Conditions: Complication of Transplant
Keywords: bioequivalence tacrolimus transplant CYP3A5 expressors/non expressors
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 71
Healthy volunteers: no

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.

Arms:
arm 1: Patients will be randomized to a sequence of administration of the various 6 tacrolimus formulations. Sequence 1: Formulation Sandoz, Panacea, Accord, Mylan, Dr. Reddy's, Astellas

Patients will be receiving the same tacrolimus dose identified at baseline for each formulation. arm 2: Patients will be randomized to a sequence of administration of the various 6 tacrolimus formulations. Sequence 2: Formulation Accord, Sandoz, Dr. Reddy's, Panacea, Astellas, Mylan

Patients will be receiving the same tacrolimus dose identified at baseline for each formulation. arm 3: Patients will be randomized to a sequence of administration of the various 6 tacrolimus formulations. Sequence 3: Formulation Dr. Reddys, Accord, Astellas, Sandoz, Mylan, Panacea

Patients will be receiving the same tacrolimus dose identified at baseline for each formulation. arm 4: Patients will be randomized to a sequence of administration of the various 6 tacrolimus formulations. Sequence 4: Formulation Astellas, Dr. Reddy's, Mylan, Accord, Panacea, Sandoz

Patients will be receiving the same tacrolimus dose identified at baseline for each formulation. arm 5: Patients will be randomized to a sequence of administration of the various 6 tacrolimus formulations. Sequence 5: Formulation Mylan, Astellas, Panacea, Dr. Reddy's, Sandoz, Accord

Patients will be receiving the same tacrolimus dose identified at baseline for each formulation. arm 6: Patients will be randomized to a sequence of administration of the various 6 tacrolimus formulations. Sequence 6: Formulation Panacea, Mylan, Sandoz, Astellas, Accord, Dr. Reddy's

Patients will be receiving the same tacrolimus dose identified at baseline for each formulation.

Interventions: intervention 1: Prograf intervention 2: Tacrolimus, Sandoz intervention 3: Tacrolimus, Reddy Laboratory intervention 4: Tacrolimus, Mylan intervention 5: Tacrolimus, Accord intervention 6: Tacrolimus, Pancea Biotech Limited
Intervention descriptions: intervention 1: Administration of each formulation will be determined by sequence. intervention 2: Administration of each formulation will be determined by sequence. intervention 3: Administration of each formulation will be determined by sequence. intervention 4: Administration of each formulation will be determined by sequence. intervention 5: Administration of each formulation will be determined by sequence. intervention 6: Administration of each formulation will be determined by sequence.

Protocol document: