Clinical trial NCT02050815 (phase 1, status: terminated)
Conditions: hepatic impairment
ICD codes: Z73.82, G31.84, M10.38, M10.30, M10.311, M10.312, M10.319
Drugs: mek162
SMILES: CN1C=NC2=C(F)C(NC3=CC=C(Br)C=C3F)=C(C=C12)C(=O)NOCCO
Reason stopped: 
    the sponsor is terminating the study because the primary objective was achieved after 5 of the
    6 subjects were assessed in the final cohort.
  
Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent prior to any screening procedures

          -  Male or female (postmenopausal or sterilized)

          -  Subject body weight at least 45 kg and a body mass index (BMI) in the range of 18 to
             35.0 kg/m2

          -  Subjects with normal hepatic function must have total bilirubin ≤ upper limit of
             normal (≤ ULN), alanine aminotransferase (ALT), aspartate aminotransferase (AST),
             gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) ≤ ULN, serum creatinine
             ≤ ULN, serum amylase and lipase ≤ ULN

        Additional inclusion criteria for subjects with abnormal liver function determined by
        elevation of serum total bilirubin are:

          -  Absolute neutrophil count (ANC) > 1000 cell/mm3

          -  Hb > 9 mg/dl,

          -  Platelet count > 30,000/mm3

          -  Serum creatinine ≤ 1.8 mg/dl

          -  Otherwise considered healthy and free of significant medical disorders unrelated to
             the subject's hepatic disorder

        Exclusion Criteria:

          -  Women of child-bearing potential

          -  Pregnant or nursing (lactating) women

          -  Subjects with impaired cardiovascular function or clinically significant
             cardiovascular diseases

          -  Uncontrolled arterial hypertension despite medical treatment

          -  History or current evidence of retinal vein occlusion (RVO) or current risk factors of
             RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or
             hypercoagulability syndromes),

          -  History of Gilbert's syndrome

          -  Immuno-compromised subjects (including known history/seropositivity of HIV)

          -  Any surgical or medical condition (other than hepatic impairment) or receiving any
             pharmacological treatment which might significantly alter the absorption or metabolism
             of drugs or which may jeopardize the subject in case of participation in the study

          -  Antecedent of malignancy with the following exceptions: adequately treated basal cell
             or squamous cell carcinoma of the skin

          -  Subjects who have neuromuscular disorders that are associated with elevated CK (e.g.,
             inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal
             muscular atrophy)

          -  Subjects who have undergone major surgery ≤ 3 weeks prior to starting study drug or
             who have not recovered from side effects of such procedure

          -  History of clinically significant drug allergy

          -  Prior therapy with a MEK-inhibitor

          -  Use of an investigational drug within 30 days of screening

          -  Current smoker or has used tobacco products or products containing nicotine within 7
             days prior to dosing of study drug

          -  Consumption of alcohol within 3 days prior to dosing or during the study

        Additional exclusion criteria for subjects with normal hepatic function:

        - Clinical evidence of liver disease or liver injury as indicated by abnormal liver
        function tests such as ALT, AST, GGT, alkaline phosphatase, or serum bilirubin. ALT and AST
        beyond the normal range before inclusion Presence of impaired renal function as indicated
        by abnormal creatinine (creatinine clearance < 80 mL/min) values and/or serum creatinine
        ≥1.8 mg/dL- A positive Hepatitis B or Hepatitis C test result

        Additional exclusion criteria for subjects with elevation of serum bilirubin > UNL:

          -  Symptoms or history of encephalopathy (Grade II or worse) within 4 weeks of study
             entry

          -  Clinical evidence of severe ascites requiring intervention

          -  International normalized ratio (INR) >2.5

          -  Any evidence of progressive liver disease within the last 3 weeks prior to the
             screening visit) as indicated by worsening of clinical manifestations (i.e.: ascites,
             encephalopathy) and/or laboratories abnormalities (liver transaminases, alkaline
             phosphatase and GGT or a ≥ 50% worsening of serum bilirubin or prothrombin time)

          -  History of surgical portosystemic shunt with complications (i.e. hepatic
             encephalopathy, heart failure)

          -  Active bleeding during the last 28 days prior to dosing including variceal bleeding