A Study of Soticlestat in Adults With Liver Failure Compared to Those With Normal Liver Function
Condition: Hepatic Impairment; Healthy Volunteers
MeSH terms: Liver Diseases
Intervention: Soticlestat
Intervention description: Soticlestat tablets.
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug Therapy

Summary:

      The main aim is to check the effect of a single dose of soticlestat in adults with moderate
      or mild liver failure compared to healthy adults with normal liver function.

      Participants will check into the study clinic for 8 days. During the stay, one oral dose of
      soticlestat will be given and the participant will be monitored. The clinic staff will follow
      up with the participant about a week after discharge from the clinic.
    

Eligibility criteria:

        Inclusion Criteria A. For Participants with Hepatic Impairment

          1. Has a BMI greater than or equal to (>=) 18.0 and less than or equal to (<=) 40.0
             kilogram per square meter (kg/m^2), at screening. At least 50% of the participants
             will be required to be of BMI >=18.0 and <=35.0 kg/m^2, at screening.

               -  Supine blood pressure (BP) is >=80/40 millimeter of mercury (mmHg) (asymptomatic)
                  and <=150/95 mmHg at screening;

               -  Supine pulse rate (PR) is >=40 beats per minute (bpm) and <=99 bpm, at screening;

               -  QT interval corrected for heart rate using Fridericia's formula (QTcF) is <=500
                  millisecond (msec) and ECG findings considered normal or not clinically
                  significant by the Investigator or designee, at screening.

          2. Must have had chronic HI for at least 3 months before screening, and the HI must be
             stable, that is, no significant changes in hepatic function in the 30 days preceding
             screening (or since the last visit if within 6 months before screening) and treatment
             with stable doses of medication. Has a score on the Child-Pugh Class at screening as
             follows:

               -  (Arm 1) Moderate HI, Child-Pugh Class B: >=7 and <=9

               -  (Arm 2) Mild HI, Child-Pugh Class A: >=5 and <=6

          3. Should not have renal dysfunction as demonstrated by a relatively adequate renal
             function (creatinine clearance >=50 milliliter per minute [mL/min]), at screening.

        B. For Healthy Participants

          1. Has a BMI >=18.0 and <=40.0 kg/m^2, at screening. At least 50% of the participants
             will be required to be of BMI >=18.0 and <=35.0 kg/m^2, at screening. Healthy
             participants will be matched to hepatic impaired participants in this study by age
             (mean ±10 years), sex (±2 per sex), and BMI, mean ±10%.

               -  Supine BP is >=90/40 mmHg and <=150/95 mmHg, at screening;

               -  Supine PR is >=40 bpm and <=99 bpm, at screening;

               -  QTcF is <=450 msec (males) or <=470 msec (females) and ECG findings considered
                  normal or not clinically significant by the Investigator or designee, at
                  screening;

               -  Liver function tests including alanine aminotransferase (ALT), aspartate
                  aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin <= the
                  upper limit of normal (ULN) at screening and check-in.

          2. Should not have renal dysfunction as demonstrated by a relatively adequate renal
             function (creatinine clearance >=60 mL/min), at screening.

        C. For Participants with Hepatic Impairment and Healthy Participants

        1. Continuous non-smoker or moderate smoker (<=10 cigarettes/day or the equivalent) before
        screening. Participant must agree to consume no more than 5 cigarettes or equivalent/day
        from the 7 days prior check-in and until discharge from the Clinical Research Unit (CRU).

        Exclusion Criteria A. For Participants with Hepatic Impairment

          1. Has history or presence of clinically significant medical or psychiatric condition or
             disease (aside from HI) or presence of psychotic disorders such as psychosis,
             delusions, or schizophrenia in the opinion of the Investigator or designee.

          2. Has a history of liver or other solid organ transplant.

          3. Positive result at screening for human immunodeficiency virus (HIV). Hepatitis B
             surface antigen (HBsAg) positive participants are allowed to be enrolled if Hepatitis
             B virus (HBV) deoxyribonucleic acid (DNA) is below 1000 copies per milliliter (/mL) in
             the plasma. Participants with moderate or mild HI who are positive for Hepatitis C
             virus antibodies (HCVAb) can be enrolled but must not have detectable Hepatitis C
             virus (HCV) ribonucleic acid (RNA) in the plasma.

        B. For Healthy Participants

          1. Has history or presence of clinically significant medical or psychiatric condition or
             disease or presence of psychotic disorders such as psychosis, delusions, or
             schizophrenia in the opinion of the Investigator or designee.

          2. Positive results at screening for HIV, HBsAg, or HCV.

        C. For Participants with Hepatic Impairment and Healthy Participants

          1. Has been on a diet incompatible with the on-study diet, in the opinion of the
             Investigator or designee, within the 30 days prior to dosing.

          2. Any positive responses on the Columbia-Suicide Severity Rating Scale (C-SSRS) or has a
             risk of suicide according to the Investigator's judgment based on the assessment of
             the C-SSRS at screening or check-in or has made a suicide attempt in the previous 12
             months prior to dosing.