A Pharmacokinetic Study of the Coadministration of LY2216684 With Sertraline
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Intervention: LY2216684; Sertraline
Intervention description: po administration; po administration
Intervention MeSH terms: Sertraline
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:

      LY2216684 is being studied as adjunctive treatment for major depressive disorder (MDD) in
      participants who are partial responders to selective serotonin reuptake inhibitors (SSRIs).
      Sertraline is a medication that is widely used to treat MDD and is a known substrate of
      cytochrome P450s (CYP450s), including CYP450 2D6 (CYP2D6), CYP450 2C19 (CYP2C19), CYPP450 3A4
      (CYP3A4), and a modest inhibitor of CYP2D6. Based on the diversity of hepatic metabolic
      clearance pathways for LY2216684 and its elimination by the kidney, it is expected that
      CYP2D6 inhibition by sertraline will not result in a substantial change in the
      pharmacokinetic (PK) profile of LY2216684. LY2216684 is only known to be a moderate inhibitor
      of CYP2C19, so it is unlikely that coadministration of sertraline with LY2216684 will result
      in a clinically meaningful change in the PK of sertraline. This study is being conducted to
      test these hypotheses.
    

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
             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, 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).

          -  Body mass index (BMI) up to 32.0 kilograms per square meter (kg/m^2).

          -  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 and pulse rate (supine position and standing) as determined
             by the investigator.

          -  Are reliable and willing to be available for the duration of the study and willing to
             follow study procedures.

          -  Provided written informed consent approved by Lilly and the institutional review board
             (IRB) governing the site.

        Exclusion Criteria:

          -  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/intolerance to LY2216684, sertraline, 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.

          -  Have a history or presence of the signs and/or symptoms of urinary retention or benign
             prostatic hypertrophy.

          -  Show evidence of significant active neuropsychiatric disease or a history of suicidal
             thoughts or suicide attempt.

          -  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.

          -  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 determined to be unsuitable by the investigator for any reason.