Renal Failure
Conditions
Keywords
kidney transplantation, renal transplantation, maintenance immunosuppression, tacrolimus, Prevention of acute allograft rejection
Brief summary
This is 2-armed parallel group, prospective, randomized, open-label, multicenter Phase 3 controlled trial to establish the efficacy and safety of conversion from maintenance immunosuppressive therapy with Prograf® capsules (tacrolimus, Astellas Pharma US, Inc., Deerfield, IL) twice daily to maintenance immunotherapy with LCP Tacro™ tablets (tacrolimus, LifeCycle Pharma A/S, Hoersholm, Denmark) once daily for the prevention of acute allograft rejection in stable adult kidney transplant patients. Patients on a stable dose of Prograf® will be randomly assigned to be converted from Prograf® twice daily to LCP Tacro™ once daily or to remain on maintenance therapy with Prograf® twice daily. Patients entering the study will be treated with assigned study drug and followed for one year for patient survival and the incidence of graft rejection or graft loss.
Detailed description
This is 2-armed parallel group, prospective, randomized, open-label, multicenter Phase 3 controlled trial to establish the efficacy and safety of conversion from maintenance immunosuppressive therapy with Prograf capsules (tacrolimus, Astellas Pharma US, Inc., Deerfield, IL) twice daily to maintenance immunotherapy with LCP-Tacro tablets (tacrolimus, LifeCycle Pharma A/S, Horsholm, Denmark) once daily for the prevention of acute allograft rejection in stable adult make and female kidney transplant patients. Recipients of kidney transplant 3 months to 5 years before Screening and on a stable dose of Prograf will be randomly assigned to be converted from Prograf twice daily to LCP-Tacro once daily or to remain on maintenance therapy with Prograf twice daily. There will be 11 study visits in the Treatment period.
Interventions
DRUGLCP-Tacro
LCP-Tacro tablets will be administered orally QD, at the same time in the morning to maintain trough levels at 5-15 ng/ML. Subsequent doses will be adjusted according to whole blood tacrolimus trough levels. LCP-Tarco (tacrolimus) tablets provided in 0.5 mg, 1 mg, 2 mg, and 5 mg tablets.
DRUGPrograf
Oral prograf doses will be given BID (in the morning and evening), to maintain trough levels of 5- 15 ng/mL. Prograf capsules (tacrolimus) capsules, twice daily oral, provided in 0.5 mg, 1 mg, and 5 mg capsules.
Sponsors
PPD Development, LP
Veloxis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women at least 18 years of age who are recipients of a kidney transplant between 3 months and 5 years before the screening date * Patients taking oral Prograf® capsules twice daily, at least 2 mg total dose per day, as part of their maintenance immunosuppression therapy, with tacrolimus trough levels of 5 to 15 ng/mL * Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days before receiving study drug
Exclusion criteria
* Recipients of any transplanted organ other than kidney * Recipients of a bone marrow transplant * Patients with an eGFR (MDRD7) \< 30 mL/min at Screening * Patients with a spot protein:creatinine ratio \> 0.5 * Patients with a WBC count ≤ 2.8 ´ 109/L unless the WBC count has been stable for at least 2 weeks and the absolute neutrophil count is \> 1.0 ´ 109 /L * Patients unable to swallow study medication * Patients incapable of understanding the purposes and risks of the study, who cannot give written informed consent and who are unwilling or unable to comply with the study protocol requirements * Pregnant or nursing women * Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception * Patients who were treated with any other investigational agent within 3 months before Screening * Patients who have taken sirolimus or everolimus within 3 months before Screening * Patients on concurrent immunosuppression with MMF (CellCept) or MPS delayed-release tablets (Myfortic) who have not been on stable doses for at least 4 weeks before Screening * Patients withdrawn from corticosteroids less than 30 days before Screening * Patients with an episode of acute rejection requiring antibody therapy within 3 months before Screening * Patients treated for acute rejection within 30 days before Screening * Patients who are hepatitis C virus (HCV) negative who have received an HCV positive (HCV RNA by polymerase chain reaction or HCV antibody) donor kidney * Patients seropositive for human immunodeficiency virus * Patients with a current malignancy or a history of malignancy (within the past 5 years), except basal or nonmetastatic squamous cell carcinoma of the skin that has been treated successfully * Patients with uncontrolled concomitant infection, a systemic infection requiring treatment, or any other unstable medical condition that could interfere with the study objectives * Patients with severe diarrhea, vomiting, active peptic ulcer, or gastrointestinal disorder that may affect the absorption of tacrolimus * Patients with any form of current substance abuse, psychiatric disorder, or a condition that, in the opinion of the investigator, may invalidate communication with the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. | 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LCP-Tacro LCP-Tacro tablets™, once daily (LifeCycle Pharma A/S, Hoersholm DK)
LCP-Tacro: LCP-Tacro tablets will be administered orally QD, at the same time in the morning to maintain trough levels at 5-15 ng/ML. Subsequent doses will be adjusted according to whole blood tacrolimus trough levels. LCP-Tarco (tacrolimus) tablets provided in 0.5 mg, 1 mg, 2 mg, and 5 mg tablets. | 163 |
| Prograf (Tacrolimus) Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)
Prograf: Oral prograf doses will be given BID (in the morning and evening), to maintain trough levels of 5- 15 ng/mL. Prograf capsules (tacrolimus) capsules, twice daily oral, provided in 0.5 mg, 1 mg, and 5 mg capsules. | 163 |
| Total | 326 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 3 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | LCP-Tacro | Prograf (Tacrolimus) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 26 Participants | 43 Participants |
| Age, Categorical Between 18 and 65 years | 146 Participants | 137 Participants | 283 Participants |
| Age, Continuous | 50.4 years STANDARD_DEVIATION 11.71 | 50.2 years STANDARD_DEVIATION 13.49 | 50.3 years STANDARD_DEVIATION 1.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants | 29 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 137 Participants | 134 Participants | 271 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 34 Participants | 70 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 7 Participants | 11 Participants |
| Race (NIH/OMB) White | 120 Participants | 117 Participants | 237 Participants |
| Region of Enrollment Europe | 41 participants | 42 participants | 83 participants |
| Region of Enrollment United States | 122 participants | 121 participants | 243 participants |
| Sex: Female, Male Female | 46 Participants | 61 Participants | 107 Participants |
| Sex: Female, Male Male | 117 Participants | 102 Participants | 219 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 135 / 162 | 133 / 162 |
| serious Total, serious adverse events | 36 / 162 | 26 / 162 |
Outcome results
Primary
Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up.
Time frame: 12 months
Population: One patient in each arm were randomized but not treated. Only treated patients (modified ITT population) is included in the primary outcome measure.~One patient death is listed under the Prograf arm; this patient died during follow up and did completet the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCP-Tacro | Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. | Death | 2 participants |
| LCP-Tacro | Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. | Graft Failure | 0 participants |
| LCP-Tacro | Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. | BPAR | 1 participants |
| LCP-Tacro | Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. | Loss to follow up | 0 participants |
| Prograf (Tacrolimus) | Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. | Loss to follow up | 1 participants |
| Prograf (Tacrolimus) | Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. | Death | 1 participants |
| Prograf (Tacrolimus) | Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. | BPAR | 4 participants |
| Prograf (Tacrolimus) | Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. | Graft Failure | 0 participants |