A Study of LY2140023 in Healthy Males and Females
Condition: Healthy Volunteers
Intervention: LY2140023 Reference form; LY2140023 Test-Low; LY2140023 Test-Medium; LY2140023 Test-High
Intervention description: 80-mg tablet administered orally; 80-mg tablet administered orally; 80-mg tablet administered orally; 80-mg tablet administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The study will evaluate the effect of different particle size of LY2140023. The study
      involves 4 single doses of 80 milligrams (mg) LY2140023 taken as 1 tablet by mouth with a
      washout period of at least 3 days between doses. This study will last approximately 60 days
      not including screening. Screening is required within 30 days prior to study entry.
    

Eligibility criteria:

        Inclusion Criteria:

          -  are overtly healthy males or females, as determined by medical history and physical
             examination

          -  male participants: 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:

               -  female participants of child-bearing potential who test negative for pregnancy at
                  screening and agree to use a reliable method of birth control for the duration of
                  the study and for at least 3 months after the last dose of LY2140023

               -  female participants who are of non-childbearing potential (that is,
                  postmenopausal or permanently sterile following hysterectomy, bilateral
                  salpingectomy, or confirmed tubal occlusion [not tubal ligation]). Postmenopausal
                  is defined as no menses for at least 1 year, or a plasma follicle stimulating
                  hormone (FSH) value of >40 milli-international units per liter (mIU/mL), unless
                  the participant is taking hormone replacement therapy

          -  have a body mass index (BMI) of 19 to 32 kilograms per meter squared (kg/m^2),
             inclusive, at the time of screening

          -  have clinical laboratory test results within normal reference ranges 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 as per the protocol

          -  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 chosen ethical review
             board (ERB)

        Exclusion Criteria:

          -  are currently enrolled in or have completed or discontinued within the last 90 days
             from a clinical trial involving an investigational product, 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 LY2140023, LY404039, related compounds, or any components of
             the formulation

          -  are persons who have previously completed or withdrawn from this study or any other
             study investigating LY2140023 and have previously received the investigational product

          -  have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the
             investigator, increases the risks associated with participating in the study

          -  have an abnormal blood pressure or pulse rate as determined by the investigator

          -  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

          -  have evidence or any history of significant active neuropsychiatric disease

          -  have increased risk of seizures based on a history of:

               -  one or more seizures (except for a single simple febrile seizure [lacking
                  focality and lasting less than 15 minutes, 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)

               -  uncontrolled migraine or transient ischemic attack (TIA) within 1 year and/or
                  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 "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 or without
                  neurological deficits).

          -  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

          -  show evidence of human immunodeficiency (HIV) virus infection and/or positive human
             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

          -  are women with a positive pregnancy test or women who are lactating

          -  intend to use over-the-counter (OTC) or prescription medication within 14 days prior
             to dosing of LY2140023

          -  have donated blood of more than 500 milliliters (mL) within the 3 months prior to
             screening, or plan to donate blood within the 3 months after the last dose

          -  have an average weekly alcohol intake that exceeds 28 units per week (males) and 21
             units per week (females), or are unwilling to stop alcohol consumption for 48 hours
             prior to check-in for each treatment period until discharge in each period (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)

          -  have a clinically significant abnormality in the neurological examination

          -  participants judged prior to randomization to be at suicidal risk by the investigator

          -  participants who are unwilling to refrain from tobacco- or nicotine-containing
             products while in the Clinical Research Unit (CRU) or are unable to abide by CRU
             restrictions

          -  show evidence of pruritus or skin exfoliation

          -  have an eosinophil count > 1.5 x 10^9 per liter (L)

          -  show evidence of active renal disease or creatinine clearance (CrCl) less than 90
             milliliters per minute (mL/min) (as calculated by the Cockcroft-Gault equation)

          -  in the opinion of the investigator or sponsor, are unsuitable for inclusion in the
             study