Complication of Transplant
Conditions
Keywords
bioequivalence, tacrolimus, transplant, CYP3A5 expressors/non expressors
Brief summary
The prospective study will compare the relative bioavailability at steady-state pharmacokinetics of 6 tacrolimus formulations in a prospective, 6-way cross-over study including CYP3A5 expressors (n=30) and non-expressor (n=30) transplant patients.
Detailed description
Comparison of the relative bioavailability and steady-state pharmacokinetics of 6 tacrolimus formulations in a prospective, 6-way cross-over study including CYP3A5 expressors (n=30) and non-expressor (n=30) transplant patients. Six tacrolimus formulations will be tested and each patient will receive each formulation once. As we proposed to test bioequivalence in the steady-state, patients will receive the test formulations for one week prior to pharmacokinetic evaluation. The pharmacokinetic evaluation will incorporate limited sampling strategies with a focus on fully characterizing the Cmax out to hour 4 post dose. Subsequent PK sampling and trough blood concentrations will be monitored on a daily basis using dried blood spots that the study subjects will collect by themselves at home. It will be critical that the patients are adherent to their test medication to ensure that they have reached steady state. This will be monitored using test diaries, pill counts and MEMS caps (Medication Event Monitoring System (MEMS), AARDEX Corp, Palo Alto, CA. Bioequivalence will be tested using average bioequivalence metrics. A combination of limited sampling strategy and dry spot analysis in combination with population pharmacokinetic modeling will be utilized to fully characterize the PK profile of these formulations.
Interventions
DRUGPrograf
Administration of each formulation will be determined by sequence.
DRUGTacrolimus, Sandoz
Administration of each formulation will be determined by sequence.
DRUGTacrolimus, Reddy Laboratory
Administration of each formulation will be determined by sequence.
DRUGTacrolimus, Mylan
Administration of each formulation will be determined by sequence.
DRUGTacrolimus, Accord
Administration of each formulation will be determined by sequence.
DRUGTacrolimus, Pancea Biotech Limited
Administration of each formulation will be determined by sequence.
Sponsors
University of Colorado, Denver
Children's Hospital Medical Center, Cincinnati
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years or older 2. Able to participate and willing to give written informed consent/ assent/ consent by parent or legal guardian and to comply with the study visits and restrictions. 3. Subject who has received a primary or secondary transplant. 4. Subject who is at least 6 months post-transplant and on a stable dose of tacrolimus as defined by physician, one tacrolimus trough level within the physician defined target range within past 6 months and one additional trough level during the screening period within 30% of the physician defined target range. 5. BMI less than or equal to 40.
Exclusion criteria
1. Evidence of any acute rejection 2. Subjects who require dialysis within 6 months prior to study entry 3. Recipients of multiple organ transplants 4. Subjects who have tested positive for HBsAG or HIV, or who are recipients of organ from donors who are known to be HBsAG or HIV positive. Virology screening at the time of transplant. 5. HepC positive subjects with liver biopsy proven recurrent disease considered relevant by physician oversight. 6. Subjects with any severe medical condition requiring acute or chronic treatment that in the investigator's opinion would interfere with study participation 7. History of malignancy, treated or untreated, with the past 2 years with the exception of carcinoma in situ or excised basal cell carcinoma, or hepatocellular carcinoma prior to transplant. 8. GFR ≤ 35 ml/min measured as estimated using the MDRD4 formula 9. Subjects with AST, ALT, total bilirubin ≥ 3 X ULN or other evidence of severe liver disease 10. Subjects with white blood cell (WBC) count ≤2,000/ mm3 or with thrombocytopenia (platelet count ≤ 75,000/ mm3), with an absolute neutrophil count of ≤ 1,500/ mm3 or hemoglobin \<8g/dL) 11. Subjects with clinically significant infections, requiring therapy, which, in the investigator's opinion, would interfere with the objectives of the study 12. Other mental or physical conditions which in the investigator's opinion, are considered clinically significant 13. Presence of intractable immunosuppressant complications or side effects resulting in dose adjustment of tacrolimus 14. Subjects who have been exposed to an investigational therapy within 30 days prior to enrollment or 5 half-lives of the investigational product, whichever is greater. 15. An anticipated change in the immunosuppressive regimen during subject participation other than that required by the protocol 16. Subject with severe GI disturbance or diarrhea which could interfere with tacrolimus absorption 17. Severe diabetic gastroparesis 18. Initiation of any medications that could interfere with tacrolimus blood levels, including OTC medications, herbal supplements, grapefruit or grapefruit juice. 19. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive BhCG laboratory test (\> 5 mIU/mL) 20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are: 1) women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner; 2)women whose partners have been sterilized by vasectomy or 3)using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs); periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Whole blood samples were collected immediately prior to dosing, at 1, 1.5, 1.75, 2, 2.5, 3 and 4 hours following dosing. Subjects were then instructed to performed fingersticks using dried blood spot cards at 8 and 12 hours post dose. | Report the geometric mean and 95% confidence interval for AUC 0-12hr (ng\*hr/ml) for each formulation in expressor and non expressor transplant recipients |
| Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Whole blood samples were collected immediately prior to dosing, at 1, 1.5, 1.75, 2, 2.5, 3 and 4 hours following dosing. Subjects were then instructed to performed fingersticks using dried blood spot cards at 8 and 12 hours post dose. | Report the geometric mean and 95% confidence interval for Cmax (ng/ml) for each formulation in expressor and non expressor transplant recipients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Assessed at baseline and weekly for 6 weeks at each pharmacokinetic profile | Conduct safety lab testing specific to transplanted organ function and clinical assessments for adverse events. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Expressors Subjects with at least one \*1 allele of CYP3A5 | 26 |
| Non-expressors Subjects homozygous for the \*3 CYP3A5 allele | 27 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost venous access | 1 | 0 |
| Overall Study | Protocol Violation | 7 | 7 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Expressors | Total | Non-expressors |
|---|---|---|---|
| Age, Continuous | 55.5 years | 56.25 years | 57 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 13 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 40 Participants | 26 Participants |
| Region of Enrollment United States | 26 participants | 53 participants | 27 participants |
| Sex: Female, Male Female | 10 Participants | 23 Participants | 13 Participants |
| Sex: Female, Male Male | 16 Participants | 30 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 53 | 0 / 53 | 0 / 53 | 0 / 53 | 0 / 53 |
| other Total, other adverse events | 22 / 53 | 14 / 53 | 20 / 53 | 22 / 53 | 23 / 53 | 13 / 53 |
| serious Total, serious adverse events | 0 / 53 | 0 / 53 | 0 / 53 | 0 / 53 | 0 / 53 | 0 / 53 |
Outcome results
Primary
Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients
Report the geometric mean and 95% confidence interval for AUC 0-12hr (ng\*hr/ml) for each formulation in expressor and non expressor transplant recipients
Time frame: Whole blood samples were collected immediately prior to dosing, at 1, 1.5, 1.75, 2, 2.5, 3 and 4 hours following dosing. Subjects were then instructed to performed fingersticks using dried blood spot cards at 8 and 12 hours post dose.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Accord | 112.35 ng*hr/ml |
| Expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Astellas | 97.04 ng*hr/ml |
| Expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Dr. Reddys | 110.63 ng*hr/ml |
| Expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Mylan | 96.83 ng*hr/ml |
| Expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Panacea | 100.58 ng*hr/ml |
| Expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Sandoz | 98.68 ng*hr/ml |
| Non-expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Panacea | 89.38 ng*hr/ml |
| Non-expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Accord | 92.37 ng*hr/ml |
| Non-expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Mylan | 85.53 ng*hr/ml |
| Non-expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Astellas | 84.16 ng*hr/ml |
| Non-expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Sandoz | 87.60 ng*hr/ml |
| Non-expressors | Compare AUC 0-12hr of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Dr. Reddys | 83.96 ng*hr/ml |
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [107.04, 125.22]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [95.91, 112.12]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [92.3, 107.89]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 and Cmax parameters90% CI: [95.83, 112.11]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 and parameters90% CI: [94.03, 110]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [103.26, 120.7]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [107.27, 125.49]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [103.27, 120.81]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [105.3, 123.08]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [96.08, 112.4]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [92.5, 