A Study to Evaluate the Effect of Advagraf Conversion From Prograf in Liver Transplant Subjects (Maple)

A Phase IV, Randomized, Open-Label, Comparative, Multi-Center Study to Assess the Safety and Efficacy of Advagraf® (Modified Release Tacrolimus, Once Daily) After Using Prograf® (Tacrolimus Twice Daily) in de Novo Liver Transplant Recipients

The objective of this study is to compare the efficacy and safety between a group that has been on Prograf twice daily therapy but converted to Advagraf once daily therapy and a group that maintained Prograf twice daily therapy.

Study Overview

• Status: Completed
• Conditions: de Novo Liver Transplant Subjects
• Intervention / Treatment: Drug: Prograf; Drug: Advagraf

Detailed Description

De novo Liver Transplant Recipients will be divided into two groups. Both groups will receive Prograf (Tacrolimus twice daily therapy), and at Month 1 (Week 4) after surgery, Prograf will be converted to Advagraf (modified release Tacrolimus, once daily) in one group, while Prograf therapy will be continued in other group.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A subject scheduled for liver transplantation from a living donor or brain dead
• In case of a woman of childbearing potential, a subject with a negative pregnancy test prior to enrollment and who consents to and would practice double contraception throughout the study (Pessary therapy, or rhythm method, or sexual abstinence, surgical sterilization, menopause or otherwise sterile; however, oral contraceptives are excluded.)
• A subject with terminal hepatic failure for which liver transplant is necessary
• A subject who understands and is completely aware of the study objective and risks and who submitted a written informed consent form on study participation

Exclusion Criteria:

• A subject who received multiple organ transplants or any previous organ transplant (including re-transplantation of the liver)
• A subject who had received auxiliary transplant or used the bioartificial liver (cellular system)
• A subject allergic or resistant to macrolide antibiotics or Tacrolimus
• A subject who was taking Cyclosporine and Bosentan (Tracleer) that may interact with Tacrolimus, or potassium-sparing diuretics known to possibly cause hyperkalemia (Spironolactone, Triamterene) at screening
• A subject who requires immunosuppressive treatment or systemic chemotherapy from before transplant. However, a subject who received immunosuppressive treatment for less than 1 month prior to transplant to treat underlying hepatic disorder may be enrolled in the study if treatment is discontinued at the time of transplant.
• A subject with malignancy or malignant tumor history within the past 5 years; however, a subject may be enrolled in this study in case of successfully cured for basal cell carcinoma or squamous cell carcinoma of the skin.
• A subject who suffers severe diarrhea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect Tacrolimus absorption (may be determined at the discretion of the investigator)
• A subject with any type of substance abuse, psychological disorder, or communication disorder at the discretion of the investigator
• A subject who is participating in another study or participated within 28 days of the study, or who had received IP or non-registered medication
• A subject who is pregnant or breastfeeding
• A subject (transplant recipient) and/or donor who are positive to HIV
• A subject who cannot comply with the protocol-planned routine visit schedule
• A subject who is not appropriate for study participation at the discretion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Advagraf conversion group; Oral	Drug: Prograf; oral; Other Names: Tacrolimus; Drug: Advagraf; oral; Other Names: modified release Tacrolimus
Active Comparator: Prograf maintenance group; Oral	Drug: Prograf; oral; Other Names: Tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of biopsy-confirmed acute rejection	Acute rejection incidence (%) = Number of subjects with at least one biopsy -confirmed acute rejection / Total number of subjects included in the relevant analysis set * 100	from Week 4 to Week 24 post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of biopsy-confirmed acute rejection		from Week 4 to Week 12 or Week 24
Severity of biopsy-confirmed acute rejection	Severity guideline is Banff criteria	from Week 4 to Week 12 and Week 24 after liver transplant
Subject survival rate and graft survival rate		from Week 4 to Week 12 and Week 24 after liver transplant
Safety assessed by the incidence of adverse events, vital signs, physical exam. and labo-tests		for 24 weeks after liver transplant

Collaborators and Investigators

• Sponsor: Astellas Pharma Korea, Inc.
• Investigators: Study Director: Medical Director, Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2013
• Primary Completion (Actual): January 3, 2017
• Study Completion (Actual): January 3, 2017

Study Registration Dates

• First Submitted: June 18, 2013
• First Submitted That Met QC Criteria: June 18, 2013
• First Posted (Estimated): June 20, 2013

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: immunosuppressant; FK506; tacrolimus
• Additional Relevant MeSH Terms: Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: ADV-LT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.