Pharmacokinetics of BAF312 in Patients With Hepatic Impairment
Condition: Hepatic Impairment
MeSH terms: Liver Diseases
Intervention: BAF312
Intervention description: Treatment with a single oral dose of 0.25 mg BAF312
Intervention MeSH terms: Siponimod
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: BAF312; Pharmacokinetics; Hepatic impairment

Summary:

      This study will investigate the pharmacokinetics of BAF312 in patients with mild, moderate
      and severe hepatic impairment compared to healthy control subjects.
    

Eligibility criteria:

        Inclusion Criteria:

        All subjects:

          -  Male and female Caucasian subjects 18 to 70 years of age

          -  At least 50 kg and body mass index (BMI) within 18-35 kg/m2.

          -  CYP2C9 wild-type (CYP2C9*1 homozygous carriers)

        Hepatic impairment:

        - Subjects must have either mild, moderate or severe hepatic impairment

        Exclusion Criteria:

        All subjects

          -  Hepatic impairment due to non-liver disease.

          -  Use of other investigational drugs within certain timelines

          -  Donation or loss of 400 mL or more of blood or plasma within eight (8) weeks prior to
             initial dosing

          -  History of cardiac rhythm abnormalities or cardiac rhythm abnormalities identified in
             the 24-h Holter ECG recording including episodes of bradycardia (HR < 50 bpm) during
             waking hours and/or arrhythmic episodes; subjects with history or presence of
             ventricular rhythm disturbances (ventricular extra-systoles >100/24h, or higher
             grade), or supraventricular arrhythmias (other than occasional supraventricular
             ectopic beats with a maximum of 5 subsequent ectopic beats per event) or subjects with
             conduction disturbances (higher than AV-block grade 1) or bradycardia or tachycardia.

          -  History of cardiac catheter ablation.

          -  Women of child-bearing potential

          -  History of malignancy of any organ system

          -  Recent and/or recurrent history of acute or chronic bronchospastic disease (including
             asthma and chronic obstructive pulmonary disease)

          -  History or presence of symptomatic postural hypotension or syncope.

          -  Total WBC or lymphocyte counts which falls outside the 1.5-fold local laboratory
             normal range or platelet count < 30,000/μL at screening or baseline.

          -  Clinically significant infection or recent vaccination with live-attenuated vaccines.

          -  History or presence of hepatitis B or C and/or positive Hepatitis B surface antigen
             (HBsAg) or Hepatitis C test result at screening.

          -  History or presence of coronary heart disease (stable or unstable), myocardial
             infarction, myocarditis, cardiomyopathy, heart failure NYHA II - IV.

        Hepatic impairment:

          -  History or presence of any non-controlled and clinically significant disease that
             could affect the study outcome or that would place the patient at undue risk.

          -  Any surgical or medical condition other than hepatic impairment which might
             significantly alter the absorption, distribution, metabolism, or excretion of drugs,
             or which may jeopardize the safety of the study subject in case of participation in
             the study.

          -  Treatment with certain drugs

        Healthy subjects:

          -  History or presence of any clinically significant disease of any major system organ
             class including (but not limited to) cardiovascular, metabolic, renal, neurological or
             psychiatric diseases.

          -  Any surgical or medical condition which might significantly alter the absorption,
             distribution, metabolism, or excretion of drugs, drugs, or which may jeopardize the
             subject in case of participation in the study.