A Study to Evaluate the Effect of Clarithromycin on LY2216684
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Intervention: LY2216684; Clarithromycin
Intervention description: Administered orally; Administered orally
Intervention MeSH terms: Clarithromycin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The study will evaluate the effect of Clarithromycin on the pharmacokinetics (PK) of
      LY2216684 in healthy participants. Side effects will be documented. There will be 2 study
      periods (5 and 9 days) and follow up will occur at least 7 days after the last dose.
      Screening is required within 45 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:

             o Agree to use a reliable method of birth control during the study and for 1 month
             following the last dose of study drug

          -  Female participants:

             o Are women of child-bearing potential who test negative for pregnancy at the time of
             enrollment, have used a reliable method of birth control (not including hormonal
             contraceptives) for 4 weeks prior to administration of study drug, and agree to use a
             reliable method of birth control during the study and for 1 month following the last
             dose of study drug; or women not of child-bearing potential due to surgical
             sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation/occlusion) or
             menopause [at least 1 year without menses or 6 months without menses and a follicle
             stimulating hormone (FSH) >40 milli-international units per milliliter (mIU/mL)]

          -  Have a body weight >50 kilograms (kg)

          -  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 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 institutional review
             board (IRB) governing the site

          -  Have normal blood pressure (BP) and pulse rate (PR) (sitting position) as determined
             by the investigator

          -  Are predicted to have both cytochrome P450 (CYP)2D6 and CYP2C19 extensive metabolizer
             (EM) phenotypes as determined by genotyping assessment

        Exclusion Criteria:

          -  Are currently enrolled in, have completed or discontinued within the last 30 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/intolerance to LY2216684 or clarithromycin, 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 LY2216684
             within 6 months prior to screening

          -  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 a history of/or current 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 a history or show evidence of significant active neuropsychiatric disease or have
             a history of suicide attempt or ideation

          -  Have a documented or suspected history of glaucoma

          -  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 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.
             Exceptions include influenza vaccinations, the use of topical medication (provided
             there is no evidence of chronic dosing with the risk of systemic exposure), occasional
             use of acetaminophen/paracetamol/ibuprofen, hormone replacement therapy including
             thyroid replacement (stable dose for at least 1 month)

          -  Use of known inhibitors and/or inducers of CY2D6, CYP2C19, and/or CYP3A 30 days prior
             to enrollment or are unwilling to avoid them during the study (except for use of
             clarithromycin)

          -  Have donated blood of more than 500 mL within the last month

          -  Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14
             units per week (females), or are unwilling to stop alcohol consumption 48 hours prior
             to dosing in Period 1 until discharge [1 unit = 12 oz (ounces) 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 or foods of comparable caffeine
             content) per day, on a habitual basis, or are unwilling to stop caffeine consumption
             from 48 hours prior to dosing in Period 1 until discharge

          -  Participants unwilling to adhere to the smoking restrictions of the Clinical Research
             Unit (CRU) while a resident of the CRU

          -  Have consumed grapefruit or grapefruit-containing products, starfruit, or pomegranates
             30 days prior to enrollment or are unwilling to avoid them during the study

          -  Participants determined to be unsuitable by the investigator for any reason