Conversion From Brand to Generic Tacrolimus in High Risk Transplant Recipients

NCT02014103 | Completed Phase 4 Results

• 2 other identifiers: 13-223-SOL-00102FDA
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

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.

Conditions

Complication of Transplant

Keywords

bioequivalence; tacrolimus; transplant; CYP3A5 expressors/non expressors

Outcome Measures

Primary Outcomes (2)

• 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

  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.

• 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

  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.

Secondary Outcomes (1)

• 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

Study Arms (6)

Sequence 1

ACTIVE COMPARATOR

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.

Drug: Prograf; Drug: Tacrolimus, Sandoz; Drug: Tacrolimus, Reddy Laboratory; Drug: Tacrolimus, Mylan; Drug: Tacrolimus, Accord; Drug: Tacrolimus, Pancea Biotech Limited

Sequence 2

ACTIVE COMPARATOR

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.

Drug: Prograf; Drug: Tacrolimus, Sandoz; Drug: Tacrolimus, Reddy Laboratory; Drug: Tacrolimus, Mylan; Drug: Tacrolimus, Accord; Drug: Tacrolimus, Pancea Biotech Limited

Sequence 3

ACTIVE COMPARATOR

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.

Drug: Prograf; Drug: Tacrolimus, Sandoz; Drug: Tacrolimus, Reddy Laboratory; Drug: Tacrolimus, Mylan; Drug: Tacrolimus, Accord; Drug: Tacrolimus, Pancea Biotech Limited

Sequence 4

ACTIVE COMPARATOR

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.

Drug: Prograf; Drug: Tacrolimus, Sandoz; Drug: Tacrolimus, Reddy Laboratory; Drug: Tacrolimus, Mylan; Drug: Tacrolimus, Accord; Drug: Tacrolimus, Pancea Biotech Limited

Sequence 5

ACTIVE COMPARATOR

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.

Drug: Prograf; Drug: Tacrolimus, Sandoz; Drug: Tacrolimus, Reddy Laboratory; Drug: Tacrolimus, Mylan; Drug: Tacrolimus, Accord; Drug: Tacrolimus, Pancea Biotech Limited

Sequence 6

ACTIVE COMPARATOR

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.

Drug: Prograf; Drug: Tacrolimus, Sandoz; Drug: Tacrolimus, Reddy Laboratory; Drug: Tacrolimus, Mylan; Drug: Tacrolimus, Accord; Drug: Tacrolimus, Pancea Biotech Limited

Interventions

Prograf DRUG

Administration of each formulation will be determined by sequence.

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Tacrolimus, Sandoz DRUG

Administration of each formulation will be determined by sequence.

Also known as: Sandoz tacrolimus

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Tacrolimus, Reddy Laboratory DRUG

Administration of each formulation will be determined by sequence.

Also known as: Reddy's Laboratory tacrolimus

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Tacrolimus, Mylan DRUG

Administration of each formulation will be determined by sequence.

Also known as: Mylan tacrolimus

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Tacrolimus, Accord DRUG

Administration of each formulation will be determined by sequence.

Also known as: Accord Healthcare tacrolimus

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Tacrolimus, Pancea Biotech Limited DRUG

Administration of each formulation will be determined by sequence.

Also known as: Panacea Biotech Limited tacrolimus

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• 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.
• Subject who has received a primary or secondary transplant.
• 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.
• BMI less than or equal to 40.

You may not qualify if:

• Evidence of any acute rejection
• Subjects who require dialysis within 6 months prior to study entry
• Recipients of multiple organ transplants
• 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.
• HepC positive subjects with liver biopsy proven recurrent disease considered relevant by physician oversight.
• Subjects with any severe medical condition requiring acute or chronic treatment that in the investigator's opinion would interfere with study participation
• 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.
• GFR ≤ 35 ml/min measured as estimated using the MDRD4 formula
• Subjects with AST, ALT, total bilirubin ≥ 3 X ULN or other evidence of severe liver disease
• 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)
• Subjects with clinically significant infections, requiring therapy, which, in the investigator's opinion, would interfere with the objectives of the study
• Other mental or physical conditions which in the investigator's opinion, are considered clinically significant
• Presence of intractable immunosuppressant complications or side effects resulting in dose adjustment of tacrolimus
• 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.
• An anticipated change in the immunosuppressive regimen during subject participation other than that required by the protocol

Sponsors & Collaborators

• University of Cincinnati: lead
• University of Colorado, Denver: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (1)

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Rita Alloway
• Organization: University of Cincinnati

rita.alloway@uc.edu

513.558.1568

Study Officials

• Rita R Alloway, PharmD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Professor

Study Record Dates

• First Submitted: October 21, 2013
• First Posted: December 18, 2013
• Study Start: March 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: October 15, 2024
• Results First Posted: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)