The study will evaluate how genetic profiles respond to LY2216684 and the effect of
Quinidine on the pharmacokinetics (PK) of LY2216684 in a specific genetic profile. Side
effects will be documented.
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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 mIU/mL)
- Have a body weight >50 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,
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 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 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.