A Study of LY2140023 in Healthy Participants
Condition: Healthy Participants
Intervention: LY2140023; 14C-LY2140023; 14C-LY404039
Intervention description: Administered orally.; Administered IV.; Administered IV.
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to assess the extent and rate of absorption of LY2140023 in
      healthy participants. The study has two periods. In Treatment Period 1, participants will
      receive a single oral dose of 80 milligrams (mg) LY2140023 followed by a 2-hour intravenous
      (IV) infusion of approximately 100 micrograms (µg) LY2140023 containing approximately 100
      nanocuries (nCi) [14C]-LY2140023. In Treatment Period 2, participants will receive an oral
      dose of 80 mg LY2140023 followed by a 2-hour IV infusion of approximately 100 µg LY404039
      containing approximately 100 nCi [14C]-LY404039. There will be at least a 3-day washout
      between doses.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are healthy males or females of non-childbearing potential, as determined by medical
             history and physical examination

          -  Male participants: must agree to use a reliable method of birth control during the
             study and for 3 months following the last dose of LY2140023, and agree not to donate
             sperm for 3 months following the last dose of LY2140023

          -  Female participants of non-childbearing potential i.e. postmenopausal or permanently
             sterile following hysterectomy, bilateral salpingectomy or confirmed tubal occlusion
             (not tubal ligation). Postmenopausal is defined as spontaneous amenorrhea for at least
             12 months and a plasma follicle-stimulating hormone (FSH) level >40 million
             international units/milliliter (mIU/mL), unless the participant is taking hormone
             replacement therapy

          -  Have given written informed consent approved by Lilly and the chosen ethical review
             board (ERB)

          -  Have venous access sufficient to allow for intravenous infusion and blood sampling

        Exclusion Criteria:

          -  Are currently enrolled in or have completed or discontinued within the last 90 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 participated in any clinical trial involving a radiolabeled investigational
             product or been exposed to radiolabeled substances (for treatment or diagnosis) within
             the last 12 months

          -  Have known allergies to LY2140023 or LY404039, related compounds, or any components of
             the formulation

          -  Are persons who have previously withdrawn from this study or any other study
             investigating LY2140023 after receiving at least 1 dose of LY2140023

          -  Show evidence or any history of significant active neuropsychiatric disease (for
             example, manic depressive illness, schizophrenia, depression)

          -  Have increased risk of seizures based on a history of:

               -  One or more seizures (except for a single simple febrile seizure [lacking
                  focality, lasting less than 15 minutes, and not associated with a central nervous
                  system (CNS) infection or severe metabolic disturbance] as a child between ages 6
                  months to 5 years)

               -  Head trauma with loss of consciousness or a post-concussive syndrome within 1
                  year or lifetime history of head trauma with persistent neurological deficit
                  (focal or diffuse)

               -  CNS infection, uncontrolled migraine, or transient ischemic attack (TIA) within 1
                  year; stroke with persistent neurological deficit (focal or diffuse),
                  uncontrolled migraine is defined as migraine attacks that produce headache
                  lasting up to 72 hours and are often accompanied by associated symptoms (nausea,
                  photophobia, and phonophobia) that impair well-being and disrupt social
                  functioning. TIA is defined as a "mini-stroke" caused by temporary disturbance of
                  blood supply to an area of the brain, which results in a sudden, brief decrease
                  in brain function

               -  CNS infection with persistent neurological deficit (focal or diffuse)

               -  Brain surgery

               -  Electroencephalogram (EEG) with paroxysmal (epileptiform) activity (isolated
                  spikes waves, repetitive bursts of sharp waves, paroxysmal activity, frank
                  seizures, spike-wave complexes, or sharp-slow wave complexes, or as locally
                  defined)

               -  Brain structural lesion, including developmental abnormalities, as determined by
                  examination or imaging studies (except hydrocephalus treated by shunt and without
                  neurological deficit)

          -  Show evidence of active renal disease (for example, diabetic renal disease, polycystic
             kidney disease) or creatinine clearance less than 80 milliliters/minute (mL/min) as
             determined by the Cockroft Gault formula

          -  Show evidence or any history of known substance dependence or abuse at any time
             (according to Diagnostic and Statistical Manual of Mental Disorders [DSM-IV]
             diagnosis), or regularly use known drugs of abuse and/or show positive findings on
             urinary drug screening

          -  Have a clinically significant abnormality in the neurological examination

          -  Participants judged prior to randomization to be at suicidal risk by the investigator