Disposition of Carbon-14-Labeled LY2886721 ([^14C]-LY2886721) Following Oral Administration in Healthy Human Participants
Condition: Healthy Volunteers
Intervention: LY2886721
Intervention description: Administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Male
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Absorption; Distribution; Metabolism; Excretion

Summary:

      This open-label study is being conducted to determine the metabolism and physiological
      disposition of radiolabeled LY2886721 after a single dose in healthy male participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy males as determined by medical history and physical examination

          -  Males will be sterile (including vasectomy) or if the participant is not sterile and
             is sexually active, he will agree to use from check-in until 3 months after
             exit/discharge, 1 of the following approved methods of contraception: a male condom
             with spermicide, a sterile sexual partner, use by female sexual partner of an
             intrauterine device with spermicide, a female condom with spermicide, contraceptive
             sponge with spermicide, a diaphragm with spermicide, a cervical cap with spermicide,
             or oral, implantable, transdermal, intravaginal, or injectable contraceptives

          -  Have a body mass index of 19 to 30 kilograms per square meter (kg/m^2)

          -  Have clinical laboratory test results within normal reference range for the population
             or investigator site, or results with acceptable deviations that are judged to be not
             clinically significant by the investigator

          -  Have venous access sufficient to allow for blood sampling

          -  Have normal blood pressure and heart rate (sitting)

          -  Experience a minimum of at least 1 bowel movement per day

          -  Are reliable and willing to make themselves available for the duration of the study
             and are willing to follow study procedures

          -  Have given written informed consent approved by Lilly and the institutional review
             board (IRB) governing the site

        Exclusion Criteria:

          -  Are currently enrolled in, have completed, or discontinued within the last 30 days
             from, a clinical trial involving an investigational product other than the
             investigational product 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 LY2886721, related compounds, or any components of the
             formulation

          -  Are persons who have previously received the investigational product in this study,
             have completed or withdrawn from this study or any other study investigating LY2886721

          -  Have a Bazett's corrected QT (QTcB) interval value of >450 milliseconds (msec) or any
             abnormality in the 12-lead electrocardiogram (ECG) increases the risks associated with
             participating in the study

          -  Have an abnormal blood pressure

          -  Have a history or presence of cardiovascular, respiratory, hepatic, 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

          -  Show evidence of human immunodeficiency virus (HIV) infection and/or positive HIV
             antibodies

          -  Show evidence of hepatitis C and/or positive hepatitis C antibody

          -  Show evidence of hepatitis B and/or positive hepatitis B surface antigen

          -  Intend to use prescription medication, over-the-counter medication, or herbal
             preparations containing St. John's Wort, kava, garlic, ginger, ginko biloba, or
             guarana within 14 days prior to admission

          -  Eating of grapefruit or grapefruit-containing foods, or drinking grapefruit-containing
             juices within 7 days prior to dosing or any time during the study

          -  Have used any tobacco- or nicotine-containing products (including, but not limited to,
             cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or
             nicotine gum) within 6 months prior to dosing

          -  Have donated blood of more than 500 milliliters (mL) within the last month

          -  Have an average weekly alcohol intake that exceeds 21 units per week (males up to age
             65), or are unwilling to stop alcohol consumption from 48 hours prior to check-in
             until end of study [1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine;
             1.5 oz or 45 mL of distilled spirits]

          -  Show evidence of significant active neuropsychiatric disease, in particular evidence
             of significant medical or psychiatric illness within the past 12 months. Have any
             other condition that would preclude participation in the study

          -  Have a history or presence of epilepsy, a history of seizures, any known brain
             abnormalities, and a history of significant brain injury

          -  Have participated in a [^14C] study within the last 6 months prior to check-in for
             this study. The total exposure from this study and the previous study must be within
             the Code of Federal Regulations (CFR) recommended levels considered safe (per 21 CFR
             361.1), less than 5,000 millirems (mrem)/year whole body annual exposure

          -  Exposure to significant radiation within 12 months prior to dose (for example, serial
             X-ray or computed tomography scans, barium meal, current employment in a job requiring
             radiation exposure monitoring)

          -  Have a history of clinically significant adverse drug reactions or "drug allergy" to
             more than 3 types of systemically administered medications (all penicillins and
             cephalosporins may be considered 1 type of medication for this purpose)

          -  Have a history of, or current, significant ophthalmological disease

          -  Have evidence of active renal disease (for example, diabetic renal disease, polycystic
             kidney disease) or creatinine clearance of <80 milliliters per minute (mL/min) as
             calculated by Cockcroft-Gault equation: Men: (140-age)*weight in kilograms
             (kg)/72*[serum creatinine in milligrams per deciliter (mg/dL)]