eg, probenecid) within 30 days prior to the first dose of
             study drug or anticipated need for these therapies through the last pharmacokinetic
             (PK) sample