Trial Outcomes & Findings for Safety and Pharmacokinetics of Sustained-release Depot Tacrolimus: A First-in-human Study (NCT NCT03626714)
NCT ID: NCT03626714
Last Updated: 2019-08-13
Results Overview
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).
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
8 participants
Primary outcome timeframe
60 days
Results posted on
2019-08-13
Participant Flow
Participant milestones
| Measure |
Experimental: Sustained Release Injectable Tacrolimus
All subjects will be treated with a single dose injection of sustained-release Tacrolimus.
|
|---|---|
|
Overall Study
STARTED
|
8
|
|
Overall Study
COMPLETED
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Pharmacokinetics of Sustained-release Depot Tacrolimus: A First-in-human Study
Baseline characteristics by cohort
| Measure |
Experimental: Sustained Release Injectable Tacrolimus
n=8 Participants
All subjects will be treated with a single dose injection of sustained-release Tacrolimus.
|
|---|---|
|
Age, Continuous
|
34.37 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 60 daysAdverse 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).
Outcome measures
| Measure |
Experimental: Sustained Release Injectable Tacrolimus
n=8 Participants
All subjects were subcutaneously injected a single dose (0.1 mg/kg) of sustained-release tacrolimus.
|
|---|---|
|
Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability]
Tenderness at Injection Site - Grade 1
|
6 Participants
|
|
Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability]
Burning Pain at Injection Site - Grade 1
|
6 Participants
|
|
Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability]
Erythema/Redness at Injection Site - Grade 1
|
3 Participants
|
|
Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability]
Induration/Swelling at Injection Site - Grade 1
|
2 Participants
|
|
Number of Subjects That Experienced Treatment-related Adverse Events [Safety and Tolerability]
Tenderness at Injection Site - Grade 2
|
1 Participants
|
PRIMARY outcome
Timeframe: 60 daysThe 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.
Outcome measures
| Measure |
Experimental: Sustained Release Injectable Tacrolimus
n=8 Participants
All subjects were subcutaneously injected a single dose (0.1 mg/kg) of sustained-release tacrolimus.
|
|---|---|
|
Drug Concentrations in Blood Samples at Individual Time-points
Baseline
|
0 ng/mL
Standard Deviation 0
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 1, hour 1
|
0.667 ng/mL
Standard Deviation 0.505
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 1, hour 3
|
0.956 ng/mL
Standard Deviation 0.556
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 1 hour 6
|
1.30 ng/mL
Standard Deviation 0.623
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 1, hour 12
|
1.84 ng/mL
Standard Deviation 0.548
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 1, hour 24
|
1.54 ng/mL
Standard Deviation 0.484
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 3
|
1.24 ng/mL
Standard Deviation 0.397
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 7
|
0.775 ng/mL
Standard Deviation 0.365
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 14
|
0.341 ng/mL
Standard Deviation 0.158
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 21
|
0.320 ng/mL
Standard Deviation 0.127
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 30
|
0.302 ng/mL
Standard Deviation 0.091
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 37
|
0.282 ng/mL
Standard Deviation 0.074
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 44
|
0.260 ng/mL
Standard Deviation 0.082
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 51
|
0.269 ng/mL
Standard Deviation 0.091
|
|
Drug Concentrations in Blood Samples at Individual Time-points
Day 60
|
0.260 ng/mL
Standard Deviation 0.072
|
PRIMARY outcome
Timeframe: 60 daysMaximum observed tacrolimus whole blood concentration
Outcome measures
| Measure |
Experimental: Sustained Release Injectable Tacrolimus
n=8 Participants
All subjects were subcutaneously injected a single dose (0.1 mg/kg) of sustained-release tacrolimus.
|
|---|---|
|
Mean Blood Concentration-time Curve - Cmax
|
1.92 ng/mL
Standard Deviation 0.527
|
PRIMARY outcome
Timeframe: 60 daysTime to maximum observed tacrolimus whole blood concentration
Outcome measures
| Measure |
Experimental: Sustained Release Injectable Tacrolimus
n=8 Participants
All subjects were subcutaneously injected a single dose (0.1 mg/kg) of sustained-release tacrolimus.
|
|---|---|
|
Mean Blood Concentration-time Curve - Tmax
|
14.3 Hour
Standard Deviation 6.36
|
PRIMARY outcome
Timeframe: 60 daysArea under the concentration-time curve
Outcome measures
| Measure |
Experimental: Sustained Release Injectable Tacrolimus
n=8 Participants
All subjects were subcutaneously injected a single dose (0.1 mg/kg) of sustained-release tacrolimus.
|
|---|---|
|
Blood Concentration-time Curve [AUC]
|
568 hour*ng/mL
Standard Deviation 171
|
PRIMARY outcome
Timeframe: 60 daysThe apparent terminal elimination half-life was calculated.
Outcome measures
| Measure |
Experimental: Sustained Release Injectable Tacrolimus
n=8 Participants
All subjects were subcutaneously injected a single dose (0.1 mg/kg) of sustained-release tacrolimus.
|
|---|---|
|
Terminal Elimination Half-life [t1/2]
|
1100 hours
Standard Deviation 803
|
Adverse Events
Experimental: Sustained Release Injectable Tacrolimus
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Experimental: Sustained Release Injectable Tacrolimus
n=8 participants at risk
All subjects were subcutaneously injected a single dose (0.1 mg/kg) of sustained-release tacrolimus.
|
|---|---|
|
Blood and lymphatic system disorders
Elevated Bilirubin
|
25.0%
2/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
Blood and lymphatic system disorders
Decreased Hemoglobin
|
37.5%
3/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
Blood and lymphatic system disorders
Decreased Platelets
|
12.5%
1/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
Gastrointestinal disorders
Elevated Alt/Ast
|
12.5%
1/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
Gastrointestinal disorders
Elevated Aspartate
|
37.5%
3/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
Blood and lymphatic system disorders
Hypercalcemia
|
12.5%
1/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
Renal and urinary disorders
Hematuria
|
12.5%
1/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
General disorders
Hyperglycemia
|
37.5%
3/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
General disorders
Hypoglycemia
|
12.5%
1/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
Renal and urinary disorders
Hypokalemia
|
12.5%
1/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
Blood and lymphatic system disorders
Hyponatremia
|
12.5%
1/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
General disorders
Bruising
|
12.5%
1/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
|
Musculoskeletal and connective tissue disorders
Odontalgia left upper wisdom tooth
|
12.5%
1/8 • For this single-dose experimental study, adverse event data was collected from subjects for up to 60 days.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place