A Study of LY2216684 in Participants With Impaired Hepatic Function
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Intervention: LY2216684
Intervention description: Administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the effect of liver function on how much of the
      study drug (LY2216684) gets into the blood stream and how long it takes the body to get rid
      of it. Information about any side effects that may occur will also be collected.

      The duration of participation in this study is approximately 12 days, not including the
      screening visit. This study requires 1 clinic confinement of 5 days/4 nights followed by 1
      out-patient follow-up visit. A screening visit is required within 30 days prior to the start
      of the study. This research study will be an open-label study.

      The study involves a single oral dose of 18 milligrams (mg) LY2216684 given as 2 tablets.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male participants: Agree to use a reliable method of birth control during the study
             and for 3 months following the last dose of study drug.

          -  Female participants: Are women of child-bearing potential who test negative for
             pregnancy at the time of enrollment, who have used a reliable method of birth control
             for 6 weeks prior to administration of study drug, and who agree to use a reliable
             method of birth control during the study and for 1 month following the last dose of
             study drug or are women not of child-bearing potential due to surgical sterilization
             (hysterectomy, bilateral oophorectomy, or tubal ligation) or menopause (at least 1
             year without menses or 6 months without menses and follicle stimulating hormone [FSH]
             levels greater than or equal to 40 milli-internation units per milliliter [mIU/mL]).

          -  Have a body mass index (BMI) of 17.0 to 35.0 kilograms per meters squared (kg/m^2),
             inclusive, at screening.

          -  Have acceptable blood pressure and pulse rate (sitting) as determined by the
             investigator.

          -  Have venous access sufficient to allow blood sampling as per the protocol.

          -  Are reliable and willing to make themselves available for the duration of the study
             and to follow study procedures.

          -  Have given written informed consent approved by Lilly and the institutional review
             board (IRB) governing the site.

        Control Participants (Participants with Normal Hepatic Function):

          -  Are overtly healthy, as determined by medical history and physical examination.

          -  Have clinical laboratory test results within normal reference ranges for the
             investigative site or results with acceptable deviations, which are judged to be not
             clinically significant by the investigator, at the time of screening.

        Participants with Mild, Moderate, or Severe Hepatic Impairment:

          -  Participants with stable liver disease (alcoholic liver disease, post-hepatitis,
             biliary cirrhosis, cryptogenic) classified as Child-Pugh score A, B, or C (Pugh et al.
             1973).

          -  Clinical laboratory test results with deviations that are judged by the investigator
             to be compatible with the hepatic impairment of the participant or of no additional
             clinical significance for this study.

        Exclusion Criteria:

        All Participants:

          -  Are currently enrolled in, or discontinued within the last 30 days from a clinical
             trial involving an investigational drug or device or off-label use of a drug or device
             other than the study drug used in this study or are concurrently enrolled in any other
             type of medical research judged not to be scientifically or medically compatible with
             this study.

          -  Have known allergies to LY2216684 or related compounds.

          -  Are persons who have previously completed or withdrawn from this study or any other
             study investigating LY2216684 in the past 6 months from screening.

          -  Have an electrocardiogram (ECG) reading considered clinically significant by the
             investigator or a history of significant cardiac dysrhythmia or conduction defect
             that, in the opinion of the investigator, increases the risks associated with
             participating in the study.

          -  Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV
             antibodies.

          -  There is evidence or history of neurological disease such as transient ischemic
             attack, stroke, syncope episodes, encephalitis, or meningitis, except participants
             with liver disease-related encephalopathy may be allowed.

          -  Presence of acute infection with fever.

          -  Are women with a positive pregnancy test or women who are lactating.

          -  Have lost 500 milliliters (mL) or more of blood in the 3 months prior to study entry.

          -  Are participants who have an average weekly alcohol intake that exceeds 21 units per
             week, or are unwilling to adhere to restrictions during the study (1 unit = 12 ounces
             [oz] or 360 mL of beer, 5 oz or 150 mL of wine, or 1.5 oz or 45 mL of distilled
             spirits).

          -  Are participants who are unwilling to adhere to study caffeine restrictions.

          -  Are participants who are unwilling to abide by smoking restrictions while resident in
             the clinical research unit (CRU).

          -  Have a documented or suspected history of glaucoma.

        Control Participants (Participants with Normal Hepatic Function):

          -  Have significant active hematological disease, history of significant active bleeding,
             or coagulation disorder.

          -  Use or intend to use over-the-counter (including vitamins/mineral supplements, herbal
             medicine) or prescription medications 14 days, prior to enrollment and during the
             study.

          -  Have history or presence of cardiovascular, respiratory, renal, gastrointestinal,
             endocrine, hematological, or neurological disorders capable of significantly altering
             the absorption, metabolism, or elimination of drugs; of constituting a risk when
             taking the study medication; or of interfering with the interpretation of data.

          -  Regularly use known drugs of abuse and/or show positive findings on urinary drug
             screening.

          -  Evidence of hepatitis C and/or positive hepatitis C antibody.

          -  Evidence of hepatitis B and/or positive hepatitis B surface antigen.

          -  Show evidence of significant active neuropsychiatric disease.

        Participants with Mild, Moderate, or Severe Hepatic Impairment:

          -  Evidence of any significant active disease other than that responsible for or
             associated with liver impairment.

          -  Have history or presence of cardiovascular, respiratory, renal, endocrine,
             hematological, or neurological disorders capable of significantly altering the
             absorption, metabolism, or elimination of drugs or of constituting a risk when taking
             the study medication or interfering with the interpretation of data.

          -  Evidence of hepatorenal syndrome.

          -  Spontaneous bacterial peritonitis within 6 months of study entry.

          -  Variceal bleeding within 3 months of study entry.

          -  Severe hyponatremia (sodium [Na] <120 millimole per liter [mmol/L]).

          -  Presence of hepatocellular carcinoma.

          -  Severe encephalopathy.

          -  Hemoglobin <9.0 grams per deciliter (g/dL).

          -  Platelet count <50 x 10^9 cells per liter (cells/L), values <50 x 10^9 cells/L may be
             permitted at the discretion of the investigator in consultation with the sponsor.

          -  Concomitant use of any drug except those indicated for the treatment of liver disease
             or related complications.

          -  Concomitant use of anticoagulants including warfarin.

          -  Regular use of drugs of abuse and/or positive findings on urinary drug screening
             except those prescribed for related complications (such as, pain, insomnia, or
             anxiety) of liver disease.

          -  The use of medication known to interfere with hepatic metabolism (such as,
             barbiturates or phenothiazines) or known to alter other major organs or systems within
             30 days prior to study entry.