A Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal or Moderately Impaired Hepatic Function
Condition: Healthy Study Participants; Impaired Hepatic Function
Intervention: Padsevonil
Intervention description: Padsevonil will be administered in predefined dosages.
Intervention MeSH terms: Padsevonil
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Padsevonil; Phase 1; Pharmacokinetic; PSL

Summary:

      The purpose of the study is to evaluate the plasma pharmacokinetic (PK), safety and
      tolerability of padsevonil (PSL) in hepatically impaired and non-hepatically impaired study
      participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must be male or female 18 to 70 years of age, inclusive, at the time of
             signing the informed consent

          -  Participant must have body weight of at least 50 kg (males) or 45 kg (females) and
             body mass index within the range 18 to 38 kg/m^2 (inclusive)

          -  Participants must meet the following requirements to be included in the study:

               1. A male participant must agree to use contraception during both Treatment Periods
                  and for at least 7 days after the last dose of study medication and refrain from
                  donating sperm during this period

               2. A female participant is eligible to participate if she is not pregnant, not
                  breastfeeding, and at least 1 of the following conditions applies:

                  Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the
                  contraceptive guidance during both Treatment Periods and for at least 90 days (or
                  5 terminal half-lives) after the final dose of study medication

                  Specific inclusion criteria for study participants WITH moderate hepatic
                  insufficiency:

          -  Participant must have characteristics that will meet the clinical criteria usually
             found in participants with chronic hepatic insufficiency, as determined by medical
             history and physical examinations (eg, echography, scintigraphy, biopsy, or some
             specific laboratory values as evidence)

        Exclusion Criteria:

          -  Participant has any medical or psychiatric condition that, in the opinion of the
             Investigator, could jeopardize or compromise the study participant's ability to
             participate in this study, such as a history of schizophrenia, or other psychotic
             disorder, bipolar disorder, or severe unipolar depression. The presence of potential
             psychiatric exclusion criteria will be determined based on the psychiatric history
             collected at Screening Visit

          -  Participant has a known hypersensitivity to any components of the study medication as
             stated in this protocol

          -  Participant has a lifetime history of suicide attempt (including an actual attempt,
             interrupted attempt, or aborted attempt), or has had suicidal ideation in the past 6
             months

          -  Participant has past or intended use of over-the-counter or prescription medication
             including herbal remedies and hepatic enzyme inhibitors within 2 weeks or 5 half-lives
             prior to dosing, particularly for participants with hepatic impairment where t1/2 may
             be prolonged. Specific medications may be allowed. Participant has used hepatic
             enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, phenytoin, isoniazid, or
             rifampicin, etc.) within 2 months prior to dosing unless required to treat an adverse
             event (AE). This does not include oral contraceptives not exceeding 30 μg ethinyl
             estradiol or postmenopausal hormone replacement therapy (HRT) or implants, patches, or
             intrauterine devices (IUDs) /intrauterine systems (IUSs) delivering progesterone (for
             female study participants) or acetaminophen with a maximal dose of 2 g/day or with a
             maximum of 10g over 15 days. In case of uncertainty, the UCB Study Physician should be
             consulted

          -  Participant has a history of chronic alcohol or drug abuse within the previous 12
             months. Participant has a positive pre-study drug/alcohol screen (to include at
             minimum: amphetamines, barbiturates, cocaine, opiates, cannabinoids, and
             benzodiazepines). A participant with a positive finding on the drug screen may still
             be enrolled at the discretion of the Investigator if a plausible clinical explanation
             exists (eg, prior or concomitant medication use)

          -  Participant has a history of unexplained syncope or a family history of sudden death
             due to long QT syndrome

          -  Participant has renal impairment as indicated by an estimated glomerular filtration
             rate (GFR) <60 mL/min, calculated by using the Chronic Kidney Disease Epidemiology
             Collaboration (CKD-EPI)

          -  Participant tests positive for human immunodeficiency virus-1/2 antibody (HIV-1/2Ab)
             at Screening or within 3 months prior to the first dose of study medication

        Specific exclusion criteria for study participants WITHOUT hepatic insufficiency

          -  Participant has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or
             alkaline phosphatase (ALP) >1.0x upper limit of normal (ULN)

          -  Participant has bilirubin >1.0xULN (isolated bilirubin >1.0xULN is acceptable if
             bilirubin is fractionated and direct bilirubin <35%)

          -  Participant has current or chronic history of liver disease or known hepatic or
             biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic
             gallstones) Note: For participants with a Baseline result >ULN for ALT, AST, ALP, or
             total bilirubin, a baseline diagnosis and/or the cause of any clinically meaningful
             elevation must be understood and recorded in the electronic Case Report Form (eCRF).
             If participant has >ULN ALT, AST, or ALP that does not meet the exclusion limit at
             Screening, repeat the tests, if possible, prior to dosing to ensure there is no
             further ongoing clinically relevant increase. In case of a clinically relevant
             increase, inclusion of the study participant must be discussed with the UCB Study
             Physician

        Specific exclusion criteria for study participants WITH moderate hepatic insufficiency

          -  Participant has acute liver failure of any etiology

          -  Participant has biliary cirrhosis

          -  Participant has used any drug indicated for the medical care of moderate hepatic
             insufficiency that is not established in dose and schedule for at least 14 days before
             the first liver function test (except paracetamol with a maximal dose of 2 g/day or
             with a maximum of 10 g over 15 days)