Pharmacokinetics of Generic to Brand Tacrolimus in Stable Renal Transplant Patients

NCT01256294 | Completed Phase 4 Results

• 1 other identifier: CERL080AUS90
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 2

Brief Summary

The study is designed to compare the pharmacokinetics of generic tacrolimus (Sandoz) to branded tacrolimus (Prograf) in stable renal transplant patients.

Conditions

Renal Transplant

Keywords

Renal transplant; kidney transplant; immunosuppressive therapy; anti-rejection medication; pharmacokinetics; tacrolimus

Outcome Measures

Primary Outcomes (2)

• Dose-Normalized Area Under the Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) at Steady State

  Dose-normalized area under the concentration-time curve from time 0 to 12 hours (AUC0-12h) at steady state after 14 days of treatment with each study drug. Geometric mean and 95% confidence intervals were determined from an analysis of variance (ANOVA) model for the dose-normalized log transformed values with treatment, period and sequence as fixed factors and patients nested within sequences as a random factor.

  Days 14 and 28: Predose and at 0.5, 1, 1.5, 1.75, 2, 3, 4, 8 and 12 hours after dosing.

• Dose-normalized Maximum Plasma Drug Concentration (Cmax) at Steady State

  Maximum (peak) plasma drug concentration after drug administration at steady state (after 14 days of treatment with each study drug). Geometric mean and 95% confidence intervals were determined from an analysis of variance (ANOVA) model for the dose-normalized log transformed values with treatment, period and sequence as fixed factors and patients nested within sequences as a random factor.

  Days 14 and 28: Predose and at 0.5, 1, 1.5, 1.75, 2, 3, 4, 8 and 12 hours after dosing.

Secondary Outcomes (4)

• Intra-patient Variability of Tacrolimus Pharmacokinetic Parameters

  Days 7 and 14, and Days 21 and 28.

• Trough Plasma Drug Concentration (C0) at Steady State

  Days 14 and 28: predose

• Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

  28 Days

• Number of Participants With Reported Biopsy Proven Acute Rejection Episodes

  28 Days

Study Arms (2)

Sequence 1 - Branded Tacrolimus / Generic Tacrolimus

EXPERIMENTAL

In Period 1 (Days 1-14) participants received branded tacrolimus (Prograf) orally twice a day and in Period 2 (Days 15 - 28) participants received generic tacrolimus (Sandoz) orally twice a day. Participants received the same stable dosage of tacrolimus they had been taking prior to enrollment (on a milligram for milligram basis).

Drug: Generic Tacrolimus; Drug: Branded Tacrolimus

Sequence 2 - Generic Tacrolimus / Branded Tacrolimus

ACTIVE COMPARATOR

In Period 1 (Days 1 - 14) participants received generic tacrolimus (Sandoz) orally twice a day and in Period 2 (Days 15 - 28) participants received branded tacrolimus (Prograf) orally twice a day. Participants received the same stable dosage of tacrolimus they had been taking prior to enrollment (on a milligram for milligram basis).

Drug: Generic Tacrolimus; Drug: Branded Tacrolimus

Interventions

Generic Tacrolimus DRUG

Generic Sandoz tacrolimus supplied as capsules of 0.5 mg, 1 mg and 5 mg dose strengths.

Also known as: Sandoz

Sequence 1 - Branded Tacrolimus / Generic Tacrolimus; Sequence 2 - Generic Tacrolimus / Branded Tacrolimus

Branded Tacrolimus DRUG

Capsules supplied at dose strengths of 0.5 mg, 1 mg, and 5 mg.

Also known as: Prograf

Sequence 1 - Branded Tacrolimus / Generic Tacrolimus; Sequence 2 - Generic Tacrolimus / Branded Tacrolimus

Eligibility Criteria

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

You may qualify if:

• Able to participate and willing to give written informed consent and to comply with the study visits and restrictions.
• Patient who has received a primary or secondary kidney transplant
• Patient 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.
• Body mass index (BMI) greater than or equal to 19 but less than or equal to 35
• Patients who are taking tacrolimus (generic, Sandoz) or Prograf

You may not qualify if:

• Evidence of any acute rejection
• Patients who require dialysis within 6 months prior to study entry
• Recipients of antibodies blood group (ABO) incompatible allograft or positive crossmatch
• Recipients of multiple organ transplants
• Patients who have tested positive for hepatitis B surface antigen (HBsAG) or human immunodeficiency virus (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 was acceptable unless more recent tests were available.
• History of malignancy, treated or untreated, within the past 2 years with the exception of carcinoma in situ or excised basal cell carcinoma
• Glomerular filtration rate ≤35 ml/min measured by modification of diet in renal disease (MDRD4)
• No anticipated change in the immunosuppressive regimen during patient participation other than that required by the protocol
• Initiation of any medications that could interfere with tacrolimus blood levels, including over the counter medications, herbal supplements, grapefruit or grapefruit juice.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (\> 5 mIU/mL)
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are
• women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
• women whose partners have been sterilized by vasectomy or other means
• using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs); periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.
• Patients who are taking a generic tacrolimus product other than tacrolimus (generic, Sandoz).

Sponsors & Collaborators

• Novartis: lead
• Sandoz: collaborator

Study Sites (2)

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2010
• First Posted: December 8, 2010
• Study Start: October 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: June 21, 2012
• Results First Posted: June 21, 2012

Record last verified: 2012-05

Locations

US (2)