Effect of P-glycoprotein Inhibition on Lenalidomide Pharmacokinetics in Healthy Males

Inclusion Criteria:

• Must understand and voluntarily sign a written informed consent form prior to any study-related procedures being performed.
• Must be able to communicate with the investigator, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules.
• Healthy male volunteer of any race between 18 to 65 years of age (inclusive), and in good health as determined by a physical exam.
• Agree to use barrier contraception (i.e., condoms not made of natural (animal) membrane [e.g., latex or polyurethane condoms are acceptable]) when engaging in sexual activity with a female of child-bearing potential while on study drug, and for at least 90 days after the last dose of study drug.
• Must have a body mass index between 18 and 33 kg/m2 (inclusive).
• Clinical laboratory tests must be within normal limits or acceptable to the principal investigator.
• Must have confirmation of normal renal function (defined as an estimate glomerular filtration rate >90 mL/min).
• Must be afebrile, with supine systolic blood pressure: 90 to 140 mmHg, supine diastolic blood pressure: 60 to 90 mmHg, and pulse rate: 40 to 110 bpm.
• Must have a normal or clinically acceptable 12-lead electrocardiogram, with a QTcF (Fridericia's correction formula) value ≤ 430 msec.
• Must refrain from sperm donations for the entire duration of the study, and for at least 90 days after the last dose of study drug.

Exclusion Criteria:

• History of any clinically significant and relevant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, known hypersensitivity to a member of the class of immunomodulatory drugs (IMiDs®), temosirolimus, sirolimus, polysorbate 80, diphenhydramine, or to any other component (or excipients) of Torisel®, or other major disorders.
• Any condition which places the subject at unacceptable risk if he were to participate in the study, or confounds the ability to interpret data from the study.
• Used any prescribed systemic or topical medication within 30 days of the first dose administration, unless Sponsor agreement is obtained.
• Used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration, unless Sponsor agreement is obtained.
• Used any prescribed, or non-prescribed, systemic or topical medication that is a CYP3A inhibitor or inducer within 30 days of first dose administration. (refer to (http://medicine.iupui.edu/clinpharm/ddis/p450_Table_Oct_11_2009.pdf)
• Has any surgical or medical conditions (excluding appendectomy) possibly affecting drug absorption, distribution, metabolism and excretion, e.g., bariatric procedure.
• Donated blood or plasma within 8 weeks before the first dose administration to a blood bank or blood donation center.
• History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual within 2 years before dosing, or positive drug screening test reflecting consumption of illicit drugs.
• History of alcohol abuse (as defined by the current version of the Diagnostic and Statistical Manual) within 2 years before dosing, or positive alcohol screen.
• Known to have serum hepatitis or known to be a carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb), or have a positive result to the test for HIV antibodies at Screening.
• Exposed to an investigational drug (new chemical entity) within 30 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer).
• For Part 2 only: has total bilirubin ≥ 1.5x upper limit of normal