Clinical trial NCT01367262: Disposition of Carbon-14-Labeled LY2886721 ([^14C]-LY2886721) Following Oral Administration in Healthy Human Participants
Official title: Disposition of [14C]-LY2886721 Following Oral Administration in Healthy Human Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Absorption
Distribution
Metabolism
Excretion
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-06-07
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This open-label study is being conducted to determine the metabolism and physiological disposition of radiolabeled LY2886721 after a single dose in healthy male participants.


Eligibility criteria: Inclusion Criteria:

* Healthy males as determined by medical history and physical examination
* Males will be sterile (including vasectomy) or if the participant is not sterile and is sexually active, he will agree to use from check-in until 3 months after exit/discharge, 1 of the following approved methods of contraception: a male condom with spermicide, a sterile sexual partner, use by female sexual partner of an intrauterine device with spermicide, a female condom with spermicide, contraceptive sponge with spermicide, a diaphragm with spermicide, a cervical cap with spermicide, or oral, implantable, transdermal, intravaginal, or injectable contraceptives
* Have a body mass index of 19 to 30 kilograms per square meter (kg/m\^2)
* 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
* Have normal blood pressure and heart rate (sitting)
* Experience a minimum of at least 1 bowel movement per day
* 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

Exclusion Criteria:

* Are currently enrolled in, have completed, or discontinued within the last 30 days from, a clinical trial involving an investigational product other than the investigational product used in this study; 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 LY2886721, 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 LY2886721
* Have a Bazett's corrected QT (QTcB) interval value of \>450 milliseconds (msec) or any abnormality in the 12-lead electrocardiogram (ECG) increases the risks associated with participating in the study
* Have an abnormal blood pressure
* Have a history or presence of 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 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
* Intend to use prescription medication, over-the-counter medication, or herbal preparations containing St. John's Wort, kava, garlic, ginger, ginko biloba, or guarana within 14 days prior to admission
* Eating of grapefruit or grapefruit-containing foods, or drinking grapefruit-containing juices within 7 days prior to dosing or any time during the study
* Have used any tobacco- 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 dosing
* 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 up to age 65), or are unwilling to stop alcohol consumption from 48 hours prior to check-in until end of study \[1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits\]
* Show evidence of significant active neuropsychiatric disease, in particular evidence of significant medical or psychiatric illness within the past 12 months. Have any other condition that would preclude participation in the study
* Have a history or presence of epilepsy, a history of seizures, any known brain abnormalities, and a history of significant brain injury
* Have participated in a \[\^14C\] study within the last 6 months prior to check-in for this study. The total exposure from this study and the previous study must be within the Code of Federal Regulations (CFR) recommended levels considered safe (per 21 CFR 361.1), less than 5,000 millirems (mrem)/year whole body annual exposure
* Exposure to significant radiation within 12 months prior to dose (for example, serial X-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring)
* Have a history of clinically significant adverse drug reactions or "drug allergy" to more than 3 types of systemically administered medications (all penicillins and cephalosporins may be considered 1 type of medication for this purpose)
* Have a history of, or current, significant ophthalmological disease
* Have evidence of active renal disease (for example, diabetic renal disease, polycystic kidney disease) or creatinine clearance of \<80 milliliters per minute (mL/min) as calculated by Cockcroft-Gault equation: Men: (140-age)\*weight in kilograms (kg)/72\*\[serum creatinine in milligrams per deciliter (mg/dL)\]

Primary outcomes:
measure: Percentage of Urinary and Fecal Excretion of LY2886721 Radioactivity Over Time
timeFrame: Predose up to 7 days (168 hours) postdose
Secondary outcomes:
measure: Plasma Pharmacokinetics (PK) of LY2886721: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0 to Inf)]
timeFrame: Predose up to 4 days (96 hours) postdose
measure: PK of Radioactivity: AUC(0 to Inf)
timeFrame: Predose up to 4 days (96 hours) postdose
measure: Plasma PK of LY2886721: Maximum Observed Concentration (Cmax)
timeFrame: Predose up to 4 days (96 hours) postdose
measure: PK of Radioactivity: Cmax
timeFrame: Predose up to 4 days (96 hours) postdose
measure: Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma
timeFrame: 1 to 8 hours postdose
measure: Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Urine
timeFrame: 0 to 72 hours postdose
measure: Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Feces
timeFrame: 0 to 144 hours postdose
Other outcomes:
Locations:
city: Madison
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Wisconsin
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 am - 5 pm Eastern Time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: