Study of [3H] BMS747158 in Healthy Male Subjects

This Phase I, nonrandomized, open-label study will enroll up to seven healthy male subjects who meet all of the inclusion and none of the exclusion criteria. Subjects will receive 100 (±20) μCi of [3H] BMS747158. Subjects will undergo blood, urine, and fecal collections to evaluate [3H] activity for a minimum of 7 days post-dose. Safety will be assessed by monitoring of adverse events (AEs), vital signs, physical examinations, clinical laboratory tests, and electrocardiograms (ECGs).This Phase I, nonrandomized, open-label study will enroll up to seven healthy male subjects who meet all of the inclusion and none of the exclusion criteria. Subjects will receive 100 (±20) μCi of [3H] BMS747158. Subjects will undergo blood, urine, and fecal collections to evaluate [3H] activity for a minimum of 7 days post-dose. Safety will be assessed by monitoring of adverse events (AEs), vital signs, physical examinations, clinical laboratory tests, and electrocardiograms (ECGs).

Inclusion criteria

• Provide written signed informed consent prior to any study procedures
• Be healthy as determined by no clinically significant deviation from normal in medical history, physical examination, vital signs, ECG, and clinical laboratory tests
• Have a Body Mass Index (BMI) of 18 to 30 kg/m2
• Be male, age 18 to 45 years
• Be sterile or agree to use from admission until discharge one 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 (IUD) with spermicide *a female condom with spermicide contraceptive sponge with spermicide
• an intravaginal system [e.g., NuvaRing®]
• a diaphragm with spermicide
• a cervical cap with spermicide, or
• oral, implantable, transdermal, or injectable contraceptives
• Must be able to communicate effectively with study personnel

Exclusion criteria

• Any significant active or chronic medical illness or acute significant trauma
• History of any condition that may disrupt and/or increase permeability of the blood-brain barrier or diabetes
• History of any neurological disease.
• History of concussion or meningitis within the past 6 months
• History of sleep disorders, including snoring with sleep apnea and narcolepsy
• History of anxiety disorder
• Current or recent GI disease
• Major surgery within 4 weeks
• GI surgery that could impact upon the re-absorption of study drug
• History of chronic constipation
• History of asthma as deemed clinically significant by the Investigator or designee
• History of recent (within 2 weeks of enrollment) infection (e.g., upper respiratory tract infection, urinary tract infection)
• Known and confirmed drug allergies or hypersensitivities
• Donation of blood and/or plasma to a blood bank or in a clinical study (except as required for screening) within four weeks of enrollment
• Blood transfusion within four weeks of enrollment
• Inability to tolerate intravenous medication or unlikely to obtain and/or tolerate venous access
• Past (6 months) or present history of drug or alcohol abuse
• Screening or pre-dose ECG interval abnormalities or organ dysfunction.
• Positive urine screen for drugs of abuse either at screening or before dosing
• Positive blood screen for hepatitis B surface antigen, hepatitis C antibody, or HIV
• Exposure to any investigational drug, device, or placebo within four weeks of enrollment
• Use of any prescription drugs within 4 weeks of enrollment
• Use of any other drugs, including over-the-counter medications (e.g., acid-controllers) and herbal preparations within two weeks of enrollment
• Smoking within 1 month of enrollment
• Alcohol or caffeine consumption within 72 hours of study drug administration
• Participation in a radio-labeled study within 12 months of enrollment
• Intake of radio-labeled drug substance or exposure to significant radiation
• Participation in any prior study with BMS747158