Clinical trial NCT00772148
Conditions: Liver Failure
Keywords: Liver Hepatic Transplantation Immunosuppression Tacrolimus Prograf
Sponsor: Veloxis Pharmaceuticals
Start date: 2008-10-01; Completion date: 2010-05-01
Enrollment: 58 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to demonstrate the pharmacokinetics (PK, measuring the amount of medication in blood samples) and safety of a new medicine, LCP-Tacro™ tablets, and Prograf® capsules, a drug commonly taken by transplant recipients to prevent the body from rejecting a transplanted kidney and liver. LCP-Tacro is a tablet containing the same active ingredient (tacrolimus) that is in Prograf capsules, but the tablet has been designed to release tacrolimus over an extended period so that it only has to be taken once daily. LCP-Tacro is an investigational drug.

This study will evaluate the levels of tacrolimus in the blood in the first two weeks after a liver transplant in patients randomly assigned (by chance, like flipping a coin) to take either LCP-Tacro™ tablets (tacrolimus) once daily or Prograf® capsules twice daily. In addition, patients will remain on study drug for 360 days in order to evaluate the relative safety of LCP-Tacro™ tablets compared to Prograf over a longer period of time.

Detailed description:
This was a randomized, parallel-group, open-label, multicenter study in adult de novo liver transplant patients to demonstrate the pharmacokinetics and safety of once-daily treatment of LCP-Tacro tablets and twice-daily Prograf capsules in the first 2 weeks after live transplantation. The study also compared the efficacy and safety of LCP-Tacro and Prograf over an additional 50 weeks after liver transplantation. Eligible patients were randomized (1:1 ratio) within 72 hours after transplantation (graft reperfusion) to receive either: 1) LCP-Tacr tablets orally once daily (QD) in the morning, with an interval of 24 +/- 1 hours between dosed, starting at 0.07 to 0.11 mg/kg (the starting daily dose for African-American patients was 0.09 to 0.13 mg/kg), or 2) Prograf capsules in 2 equally divided morning and evening doses, starting at 0.10 to 0.15 mg. Subsequent doses of study medications were to be adjusted by the investigator according to local practice to maintain a target whole blood tacrolimus trough level of 5 to 20 ng/mL thought Day 14. Twenty-four-hour pharmacokinetic assessments were performed on Days 1, 7 and 14; additionally whole blood tacrolimus trough levels for statistical analysis were measured on Days 2, 3, 4, 7, 10, 12, 12, 42, 90, 120, 180, 270, and 360. Physicians could also perform tacrolimus trough levels at other times at their discretion. On Day 360, the patients were placed on maintenance immunosuppressive regimen determined by their treating physician. Following completion of the third and final pharmacokinetic assessment on Day 14, patients entered the maintenance phase (Days 15 to 360) of study and remained on their assigned study medication until Day 360. Visits for safety assessments and tacrolimus trough levels during the maintenance phase were on Days 42, 90, 120, 180, 270 and 360.

Immunosuppressive therapy after the conclusion of the study was to be administered at the discretion of the patient's population.

Arms: arm 1: LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK) arm 2: Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)
Interventions: intervention 1: LCP -Tacro intervention 2: Prograf
Intervention descriptions: intervention 1: LCP-Tacro tablets will be administered orally once daily in the morning starting at 0.07 - 0.11 mg/kg. The starting dose for African-American patients will be 0.09 - 0.13 mg/kg. Subsequent doses of each study drug will be adjusted to maintain target whole blood tacrolimus trough levels of 5 - 20 ng/mL.

Other Names:Tacrolimus modified-release LCP-Tacro™ tablets (0.5 mg, 1 mg, 2 mg, 5 mg) intervention 2: Oral Prograf capsules will be administered starting at 0.10 - 0.15 mg/kg per day in two equally divided morning and evening doses. Subsequent doses of each study drug will be adjusted to maintain target whole blood tacrolimus trough levels of 5 - 20 ng/mL.

Other name: tacrolimus Prograf® capsules (0.5 mg, 1 mg, 5 mg)

Protocol documents: