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

Psoriasis Clinical Trial

Official title:

An Open-Label, First-in-human, Safety and Pharmacokinetic Study of 1-Month Sustained-Release Injectable Tacrolimus in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03626714
• Other study ID #: RTB-010
• Secondary ID: U44AI069674
• Status: Completed
• Phase: Early Phase 1
• Start date: October 16, 2018
• Est. completion date: January 5, 2019

Study information

• Verified date: July 2019
• Source: Auritec Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a first-in-human study to assess the safety and pharmacokinetic (PK) profile of sustained-release (SR) tacrolimus, which will be administered as a single dose of 0.1 mg/kg by subcutaneous (SC) injection in healthy subjects.

The short-term general investigational plan is to evaluate sustained release tacrolimus in healthy volunteers for up to 30 days in an exploratory trial to determine safety and drug concentrations in blood. The results from this study will inform the long-term goal of this program, which is to provide an improved treatment modality for prophylaxis of organ (kidney, liver and heart) transplant rejection with the additional benefit of enhancing medication compliance. These improvements have the potential to mitigate both the personal and economic burden of this disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: January 5, 2019
• Est. primary completion date: January 5, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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 could impair the decisional capacity of the subject;

• Presence of clinically significant vital signs or a physical examination finding that, in the opinion of the Investigator, could increase the risk to the subject or may potentially interfere with the ability to evaluate safety and tolerability in the trial;

• History of tacrolimus use, or hypersensitivity and/or adverse reaction to calcineurin inhibitor drugs;

• History of toxic shock syndrome;

• Currently receiving chemotherapy or immunosuppressive agents;

• Use of investigative drugs within 30 days or 5 half-lives of study participation;

• Currently using sirolimus;

• Currently using live vaccines;

• Currently on concomitant substrates and/or inhibitors of CYP3A4;

• Requires the use of any concomitant medication, except for treatment of an adverse event (AE) during the study;

• Any abnormality on clinical laboratory tests, or ECG finding that is considered to be clinically significant by the Investigator.

• Known or suspected (nonfebrile) seizure disorder;

• Use of any other depot medications within the last three months.

• Unwilling to commit to avoid eating grapefruit or drinking grapefruit juice during the first 30 days of this exploratory study.

• Grade = 1 finding as described in the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials

Related Conditions & MeSH terms

• Organ Transplant Rejection
• Psoriasis

Intervention

Drug:
• Sustained Release Injectable Tacrolimus
Long-acting formulation of tacrolimus developed using Auritec's proprietary Plexis drug delivery technology.

Locations

Country	Name	City	State
United States	Worldwide Clinical Trials	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Auritec Pharmaceuticals	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability]	Adverse events were documented at each study visit according to the criteria set forth in the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening).	60 days
Primary	Drug Concentrations in Blood Samples at Individual Time-points	The concentrations of tacrolimus in blood samples were measured at baseline, day 1 (1 hr, 3 hrs, 6 hrs, 12 hrs, and 24 hrs), followed by days 3, 7, 14, 21, 30, 37, 44, 51 and 60.	60 days
Primary	Mean Blood Concentration-time Curve - Cmax	Maximum observed tacrolimus whole blood concentration	60 days
Primary	Mean Blood Concentration-time Curve - Tmax	Time to maximum observed tacrolimus whole blood concentration	60 days
Primary	Blood Concentration-time Curve [AUC]	Area under the concentration-time curve	60 days
Primary	Terminal Elimination Half-life [t1/2]	The apparent terminal elimination half-life was calculated.	60 days