Immunosuppression
Conditions
Brief summary
Compare the difference in dose-normalized trough and total daily dose necessary to reach the steady state therapeutic goal after conversion from tacrolimus IR to Astagraf XL® in African American kidney transplant recipients.
Detailed description
The purpose of this study is to compare the difference in medication dosage and total daily dose necessary of Astagraf XL® in order to reach therapy goal, when taken with other medications that are routinely used for kidney transplantation, which may stop the development of a substance that can cause long-term damage to the transplanted kidney. African American kidney transplant patients aged 18 and above who are underwent a kidney transplant are eligible to participate. The duration of the study is 3 months.
Interventions
DRUGTacrolimus Extended Release Capsule
goal trough 5 - 12ng/mL
DRUGMycophenolate mofetil
≥500mg twice a day
DRUGPrednisone
goal dose 5mg daily
≥360mg twice a day
Sponsors
Astellas Pharma Inc
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years of age 2. Signed informed consent 3. African American race 4. History of a solitary renal transplant 5. Stable tacrolimus dose for at least 2 weeks prior to randomization
Exclusion criteria
1. A condition or disorder that, in the opinion of the investigator, may adversely affect the outcome of the study or the safety of the subject 2. Currently enrolled in an investigational drug trial 3. History of a non-renal organ transplant 4. History of acute cellular rejection within 1 month prior to randomization 5. An increase in serum creatinine by \> 20% in the 2 weeks prior to randomization 6. Maintenance immunosuppression that does not consist of tacrolimus IR given twice daily, mycophenolate mofetil \> 1000mg TDD or mycophenolate sodium \> 720mg TDD, and prednisone ≥ 5mg daily
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-normalized Trough | Baseline to 3 months post-conversion | Difference in dose-normalized trough at steady state before and after conversion from tacrolimus IR to Astagraf XL® |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight-Based Dose Requirement | Baseline to 3 months post conversion | Weight-based dose requirements to reach therapeutic goal pre- and post-conversion |
| Number of Days to Reach Therapeutic Trough Goal | Baseline to 3 months post conversion | Days to reach therapeutic goal after conversion |
| Total Daily Dose | Baseline to 3 months post conversion | Difference in Total Daily Dose necessary for steady state therapeutic goal |
| Dose Modifications | Baseline to 3 months post conversion | Number of dose modifications from baseline to 3 months post-conversion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Conversion Arm Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Conversion Arm |
|---|---|
| Age, Continuous | 52 years |
| BMI | 31.7 kg/m^2 STANDARD_DEVIATION 6.1 |
| Calculated Panel Reactive Antibodies (cPRA) | 50 percent |
| Cold Ischemic Time | 18.1 hours |
| Number of Days Since Transplant | 270 days |
| Number of participants on Hemodialysis Prior to Transplant | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 12 Participants |
| Warm Ischemic Time | 38.7 minutes STANDARD_DEVIATION 7.1 |
| Weight | 94.5 kilograms STANDARD_DEVIATION 23 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 19 / 25 |
| serious Total, serious adverse events | 1 / 25 |
Outcome results
Primary
Dose-normalized Trough
Difference in dose-normalized trough at steady state before and after conversion from tacrolimus IR to Astagraf XL®
Time frame: Baseline to 3 months post-conversion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conversion Arm | Dose-normalized Trough | Pre-Conversion Dose Trough | 0.59 ng/dL |
| Conversion Arm | Dose-normalized Trough | Post-Conversion Dose Trough | 0.44 ng/dL |
Secondary
Dose Modifications
Number of dose modifications from baseline to 3 months post-conversion.
Time frame: Baseline to 3 months post conversion
Population: 12 participants are homozygous, 10 are heterozygous, and 3 are non-expressors. This represents the 25 total subjects in the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conversion Arm | Dose Modifications | Homozygous CYP3A5 1 expressors | 1 number of dose modifications |
| Conversion Arm | Dose Modifications | Heterozygous CYP3A5 1 expressors | 2 number of dose modifications |
| Conversion Arm | Dose Modifications | CYP3A5 1 non expressers | 4 number of dose modifications |
Secondary
Number of Days to Reach Therapeutic Trough Goal
Days to reach therapeutic goal after conversion
Time frame: Baseline to 3 months post conversion
Population: Days to reach therapeutic goal was further separated by CYP3A5 1 expression.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conversion Arm | Number of Days to Reach Therapeutic Trough Goal | Homozygous CYP3A5 1 expressors | 15 number of days |
| Conversion Arm | Number of Days to Reach Therapeutic Trough Goal | Heterozygous CYP3A5 1 expressors | 10 number of days |
| Conversion Arm | Number of Days to Reach Therapeutic Trough Goal | CYP3A5 1 non-expressors | 15 number of days |
Secondary
Total Daily Dose
Difference in Total Daily Dose necessary for steady state therapeutic goal
Time frame: Baseline to 3 months post conversion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conversion Arm | Total Daily Dose | Pre-Conversion Tacrolimus Dose | 10 mg |
| Conversion Arm | Total Daily Dose | Post-Conversion Tacrolimus Dose | 15 mg |
Secondary
Weight-Based Dose Requirement
Weight-based dose requirements to reach therapeutic goal pre- and post-conversion
Time frame: Baseline to 3 months post conversion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conversion Arm | Weight-Based Dose Requirement | Pre-Conversion | 0.11 mg/kg |
| Conversion Arm | Weight-Based Dose Requirement | Post-Conversion | 0.16 mg/kg |