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

Phase 4

• Conditions: Liver Dysfunction
• Interventions: Drug: Advagraf

• Registration Number: NCT02882113
• Lead Sponsor: Seoul National University Hospital

Brief Summary

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.

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 Timeline

• Status Verified: 2016-06
• Study Start: 2016-07
• Study First Submitted: 2016-08-24
• Study First Submitted QC: 2016-08-26
• Study First Posted: 2016-08-29
• Last Update Submitted: 2016-08-30
• Last Update Posted: 2016-08-31
• Primary Completion: 2018-08
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non-expressor	Advagraf	CYP3A5 non-expressor: without CYP3A5\*1 allele( \*3/\*3 type) intervention: Advagraf conversion
Expressor	Advagraf	CYP3A5 expressor; containing CYP3A5\*1 wild-type allele(\*1/\*1 type \& \*1/\*3 type) intervention: Advagraf conversion

Primary Outcome Measures

Name	Time	Method
liver function abnormality rate	24 Weeks

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of