Disposition of Carbon-14-Labeled LY2886721 ([^14C]-LY2886721) Following Oral Administration in Healthy Human Participants

Healthy Volunteers Clinical Trial

Official title:

Disposition of [14C]-LY2886721 Following Oral Administration in Healthy Human Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01367262
• Other study ID #: 13736
• Secondary ID: I4O-MC-BACD
• Status: Completed
• Phase: Phase 1
• Start date: June 2011
• Est. completion date: July 2011

Study information

• Verified date: May 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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)]

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• LY2886721
Administered orally

Locations

Country	Name	City	State
United States	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.	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Urinary and Fecal Excretion of LY2886721 Radioactivity Over Time	Urinary and fecal excretion of LY2886721 radioactivity over time was expressed as a percentage of the total radioactive dose administered. The amount of drug-related material excreted in urine and feces (Ae) at a specific collection interval (i) was calculated as the product of radioactivity concentration and volume or weight. The Ae values for each collection interval were then summed and calculated as Total Ae=Ae(i1)+Ae(i2)+Ae(in). The percentage of the total radiolabeled dose administered that was excreted in feces or urine=[(Total Ae)/(Total radioactive dose administered)]*100.	Predose up to 7 days (168 hours) postdose
Secondary	Plasma Pharmacokinetics (PK) of LY2886721: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0 to Inf)]		Predose up to 4 days (96 hours) postdose
Secondary	PK of Radioactivity: AUC(0 to Inf)	AUC(0 to inf) for plasma and whole blood total radioactivity is reported as hours*nanogram equivalents per milliliter (h*ng Eq/mL).	Predose up to 4 days (96 hours) postdose
Secondary	Plasma PK of LY2886721: Maximum Observed Concentration (Cmax)		Predose up to 4 days (96 hours) postdose
Secondary	PK of Radioactivity: Cmax	The Cmax of total radioactivity in plasma and whole blood are reported as nanogram equivalents per milliliter (ng Eq/mL).	Predose up to 4 days (96 hours) postdose
Secondary	Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma	The metabolites of LY2886721 were identified using a high performance liquid chromatography (HPLC) chromatogram. The relative abundance of LY2886721 and its metabolites in plasma were reported as a percentage of recovered radioactivity and calculated by dividing the sum of the radioactive content of fractions contributing to a particular peak by the sum of the radioactive content of all fractions in the radio chromatogram, then multiplying by 100. Radioactivity corresponds to 80 µCi [^14C]-LY2886721.	1 to 8 hours postdose
Secondary	Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Urine	The metabolites of LY2886721 were identified using an HPLC chromatogram. The relative abundance of LY2886721 and its metabolites in urine were reported as a percentage of recovered radioactivity and calculated by dividing the sum of the radioactive content of fractions contributing to a particular peak by the sum of the radioactive content of all fractions in the radio chromatogram, then multiplying by 100. Radioactivity corresponds to 80 µCi [^14C]-LY2886721.	0 to 72 hours postdose
Secondary	Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Feces	The metabolites of LY2886721 were identified using an HPLC chromatogram. The relative abundance of LY2886721 and its metabolites in feces were reported as a percentage of recovered radioactivity and calculated by dividing the sum of the radioactive content of fractions contributing to a particular peak by the sum of the radioactive content of all fractions in the radio chromatogram, then multiplying by 100. Radioactivity corresponds to 80 µCi [^14C]-LY2886721.	0 to 144 hours postdose