108.21]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [94.28, 110.29]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [89.05, 104.09]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [90.72, 106.12]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [94.27, 110.19]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [100.42, 119.25]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [91.28, 109.03]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [92.99, 111.06]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [97.17, 116.06]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [95.25, 113.75]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [100.66, 120.24]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [98.82, 118.02]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [94.56, 112.94]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [96.48, 115.23]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [89.82, 107.28]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [85.96, 102.65]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [87.69, 104.74]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [87.56, 104.58]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [89.34, 107.71]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed AUC 0-12 parameters90% CI: [93.36, 111.51]
Primary
Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients
Report the geometric mean and 95% confidence interval for Cmax (ng/ml) for each formulation in expressor and non expressor transplant recipients
Time frame: Whole blood samples were collected immediately prior to dosing, at 1, 1.5, 1.75, 2, 2.5, 3 and 4 hours following dosing. Subjects were then instructed to performed fingersticks using dried blood spot cards at 8 and 12 hours post dose.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Mylan | 17.76 ng/ml |
| Expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Astellas | 15.31 ng/ml |
| Expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Panacea | 16.67 ng/ml |
| Expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Dr. Reddys | 15.94 ng/ml |
| Expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Sandoz | 14.40 ng/ml |
| Expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Accord | 21.72 ng/ml |
| Non-expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Sandoz | 12.75 ng/ml |
| Non-expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Astellas | 13.34 ng/ml |
| Non-expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Dr. Reddys | 13.58 ng/ml |
| Non-expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Mylan | 15.15 ng/ml |
| Non-expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Panacea | 13.23 ng/ml |
| Non-expressors | Compare Cmax of Each Tacrolimus Formulation in Expressor and Non Expressor Transplant Recipients | Accord | 15.07 ng/ml |
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [88.06, 111.64]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [91.15, 115.55]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [125.73, 160.16]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [92.33, 117.45]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [102.87, 130.87]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [96.51, 122.94]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [83.33, 106.16]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [120.82, 153.7]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [108.37, 138.04]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [115.43, 147.04]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [133.77, 170.18]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [79.52, 101.3]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [84.71, 107.9]
90% CI: [98.1, 124.96]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [94.44, 120.15]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [109.3, 139.23]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [102.68, 130.62]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [100.32, 127.2]
90% CI: [90.37, 114.57]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [100.82, 127.83]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [84.89, 107.61]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [98.59, 125]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [88.38, 112.04]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [101.18, 128.28]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [104.96, 133.08]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [79.61, 100.93]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [94.55, 119.88]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [110.68, 128.92]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [105.48, 133.74]
Comparison: Analysis of variance (PROC MIXED) was performed on log transformed Cmax parameters90% CI: [92.13, 116.81]
Secondary
To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects
Conduct safety lab testing specific to transplanted organ function and clinical assessments for adverse events.
