A Study to Measure if There is Any Difference in How the Body Breaks Down or Inactivates Either Fluoxetine or LY2216684 When Both of These Medicines Are Given Together.
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Intervention: LY2216684; Fluoxetine
Intervention description: LY2216684: 18 mg po QD on Days 1, 2, and 3 and Days 25-27; Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27)
Intervention MeSH terms: Fluoxetine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to measure if there is any difference in how the body breaks
      down or inactivates either fluoxetine or LY2216684 when both of these medicines are given
      together. This study will look at how fluoxetine might affect LY2216684 and how giving
      LY2216684 might affect fluoxetine in the body.

      The duration of study participation in this study is approximately 36 days not including the
      screening appointment. This study requires 1 research unit confinement of 29 days/28 nights
      followed by 1 outpatient appointment. A screening appointment is required within 30 days
      prior to the start of the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are overtly healthy as determined by medical history and physical examination.

          -  Male participants: Agree to use a reliable method of birth control during the study +
             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, have used a reliable method of birth control for
             6 weeks prior to administration of study drug, and agree to use a reliable method of
             birth control during the study + 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 a follicle stimulating hormone (FSH) level ≥40
             mass International Units per milliliter (mIU/mL).

          -  Are between the ages of 18-65 years, inclusive.

          -  Are between the body mass index (BMI) of 18.5-32.0 kilograms per square meter
             (kg/m^2), inclusive.

          -  Have screening 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 blood sampling according to the protocol.

          -  Have normal blood pressure (BP) and pulse rate (supine position and standing) as
             determined by the investigator.

          -  Are reliable and available for the duration of the study and are willing to follow
             study procedures.

          -  Provided written informed consent approved by Lilly and the institutional review board
             (IRB) governing the site.

        Exclusion Criteria:

          -  Are investigator site personnel directly affiliated with this study or their immediate
             families. Immediate family is defined as a spouse, parent, child or sibling, whether
             biological or legally adopted.

          -  Are Lilly employees.

          -  Are currently enrolled in, or discontinued within the last 30 days from, a clinical
             trial involving an investigational 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, fluoxetine, or related compounds.

          -  Are persons who previously completed or discontinued from this study, or any other
             study investigating LY2216684 within 6 months prior to screening.

          -  Have a clinically significant abnormality in the 12-lead electrocardiogram (ECG) as
             determined by the investigator.

          -  Have significant history of or current cardiovascular (including dysrhythmias),
             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 a history of seizure disorders.

          -  Have a history or presence of the signs and/or symptoms of hyponatremia.

          -  Have a history or presence of the signs and/or symptoms of hyperthyroidism as
             determined by an abnormal thyroid stimulating hormone (TSH) at screening.

          -  Show evidence of significant active neuropsychiatric disease or a history of suicidal
             thoughts or attempted suicide.

          -  Regularly use known drugs of abuse and/or show positive findings on urinary drug
             screening.

          -  Show evidence of human immunodeficiency virus (HIV) 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 or prescription medication within 14 days prior to
             dosing, unless deemed acceptable by the investigator and sponsor's medical monitor.

          -  Use of any drugs or substances that are known to be a strong inducer or inhibitor of
             cytochrome P450 2D6 (CYP2D6) within 30 days prior to check-in.

          -  Have donated blood of more than 500 milliliters (mL) within 4 weeks prior to
             screening.

          -  Have an average weekly alcohol intake that exceeds 14 units per week, or are unwilling
             to stop alcohol consumption 48 hours prior to check-in until the completion of the
             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).

          -  Consume 5 or more cups of coffee (or other beverages of comparable caffeine content)
             per day, on a habitual basis, or any participants unwilling to adhere to study
             caffeine restrictions.

          -  Have used any tobacco-containing 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 enrollment.

          -  Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment
             and during the study.

          -  Have a documented or suspected history of glaucoma.

          -  Participants are determined to be unsuitable by the investigator for any reason.