Study to Evaluate the Pharmacokinetics of Selonsertib in Participants With Normal and Impaired Hepatic Function
Condition: Diabetic Kidney Disease
MeSH terms: Kidney Diseases; Diabetic Nephropathies
Intervention: Selonsertib
Intervention description: 6 mg tablets administered orally in fed state
Intervention MeSH terms: Selonsertib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The primary objective of this study is to evaluate the pharmacokinetics (PK) of selonsertib
      in participants with impaired hepatic function relative to matched, healthy controls.
    

Eligibility criteria:

        Key Inclusion Criteria:

        All participants:

          -  Body mass index (BMI) from 18 to 40 kg/m^2, inclusive at study screening

          -  Creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault method) based on
             serum creatinine and actual body weight as measured at screening

        Participants with impaired hepatic function:

          -  Aside from hepatic insufficiency, participants must be sufficiently healthy for study
             participation based upon screening evaluations.

          -  Must have diagnosis of chronic (> 6 months), stable hepatic impairment with no
             clinically significant change in hepatic status within the 3 months (90 days) prior to
             study drug administration (Day 1).

          -  Participants with severe hepatic impairment must have a score on the
             Child-Pugh-Turcotte scale of 10-15 at screening.

          -  Participants with moderate hepatic impairment must have a score on the
             Child-Pugh-Turcotte scale of 7-9 at screening.

          -  Participants with mild hepatic impairment must have a score on the Child-Pugh-Turcotte
             scale of 5-6 at screening.

        Healthy participants (matched control):

          -  Must be in good health based upon screening evaluations.

        Key Exclusion Criteria:

        All participants:

          -  Pregnant or lactating females

          -  Have received any investigational compound or device within 30 days prior to study
             dosing

          -  Current alcohol or substance abuse

          -  A positive test result for human immunodeficiency virus (HIV-1/2) antibody

          -  Have poor venous access that limits phlebotomy

          -  Have been treated with systemic steroids, anti-HIV agents, immunosuppressant
             therapies, or chemotherapeutic agents within 3 months prior to screening or expected
             to receive these agents during the study (eg, corticosteroids, immunoglobulins, and
             other immune- or cytokine-based therapies) that would be contraindicated for other
             exclusion criteria.

          -  Significant serious skin disease, such as but not limited to rash, food allergy,
             eczema, psoriasis, or urticaria

          -  Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)

          -  Unstable cardiac disease, including history of myocardial infarction within 1 year of
             screening, recurrent episodes of ventricular tachycardia despite appropriate medical
             therapy, decompensated congestive heart failure, or dilated cardiomyopathy with left
             ventricular ejection fraction < 40%, or a family history of Long QT Syndrome, or
             unexplained death in an otherwise healthy participants between the ages of 1 and 30
             years.

          -  Syncope, palpitations, or unexplained dizziness

          -  Implanted defibrillator or pacemaker

          -  Severe peptic ulcer disease, severe gastroesophageal reflux disease, or other severe
             gastric acid hypersecretory conditions

          -  Medical or surgical treatment that permanently alters gastric absorption (eg, gastric
             or intestinal surgery). A history of cholecystectomy is not exclusionary.

          -  History of prior allogeneic bone marrow progenitor cell or solid organ
             transplantation.

          -  Currently registered on an organ transplantation list.

          -  History of bleeding from esophageal varices within 90 days prior to Admission (Day
             -1).

          -  Use of strong cytochrome P3A4 (CYP3A4) inhibitors (eg, indinavir, nelfinavir,
             ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir,
             suboxone, telithromycin, atazanavir) and strong CYP3A4 inducers (eg, carbamazepine,
             rifampin, phenytoin and St. John's wort), within 28 days prior to study drug
             administration (Day 1).

          -  Consumption of grapefruit juice, grapefruits, and Seville orange juice within 2 weeks
             prior to study drug administration (Day 1).

          -  Recent significant changes in the use of nicotine or nicotine containing products

        Participants with impaired hepatic function:

          -  Aside from hepatic insufficiency, serious or active medical or psychiatric illness
             that, in the opinion of the investigator, would interfere with treatment, assessment,
             or compliance with the protocol.

          -  Chronic hepatitis B virus (HBV) infection, defined as a positive test for hepatitis B
             surface antigen (HBsAg), unless the participant has been treated with a nucleos(t)ide
             analog (eg, tenofovir or entecavir) for at least 6 months and the HBV deoxyribonucleic
             acid (DNA) by polymerase chain reaction (PCR) assay has been persistently undetectable
             for at least 6 months.

          -  Positive test for drugs of abuse, including alcohol at screening or on Day
             -1/check-in, with the exception of opioids and tetrahydrocannabinol (THC, marijuana)
             under prescription and investigator verification for pain management. Participants who
             screen positive for benzodiazepines may be allowed if prescribed under the care of a
             physician and after review by investigator and Sponsor.

          -  Requires paracentesis > 1 time per month.

          -  Participants with hepatic impairment with co-morbid diseases not associated with
             hepatic impairment requiring medication(s) must be taking the medication(s) without a
             change in dose for > 3 months prior to screening.

          -  Changes in concomitant medications or dosage used to treat symptoms of hepatic
             impairment or associated co-morbid conditions that could lead to clinically
             significant changes in medical conditions during the course of the study that would
             affect the ability to interpret potential drug-drug interactions within 28 days prior
             to dosing.

        Healthy participants (matched control):

          -  A positive test result for hepatitis C virus (HCV) antibody, hepatitis B surface
             antigen (HBsAg), or hepatitis B core antibody (anti-HBc)

          -  Positive test for drugs of abuse, including alcohol at screening or on Day
             -1/check-in.

          -  Have any serious or active medical or psychiatric illness (including depression)
             which, in the opinion of the investigator, would interfere with treatment, assessment,
             or compliance with the protocol.

          -  History of liver disease.

          -  Have taken any prescription medications or over-the-counter medications including
             herbal products within 28 days of commencing study drug dosing with the exception of
             vitamins, acetaminophen, ibuprofen, and hormonal contraceptive medications.

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.