Time frame: Assessed at baseline and weekly for 6 weeks at each pharmacokinetic profile
Population: Participants in the PK population with available data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Total Other Adverse Events (not including Serious) | 22 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Eye Disorder | 2 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Gastrointestinal | 4 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Ear and labyrinth | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Cardiac | 1 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Blood and Lymphatic system | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Nervous system | 2 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Renal and urinary | 1 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Metabolism and Nutrition | 2 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Vascular | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Psychiatric | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Skin and subcutaneous tissue | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Endocrine | 1 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Allergies | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Infections and infestations | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Reproductive system and breast disorders | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | All cause mortality | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Musculoskeletal and connective tissue | 1 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | General disorders and administrative site conditions | 4 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Serious Adverse Events | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Respiratory, thoracic, and mediastinal | 0 Participants |
| Expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Investigations | 4 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Vascular | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Serious Adverse Events | 0 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Eye Disorder | 0 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Endocrine | 0 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | General disorders and administrative site conditions | 3 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Metabolism and Nutrition | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Total Other Adverse Events (not including Serious) | 14 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Nervous system | 0 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Blood and Lymphatic system | 0 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Allergies | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Cardiac | 0 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Ear and labyrinth | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Gastrointestinal | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Respiratory, thoracic, and mediastinal | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Musculoskeletal and connective tissue | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Reproductive system and breast disorders | 0 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | All cause mortality | 0 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Infections and infestations | 0 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Skin and subcutaneous tissue | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Psychiatric | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Investigations | 1 Participants |
| Non-expressors | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Renal and urinary | 1 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Skin and subcutaneous tissue | 0 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | All cause mortality | 0 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Renal and urinary | 5 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Musculoskeletal and connective tissue | 1 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Infections and infestations | 0 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Cardiac | 1 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Investigations | 1 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Reproductive system and breast disorders | 0 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Blood and Lymphatic system | 1 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Endocrine | 0 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Ear and labyrinth | 0 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Total Other Adverse Events (not including Serious) | 20 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Eye Disorder | 1 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Gastrointestinal | 2 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Allergies | 0 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Nervous system | 2 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Vascular | 2 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | General disorders and administrative site conditions | 3 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Serious Adverse Events | 0 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Respiratory, thoracic, and mediastinal | 0 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Metabolism and Nutrition | 1 Participants |
| Dr. Reddys | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Psychiatric | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Cardiac | 1 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Total Other Adverse Events (not including Serious) | 22 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Ear and labyrinth | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Metabolism and Nutrition | 2 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Allergies | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Gastrointestinal | 2 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | General disorders and administrative site conditions | 7 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Respiratory, thoracic, and mediastinal | 2 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Endocrine | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Reproductive system and breast disorders | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Investigations | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Infections and infestations | 1 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Serious Adverse Events | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Skin and subcutaneous tissue | 1 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | All cause mortality | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Psychiatric | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Eye Disorder | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Nervous system | 4 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Musculoskeletal and connective tissue | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Renal and urinary | 1 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Blood and Lymphatic system | 0 Participants |
| Mylan | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Vascular | 1 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Metabolism and Nutrition | 4 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Eye Disorder | 0 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Renal and urinary | 1 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Respiratory, thoracic, and mediastinal | 1 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Vascular | 1 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Psychiatric | 0 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | All cause mortality | 0 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Blood and Lymphatic system | 0 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Gastrointestinal | 2 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Ear and labyrinth | 0 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Nervous system | 4 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Reproductive system and breast disorders | 0 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Investigations | 2 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Endocrine | 0 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Musculoskeletal and connective tissue | 2 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Infections and infestations | 1 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Serious Adverse Events | 0 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Total Other Adverse Events (not including Serious) | 23 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Allergies | 0 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | General disorders and administrative site conditions | 3 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Cardiac | 2 Participants |
| Panacea | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Skin and subcutaneous tissue | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | General disorders and administrative site conditions | 2 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | All cause mortality | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Serious Adverse Events | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Total Other Adverse Events (not including Serious) | 13 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Nervous system | 1 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Blood and Lymphatic system | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Cardiac | 1 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Metabolism and Nutrition | 2 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Gastrointestinal | 2 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Respiratory, thoracic, and mediastinal | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Musculoskeletal and connective tissue | 1 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Reproductive system and breast disorders | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Infections and infestations | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Skin and subcutaneous tissue | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Psychiatric | 1 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Vascular | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Investigations | 1 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Renal and urinary | 1 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Allergies | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Eye Disorder | 1 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Endocrine | 0 Participants |
| Sandoz | To Compare the Safety and Efficacy of Each Tacrolimus Formulation in Stable Transplant Subjects | Ear and labyrinth | 0 Participants |