NCT01889758

Brief Summary

The study is designed to compare the steady-state pharmacokinetics of Prograf (Brand) and the two most disparate generic formulations (Generic Hi and Generic Lo) in a fully replicated, 3-way cross-over study in stable kidney (n=36) and liver transplant (n=36) subjects.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jun 2013

Typical duration for phase_4

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2013

Completed
20 days until next milestone

First Submitted

Initial submission to the registry

June 21, 2013

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 28, 2013

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

February 22, 2016

Status Verified

February 1, 2016

Enrollment Period

2.6 years

First QC Date

June 21, 2013

Last Update Submit

February 19, 2016

Conditions

Kidney Transplant RecipientsLiver Transplant Recipients

Keywords

bioequivalencetacrolimuskidneylivertransplant

Outcome Measures

Primary Outcomes (3)

  • Comparison of bioequivalence between brand name prograf to generic Hi tacrolimus in all participants

    Ratio of C0, C12, AUC0-12h and Cmax and apply confidence interval (CI) testing at steady state of Prograf to generic Hi in stable kidney and liver transplant subjects

    Day 7, 14, 21, 28, 35, 42

  • Comparison of bioequivalence between brand name prograf to generic Lo tacrolimus in all participants

    Ratio of C0, C12, AUC0-12h and Cmax and apply confidence interval (CI) testing at steady state of Prograf to Generic Lo in stable kidney and liver transplant subjects.

    Day 7, 14, 21, 28, 35, 42

  • Comparison of bioequivalence between generic Hi tacrolimus to generic Lo tacrolimus in all participants

    Ratio of C0, C12, AUC0-12h and Cmax and apply confidence interval (CI) testing at steady state of Generic Hi to Generic Lo in stable kidney and liver transplant subjects.

    Day 7, 14, 21, 28, 35, 42

Secondary Outcomes (5)

  • Comparing the bioavailability of each tacrolimus formulations in stable kidney and liver transplant subjects using the dose-normalized C0, C12, AUC0-12h and Cmax data

    Day 7, 14, 21, 28, 35, 42

  • Evaluating intra-patient variability of tacrolimus pharmacokinetics of each formulation by comparing C0, C12, AUC0-12h, and Cmax

    Day 7, 14, 21, 28, 35, 42

  • Evaluating and comparing the pharmacokinetics of tacrolimus metabolites in terms of C0, C12, AUC0-12h, Cmax and intra-individual variability

    Day 7, 14, 21, 28, 35, 42

  • Comparing the safety of Prograf, Generic Hi and Generic Lo in stable kidney and liver transplant subjects

    Day 7, 14, 21, 28, 35, 42

  • Comparing the efficacy of Prograf, Generic Hi and Generic Lo in stable kidney and liver transplant subjects

    Day 7, 14, 21, 28, 35, 42

Study Arms (3)

Sequence 1

ACTIVE COMPARATOR

Tacrolimus Hi for 1 week with full PK on Day 7, then tacrolimus Lo for 1 week with full PK on Day 14, then Prograf for 1 week with full PK on Day 21, then tacrolimus Hi with full PK on Day 28, then Prograf for 1 week with full PK on Day 35, and then tacrolimus Lo for 1 week with full PK on Day 42

Drug: PrografDrug: Tacrolimus

Sequence 2

ACTIVE COMPARATOR

Tacrolimus Lo for 1 week with full PK on Day 7, then Prograf for 1 week with full PK on Day 14, then tacrolimus Hi for 1 week with full PK on Day 21, then tacrolimus Lo with full PK on Day 28, then tacrolimus Hi for 1 week with full PK on Day 35, and then Prograf for 1 week with full PK on Day 42

Drug: PrografDrug: Tacrolimus

Sequence 3

ACTIVE COMPARATOR

Prograf for 1 week with full PK on Day 7, then tacrolimus Hi for 1 week with full PK on Day 14, then tacrolimus Lo for 1 week with full PK on Day 21, then Prograf with full PK on Day 28, then tacrolimus Lo for 1 week with full PK on Day 35, and then tacrolimus Hi for 1 week with full PK on Day 42

Drug: PrografDrug: Tacrolimus

Interventions

PrografDRUG

Brand: Prograf Capsules, 1.0mg Tacrolimus capsules containing white to off white powder equivalent to 1.0 mg of anhydrous tacrolimus are hard gelatin capsules with white opaque body and ivory capsules.

Also known as: Brand
Sequence 1Sequence 2Sequence 3
TacrolimusDRUG

Generic Hi: Generic tacrolimus Capsules, 1.0mg. Manufacturer to be determined (Aim 1).

Also known as: Generic tacrolimus hi
Sequence 1Sequence 2Sequence 3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥18 years old, male or female
  • Able to participate and willing to give written informed consent and to comply with the study visits and restrictions.
  • Subject who has received a primary or secondary kidney or liver 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 greater than or equal to 19 but less than or equal to 40.
  • Ability to perform daily finger sticks to provide blood sample

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.
  • Hep C 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 aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin ≥ 3 X upper limit of normal (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
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

The Christ Hospital

Cincinnati, Ohio, 45267, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Related Publications (1)

  • Alloway RR, Vinks AA, Fukuda T, Mizuno T, King EC, Zou Y, Jiang W, Woodle ES, Tremblay S, Klawitter J, Klawitter J, Christians U. Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial. PLoS Med. 2017 Nov 14;14(11):e1002428. doi: 10.1371/journal.pmed.1002428. eCollection 2017 Nov.

    PMID: 29135993DERIVED

MeSH Terms

Interventions

Tacrolimuslepirudin

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic Chemicals

Study Officials

  • Rita R Alloway, PharmD, FCCP

    University of Cincinnati

    PRINCIPAL INVESTIGATOR

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 of Medicine

Study Record Dates

First Submitted

June 21, 2013

First Posted

June 28, 2013

Study Start

June 1, 2013

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

February 22, 2016

Record last verified: 2016-02

Locations

US(2)