Clinical trial NCT02882113: Influence of CYP3A5 Polymorphism on Liver Function Abnormality and the Trough Level Change After Conversion
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Liver Dysfunction
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2016-08-29
Enrollment: 60
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: liver function abnormality rate
timeFrame: 24 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Kwang-Woong Lee, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.