A Study of LY2216684 in Major Depressive Disorder in Patients Taking Selective Serotonin Reuptake Inhibitors
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: LY2216684; Placebo
Intervention description: Administered orally; Administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the effect of LY2216684 on heart rate and blood
      pressure in research participants with MDD who are being treated with an SSRI (selective
      serotonin reuptake inhibitors). Information about any side effects that may occur will also
      be collected. The duration of participation in this study is approximately 24 days not
      including the screening visit. This study requires 1 clinic confinement of 17 days/16 nights
      and 1 Follow-up Outpatient Visit. A screening visit is required within 30 days prior to the
      start of the study. In both periods 1 and 2, the study involves 4 single daily doses of 18 mg
      LY2216684 or placebo taken as 2 tablets by mouth. In period 3, the study involves four single
      daily doses of 36 mg LY2216684 or placebo taken as 4 tablets by mouth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are patients that have been diagnosed with major depressive disorder (MDD) and are on
             a stable dose of an selective serotonin reuptake inhibitor (SSRI) for at least 4 weeks
             prior to enrollment, as determined by medical history and physical examination.

          -  Male patients: Agree to use a reliable method of birth control during the study and
             for 3 months following the last dose of study drug.

          -  Female patients: 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 and for 1 month following the last dose of study drug; or
             Women not of child-bearing potential due to surgical sterilization (hysterectomy or
             bilateral oophorectomy or tubal ligation) or menopause for at least 1 year without
             menses or 6 months without menses and a follicle stimulating hormone (FSH) >40
             milli-international-units/milliliter (mIU/mL).

          -  Have a body mass index (BMI) of up to 32.0 kilogram/squaremeter (kg/m2).

          -  Have normal blood pressure (BP) and pulse rate (systolic BP <140, diastolic BP <90;
             supine position and standing) as determined by the investigator.

          -  Patients that have a diagnosis of hypertension but are well controlled on a stable
             dose (at least 4 weeks of diuretic, angiotensin converting enzyme [ACE]-inhibitor, or
             angiotensin 2 receptor inhibitor) are acceptable for inclusion in this study.
             Allowance of a specific anti-hypertensive is per the investigator's discretion.

          -  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 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.

        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 to any compound related to LY2216684.

          -  Are persons who have previously completed or withdrawn from this study or any other
             study investigating LY2216684.

          -  Have a clinically significant 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 significant history of or presence of cardiovascular (including dysrhythmias),
             respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or
             neurological disorders, or any condition 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 unequal BP (> 20 millimeter of mercury [mm Hg]) in the left arm versus right arm
             (as measured with a BP cuff) or have absent or unequal radial pulses in either arm.

          -  Have a history of seizure disorders.

          -  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.

          -  Use of over-the-counter or prescription medication (other than stable doses of SSRI as
             noted above) with a narrow therapeutic index (including, but not limited to warfarin
             or clopidogrel) or those that are known to have an effect on heart rate (e.g.,
             beta-blockers) within 14 days prior to dosing.

          -  Use of any drugs or substances that are known to be a strong inducer or inhibitor of
             cytochrome P450 2D6 (CYP2D6) or cytochrome P450 3A4 (CYP3A4) within 30 days prior to
             check-in (study entry) and during the conduct of the study.

          -  Have donated blood of more than 500 milliliter (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 (study entry)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 patients unwilling to adhere to study caffeine
             restrictions.

          -  Patients must adhere to the smoking restrictions of the Clinical Research Unit (CRU)
             while a resident of the CRU.

          -  Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment
             or are unwilling to avoid during the study.

          -  Have a documented or suspected history of glaucoma.

          -  Patients determined to be unsuitable by the investigator for any reason.