A Phase II Open Label Multicenter Extension Study in Stable Liver Transplant Patients To Assess the Pharmacokinetic Profile, Safety, and Tolerability of Once-Daily Extended Release MeltDose® Tacrolimus Tablets (LCP-Tacro™) in Patients after Six Months of Therapy.
W. Kenneth Washburn, Rita R. Alloway, Devin E. Eckhoff, Lewis W. Teperman. University of Texas Health Science Center at San Antonio, TX; University of Cincinnati and The Christ Hospital, Cincinnati, OH; University of Alabama at Birmingham, AL; New York University Medical Center, New York, NY
Once-daily (qd) tablets (LCP-Tacro™; Veloxis Pharmaceuticals) is an extended release MeltDose® formulation of tacrolimus. Enhanced pharmacokinetics (PK), optimized dosing, and noninferior efficacy have been demonstrated for LCP-Tacro vs. TAC twice-daily (bid) capsules (Prograf®; AstellasPharma). This study evaluated long-term safety and tolerability in stable liver transplant recipients converted to LCP-Tacro tablets qd from Prograf capsules bid.
This open-label extension study included stable liver transplant patients (n=49) who successfully completed the core study (two-week PK study) and were maintained on LCP-Tacro for an additional 50 weeks at a dose determined by the standard of care in each center. The recommended whole blood trough level was 5-15 ng/mL. A 24-hour PK assessment was performed at week 26 ± 1.
The study population had a median age of 52 years and was 49% male and mostly white (81.6%). Forty-three patients completed the study and six withdraw: three experienced AE (high creatinine, headache and metastatic hepatocellular carcinoma), one did not comply with the protocol, one withdrew consent, and one moved out of the area. One mild acute rejection was reported and resolved, and there were no deaths or graft losses. The mean (SD) number of AEs by each patient was 2.6 (1.8).
At day 14 and week 26 there was a statistically significant correlation between AUCτ and Cmin. The PK profile of LCP-Tacro at day 14 was similar to the PK after six months of therapy.
|Pharmacokinetic Parameters (mean ± SD)||Day 14||Week 26|
|LCP-Tacro Dose (mg/day)||4.4 ± 2.01||4.6 ± 2.37|
|AUC (0-24 hr) (ng X hr/mL)||200.24 ± 56.29||186.94 ± 66.45|
|Peak systemic exposure (ng/mL)||12.87 ± 4.13||12.41 ± 4.48|
|Trough C24 TAC level (ng/mL)||6.48 ± 2.15||5.91 ± 2.58|
|Median Tmax (hr)||6.01||4.99|
|Correlation Coefficient between AUC and C24||0.914||0.922|