A Study to Evaluate the Effect of Genotype on LY2216684

The human cytochrome P450 2C19 (CYP2C19) enzyme is a polymorphic enzyme yielding ultrarapid metabolizer, extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer (PM) phenotypes. Enrollment in the study was limited to participants predicted to be CYP2C19 extensive metabolizers or CYP2C19 poor metabolizers, as determined by genotyping analysis.

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 (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 the study drug or; Are 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] level >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 cytochrome P450 (CYP)2C19 extensive metabolizer (EM) or poor metabolizer (PM) phenotypes as determined by genotyping assessment
• Are predicted to have CYP2D6 EM phenotype 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 quinidine, related compounds, or any components of the formulation
• Are persons who have previously received the investigational product in this study or 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 or show evidence of significant active neuropsychiatric disease or have a history of suicide attempt or ideation
• 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
• 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 or during the study 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, and hormone replacement therapy including thyroid replacement (stable dose for at least 1 month).
• Have donated blood of more than 500 milliliters (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 ounces [oz] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
• In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study
• 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 stop caffeine consumption from 48 hours prior to dosing in Period 1 until Discharge
• Have consumed grapefruit or grapefruit-containing products 30 days prior to enrollment or unwilling to abstain during the study
• Have a documented or suspected history of glaucoma
• Participants unwilling to adhere to the smoking restrictions of the Clinical Research Unit (CRU) while a resident of the CRU
• Use of known inhibitors and/or inducers of CYP2C19 and CYP2D6 (with the exception of quinidine per protocol) 30 days prior to enrollment or are unwilling to avoid them during the study.