Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
Condition: Long QT Syndrome
MeSH terms: Long QT Syndrome
Intervention: Eleclazine
Intervention description: Eleclazine tablets administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hepatic Impairment

Summary:

      The primary objective of this study is to evaluate the pharmacokinetic (PK) profile of oral
      eleclazine and its metabolite, GS-623134, in participants with normal and impaired hepatic
      function. Participants in the healthy control group will be matched to participants with
      impaired hepatic function by age (± 5 years), gender, and body mass index (± 10%).
    

Eligibility criteria:

        Inclusion Criteria:

        All participants:

          -  Be a nonsmoker or consume < 20 cigarettes per day

          -  Have a calculated body mass index (BMI) from 18 to 36 kg/m^2, inclusive, at study
             screening

          -  Have a creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault method)
             based on serum creatinine and actual body weight as measured at screening

          -  Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that
             are considered clinically insignificant by the investigator

          -  Screening labs within defined thresholds

        Participants with mild, moderate, or severe hepatic impairment must also meet the following
        additional inclusion criteria:

          -  Must have diagnosis of chronic (> 6 months), stable hepatic impairment with no
             clinically significant changes within 3 months (90 days) prior to study drug
             administration (Day 1)

          -  Individuals with severe hepatic impairment must have a score on the
             Child-Pugh-Turcotte scale of 10-15 at screening. If an individual's score changes
             during the course of the study, the score at screening will be used for
             classification.

          -  Individuals with moderate hepatic impairment must have a score on the
             Child-Pugh-Turcotte scale of 7-9 at screening. If an individual's score changes during
             the course of the study, the score at Screening will be used for classification.

          -  Individuals with mild hepatic impairment must have a score on the Child-Pugh-Turcotte
             scale of 5-6 at screening. If an individual's score changes during the course of the
             study, the score at screening will be used for classification.

        Exclusion Criteria:

          -  Pregnant or lactating females

          -  History of meningitis or encephalitis, epilepsy, seizures, migraines, tremors,
             myoclonic jerks, narcolepsy, obstructive sleep apnea, anxiety, syncope, head injuries
             or a family history of seizures

          -  Presence or history of cardiovascular disease (including history of myocardial
             infarction based on ECG and/or clinical history, any history of ventricular
             tachycardia, congestive heart failure, cardiomyopathy, or left ventricular ejection
             fraction < 40%), cardiac conduction abnormalities, a family history of Long QT
             Syndrome, or unexplained death in an otherwise healthy individual between the ages of
             1 and 30 years

          -  Syncope, palpitations, or unexplained dizziness

          -  Implanted defibrillator or pacemaker

          -  Are unable to comply with study requirements or are otherwise believed, by the study
             investigator, to be inappropriate for study participation for any reason

        Participants with mild, moderate, or severe hepatic impairment must also meet the following
        additional exclusion criteria:

          -  Active hepatitis B virus (HBV) infection. Individuals who have HBsAg are ineligible

          -  Requires paracentesis > 1 time per month

          -  Severe (grade 3 or 4) encephalopathy as judged by the investigator

          -  History of gastric or esophageal variceal bleeding within the past 6 months and for
             which varices have not been adequately treated with medication and/or surgical
             procedures