Organ Transplant RejectionEarly Phase 1NCT03626714
Safety and Pharmacokinetics of Sustained-release Depot Tacrolimus: A First-in-human Study
A Early Phase 1 study testing Sustained Release Injectable Tacrolimus in people with Organ Transplant Rejection and Psoriasis, run by Auritec Pharmaceuticals at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Organ Transplant Rejection, Psoriasis
- What is being tested?
- Sustained Release Injectable Tacrolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Oct 2018to 5 Jan 2019
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, First-in-human, Safety and Pharmacokinetic Study of 1-Month Sustained-Release Injectable Tacrolimus in Healthy Subjects
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.
Read the detailed 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.
- Conditions
- Organ Transplant Rejection, Psoriasis
- Being tested
- Sustained Release Injectable Tacrolimus
- Keywords
- Tacrolimus, Immunosuppressant, Sustained-release, Plexis
- Medical subject headings
- Psoriasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sustained Release Injectable TacrolimusDrug
Long-acting formulation of tacrolimus developed using Auritec's proprietary Plexis drug delivery technology.
| Study group | Role | What they receive |
|---|---|---|
| Sustained Release Tacrolimus | Experimental | All subjects will be treated with a single dose injection of sustained-release Tacrolimus Receives: Drug: Sustained Release Injectable Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 60 days
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.
Measured: 60 days
Mean Blood Concentration-time Curve - Cmax
Maximum observed tacrolimus whole blood concentration
Measured: 60 days
Mean Blood Concentration-time Curve - Tmax
Time to maximum observed tacrolimus whole blood concentration
Measured: 60 days
Blood Concentration-time Curve [AUC]
Area under the concentration-time curve
Measured: 60 days
Terminal Elimination Half-life [t1/2]
The apparent terminal elimination half-life was calculated.
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2018
- Study start16 Oct 2018
- Primary completion5 Jan 2019
- Study completion5 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Organ Transplant RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Auritec Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- George J Atiee, MD, Principal investigator, Worldwide Clinical Trials
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03626714
- Sponsor's protocol ID
- RTB-010
- Other IDs
- U44AI069674
- Status last verified
- Jul 2019
- First submitted
- 31 Jul 2018
- Last updated
- 13 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, First-in-human, Safety and Pharmacokinetic Study of 1-Month Sustained-Release Injectable Tacrolimus in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03626714
- Acronym / sponsor ID
- RTB-010
- Conditions
- Organ Transplant Rejection, Psoriasis
- Keywords
- Tacrolimus, Immunosuppressant, Sustained-release, Plexis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Auritec PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 16 Oct 2018 (actual)
- Primary completion
- 5 Jan 2019 (actual)
- Study completion
- 5 Jan 2019 (actual)
- First posted
- 13 Aug 2018 (actual)
- Results
- Posted 11 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sustained Release Tacrolimus | Experimental | Drug: Sustained Release Injectable TacrolimusAll subjects will be treated with a single dose injection of sustained-release Tacrolimus |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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;
Key exclusion criteria (17 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sustained Release Injectable TacrolimusLong-acting formulation of tacrolimus developed using Auritec's proprietary Plexis drug delivery technology. | Drug | Sustained Release Tacrolimus |
Primary outcome
Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability]
Time frame: 60 days
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).
Drug Concentrations in Blood Samples at Individual Time-points
Time frame: 60 days
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.
Mean Blood Concentration-time Curve - Cmax
Time frame: 60 days
Maximum observed tacrolimus whole blood concentration
Mean Blood Concentration-time Curve - Tmax
Time frame: 60 days
Time to maximum observed tacrolimus whole blood concentration
Blood Concentration-time Curve [AUC]
Time frame: 60 days
Area under the concentration-time curve
Terminal Elimination Half-life [t1/2]
Time frame: 60 days
The apparent terminal elimination half-life was calculated.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George J Atiee, MD principal investigator
Worldwide Clinical Trials
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Sustained Release Injectable Tacrolimus in people with Organ Transplant Rejection and Psoriasis, run by Auritec Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability] (time frame: 60 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2019.