The purpose of this study is to determine how much lorazepam gets into the blood and how
long it takes the body to get rid of it when given together with LY2216684. Information
about any side effects that may occur will also be collected.
Inclusion Criteria:
- Are overtly healthy, as determined by medical history and physical examination.
- Male subjects - Agree to use a reliable method of birth control during the study and
for 1 month following the last dose of study drug.
- Female subjects - 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 (at least 1 year without
menses or 6 months without menses and a follicle stimulating hormone [FSH] >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 (potassium, magnesium,
and calcium values must be within the normal range).
- Have venous access sufficient to allow blood sampling as per the protocol.
- Have normal blood pressure and pulse rate (sitting position) as determined by the
investigator.
- 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 ethical review board
(ERB) 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, 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, lorazepam, benzodiazepines, 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- Are persons who have previously completed or withdrawn from this study or any other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 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 (including hormonal
contraceptives) within 14 days prior to dosing unless deemed acceptable by the
investigator and Sponsor's medical monitor, except for influenza vaccinations.
- Use of any drugs or substances that are known to be substrates, inducers, or
inhibitors of UGT 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 48 hours prior to each study period and while
resident at the CRU (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).
- Consume 5 or more cups of coffee (or other beverages of comparable caffeine content)
per day, on a habitual basis, or any subjects unwilling to adhere to study caffeine
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 acute narrow angle glaucoma.
- Have Gilbert's Syndrome
- Subjects determined to be unsuitable by the investigator for any reason.
