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.

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.

During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.