Early Phase 1
Completed N=8
Safety and Pharmacokinetics of Sustained-release Depot Tacrolimus: A First-in-human Study
Organ Transplant Rejection · Psoriasis
Source: ClinicalTrials.gov NCT03626714 ↗
Enrolled (actual)
8
Serious AEs
0.0%
Results posted
Jun 2019
Primary outcomePrimary: Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability] — 6; 6; 3; 2 Participants
Summary
This first-in-human study is designed to assess the safety and pharmacokinetic (PK) profile of sustained-release (SR) depot tacrolimus, which will be administered as a single dose of 0.1 mg/kg by subcutaneous (SC) injection in healthy subjects.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability] |
6; 6; 3; 2; 1 | — |
| PRIMARY Drug Concentrations in Blood Samples at Individual Time-points |
0; 0.667; 0.956; 1.30; 1.84; 1.54 | — |
| PRIMARY Mean Blood Concentration-time Curve - Cmax |
1.92 | — |
| PRIMARY Mean Blood Concentration-time Curve - Tmax |
14.3 | — |
| PRIMARY Blood Concentration-time Curve [AUC] |
568 | — |
| PRIMARY Terminal Elimination Half-life [t1/2] |
1100 | — |
Eligibility Criteria
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.
Exclusion Criteria
- Inability or unwillingness of a participant to give written informed consent or comply with study protocol;
- Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness must not be enrolled into this trial;
- Presence of an uncontrolled, unstable clinically significant medical condition that in the opinion of the Investigator may increase the risk to the subject or may interfere with the interpretation of safety and PK evaluations, or could impair the subject's ability to complete the trial, or c
Data sourced from ClinicalTrials.gov (NCT03626714). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.