Influence of CYP3A5 Polymorphism on Liver Function Abnormality and the Trough Level Change After Conversion

Influence of CYP3A5 Polymorphism on Liver Function Abnormality and the Trough Level Change After Conversion From Tacrolimus (Bid) to Advagraf® (qd) in Stable Liver Transplant Recipients

This study is a multicenter, single-arm, open-label, 24 weeks, and investigator-initiated clinical trial to assess the influence of CYP3A5 polymorphism on liver function abnormality and the trough level change after conversion to Advagraf® in liver transplant recipients.

Study Overview

• Status: Unknown
• Conditions: Liver Dysfunction
• Intervention / Treatment: Drug: Advagraf

Detailed Description

All subjects who are liver transplant recipients taking Tacrolimus bid and adaptable to be registered for the study will be classified by expressive or non-expressive CYP3A5 polymorphism genotype and Advagraf® will be administered same dose as Tacrolimus bid der day in 24 weeks.

All subjects should check whether being registered in the hospital based on CYP3A5 polymorphism genotype during screening visit. Registered subjects will visit seven times to the hospital during the study which includes screening visit and adverse reaction, acute rejection, and trough level will be tested during this period. Subjects who are additionally agreed for PK study will be hospitalized with the state of Tacrolimus bid therapy one day ago before taking IP. On the first day of hospitalization, his/her blood will be collected. At week 1 (plus seven days) after conversion to Advagraf®, his/her blood will be collected for PK analysis.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Sung-Eun Kim; Phone Number: +82-10-6361-7139; Email: loveu0322@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 19 years old and above.
• Patients who previously have received a liver transplant over the last six months and within last three years.
• Patients who are on Tacrolimus immunosuppressive therapy twice a day for at least two weeks.

• During Tacrolimus immunosuppressive therapy twice a day for at least two weeks, patients who have following conditions.

  • Patients who have normal liver function and renal function.
  • Patients who have been monitored without complication such as acute rejection.
• Patients willing to sign his/her consent.

Exclusion Criteria:

• Patients who have Tacrolimus trough level resulted as 2 ng/mg at the baseline.
• Patients who are on steroid therapy due to positive result of acute rejection test before the baseline.
• Patients who have received a transplant besides liver.
• Patients who are allergic to IP or macrolide compounds.
• Patients who are on cyclosporine, bosentan, or potassium sparing diuretic.
• Patients with genetic diseases such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
• Pregnant or lactating women.
• Patients not willing to adhere to study procedures/treatments.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Expressor; CYP3A5 expressor; containing CYP3A5*1 wild-type allele(*1/*1 type & *1/*3 type) intervention: Advagraf conversion	Drug: Advagraf; same dose as Tacrolimus bid der day in 24 weeks; Other Names: Tacrolimus
Active Comparator: Non-expressor; CYP3A5 non-expressor: without CYP3A5*1 allele( *3/*3 type) intervention: Advagraf conversion	Drug: Advagraf; same dose as Tacrolimus bid der day in 24 weeks; Other Names: Tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
liver function abnormality rate	24 Weeks

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Kwang-Woong Lee, Dr., Seoul National University Hospital

Publications and helpful links

General Publications

• Kim JM, Ryu JH, Lee KW, Hong SK, Yang K, Choi GS, Kim YA, Lee JY, Yi NJ, Kwon CHD, Chu CW, Suh KS, Joh JW. Effect of CYP3A5 on the Once-Daily Tacrolimus Conversion in Stable Liver Transplant Patients. J Clin Med. 2020 Sep 8;9(9):2897. doi: 10.3390/jcm9092897.

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: August 24, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (Estimate): August 29, 2016

Study Record Updates

• Last Update Posted (Estimate): August 31, 2016
• Last Update Submitted That Met QC Criteria: August 30, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: AKR-ADVLT-2014-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided