A Study of LY2216684 and Theophylline in Healthy Subjects
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Intervention: LY2216684; Theophylline
Intervention description: 18-mg LY2216684 oral dose; 200-mg theophylline oral dose
Intervention MeSH terms: Theophylline
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The primary objective of this study is to confirm that LY2216684 is not an inhibitor of
      cytochrome P450 1A2 (CYP1A2) in healthy participants using theophylline as a probe substrate
      for the enzyme. Because LY2216684 has been observed to increase heart rate in some healthy
      participants, this study will also assess heart rate when coadministered with theophylline.
    

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 1 month 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 both during the study and for 1 month following the last dose of study
             drug; or are women not of child-bearing potential due to surgical sterilization
             (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause (at least 1
             year without menses or 6 months without menses and a follicle stimulating hormone
             [FSH] >40 mass International Units per milliliter [mIU/mL]).

          -  Have 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 blood sampling as per the protocol.

          -  Have normal sitting blood pressure and pulse rate as determined by the investigator.

          -  Are reliable and willing to be available for the duration of the study and are willing
             to follow study procedures.

          -  Have given written informed consent approved by Lilly and the ethical review board
             (ERB) governing the site.

        Exclusion Criteria:

          -  Are investigator site personnel directly affiliated with this study and their
             immediate families. Immediate family is defined as a spouse, parent, child or sibling,
             whether biological or legally adopted.

          -  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, 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, theophylline, or related compounds.

          -  Are persons who have previously 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.

          -  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 substrates, inducers, or
             inhibitors of cytochrome P450 1A2 (CYP1A2) within 30 days prior to dosing.

          -  Have donated blood of more than 500 mL within the last month.

          -  Have an average weekly alcohol intake that exceeds 14 units per week, or are unwilling
             to stop alcohol consumption for 48 hours prior to check-in in each period and while
             resident at the clinical research unit (CRU) (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 and chocolate 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.