Safety and Pharmacokinetics of Sustained-release Depot Tacrolimus: A First-in-human Study

Inclusion Criteria

• •Subjects must be able to understand and provide informed consent. A signed informed consent form must be provided before any study assessments are done;
• •Males or females, between 18 and 45 years of age, inclusive;
• •Body mass index must be within the range 18.5 to 32.0 kg/m2, inclusive;
• •Must be in good health, as determined by no clinically significant findings from medical history, vital signs, and 12-lead electrocardiogram (ECG), inclusive of documented absence of QT prolongation;
• •Clinical laboratory evaluations (including clinical chemistry panel \[fasted at least 10 hours\], complete blood count \[CBC\], and urinalysis \[UA\]) must be within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator;
• •Must be negative for autoimmune disorders in the past 3 months and at Screening - participant's medical history will be used for this evaluation;
• •Must not use any immunosuppressant calcineurin inhibitor product other than SR Injectable tacrolimus throughout the dosing period and until after the final visit;
• •Must agree to blood draws throughout the course of the study and venous access sufficient to allow for blood sampling as per the protocol;
• •Must be negative for selected drugs of abuse at Screening and at Check-in (Day -1);
• •Must have a negative hepatitis panel (including hepatitis B surface antigen \[HBsAg\] and hepatitis C virus antibody \[HCV\]) and negative human immunodeficiency virus \[HIV\] antibody screens;
• •Females will be nonpregnant, nonlactating, and either postmenopausal, defined as amenorrhea for at least 1 year and follicle-stimulating hormone levels of 40 mIU/mL or higher; surgically sterile (eg, tubal ligation, hysterectomy, oophorectomy) for at least 90 days prior to Screening; or agree to use, from the time of signing the informed consent or 10 days prior to Check-in on Day -1 of the Inpatient Period until 30 days after Study Discharge, one of the following forms of contraception: nonhormonal intrauterine device (IUD) with spermicide; female condom with spermicide; contraceptive sponge with spermicide; diaphragm with spermicide; cervical cap with spermicide; male sexual partner who agrees to use a male condom with spermicide; or sterile sexual partner; alternatively, women must agree to maintain abstinence (must agree to use a double barrier method if they become sexually active during the study. For all females of childbearing potential, the pregnancy test result must be negative at Screening and Check-in on Day -1 of the Inpatient Period (see Appendix 1). Women must also agree not to douche throughout the dosing period and until after the final visit;
• •Males will either be sterile or agree to use, from Check-in on Day -1 of the Inpatient Period until 90 days following Study Discharge, one of the following approved methods of contraception: male condom with spermicide; sterile sexual partner; or use by female sexual partner of an IUD with spermicide; a female condom with spermicide; a contraceptive sponge with spermicide; an intravaginal system (eg, NuvaRing®); a diaphragm with spermicide; a cervical cap with spermicide; or oral, implantable, transdermal, or injectable contraceptives. Subjects will refrain from sperm donation from Check-in on Day -1 of the Inpatient Period until 90 days following Study Discharge.