Trial Outcomes & Findings for Pharmacokinetics of LCP-Tacro in Stable Liver Transplant Patients (NCT NCT00608244)

NCT ID: NCT00608244

Last Updated: 2015-08-28

Results Overview

Patients had a baseline trough level (C24) measured at day 7 before conversion to LCP-Tacro.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 59 participants
• Primary outcome timeframe: 7 Days
• Results posted on: 2015-08-28

Participant Flow

Participant milestones

Measure	LCP-Tacro All Patients received Prograf for 7 days, then all patients were converted to once daily LCP-Tacro for 14 days. One dose adjustment up or down 25% was permitted on Day 15. On Day 22, patients were converted back to their original twice daily dose of Prograf for a safety follow-up period of 30 days. LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL.
Overall Study STARTED	59
Overall Study COMPLETED	57
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	LCP-Tacro All Patients received Prograf for 7 days, then all patients were converted to once daily LCP-Tacro for 14 days. One dose adjustment up or down 25% was permitted on Day 15. On Day 22, patients were converted back to their original twice daily dose of Prograf for a safety follow-up period of 30 days. LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL.
Overall Study Adverse Event	1
Overall Study Low trough levels	1

Baseline Characteristics

Pharmacokinetics of LCP-Tacro in Stable Liver Transplant Patients

Baseline characteristics by cohort

Measure	LCP-Tacro n=59 Participants Evaluation of steady state tacrolimus exposure (AUC0-24) and trough levels (C24) in stable liver transplant recipients converted from Prograf to LCP-Tacro in a 3-sequence study design and validate the dose conversion ratio determined in the Phase 1 program.
Age, Continuous	49.8 years STANDARD_DEVIATION 11.15 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	59 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	59 participants n=5 Participants

PRIMARY outcome

Timeframe: 7 Days

Population: The arithmetic mean and standard deviation is given.

Patients had a baseline trough level (C24) measured at day 7 before conversion to LCP-Tacro.

Outcome measures

Measure	Prograf n=57 Participants Prograf 0.5 mg, 1 mg and 5 mg capsules administered orally twice daily, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL.
Evaluation of Steady State Tacrolimus Trough Levels (C24).	6.72 ng/mL Standard Deviation 2.07

PRIMARY outcome

Timeframe: 7 Days

Population: The arithmetic mean and standard deviation is given.

Patients had a baseline AUC measured (0 to 24 hours) at day 7 before conversion to LCP-Tacro.

The following time points were used to obtain the PK curve for Prograf on day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 15, 16, 20 and 24 hours after the morning dose.

Outcome measures

Measure	Prograf n=57 Participants Prograf 0.5 mg, 1 mg and 5 mg capsules administered orally twice daily, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL.
Evaluation of Steady State Tacrolimus Exposure (AUC 0-24).	205.14 ng*hr/mL Standard Deviation 61.0

PRIMARY outcome

Timeframe: 21 Days

Population: 57 completed the study but one patient was excluded from the PP analysis due to low trough levels. The arithmetic mean and standard deviation is given.

Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, a trough level (C24) was measured.

Outcome measures

Measure	Prograf n=56 Participants Prograf 0.5 mg, 1 mg and 5 mg capsules administered orally twice daily, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL.
Evaluation of Steady State Tacrolimus Exposure Trough Levels (C24).	6.85 ng/mL Standard Deviation 2.63

PRIMARY outcome

Timeframe: 21 Days

Population: 57 completed the study but one patient was excluded from the PP analysis due to low trough levels. The arithmetic mean and standard deviation is given.

Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, AUC was measured (0 to 24 hours).

The following time points were used to obtain the PK curve for LCP-Tacro on day 21: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20 and 24 hours post-dose.

Outcome measures

Measure	Prograf n=56 Participants Prograf 0.5 mg, 1 mg and 5 mg capsules administered orally twice daily, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL.
Evaluation of Steady State Tacrolimus Exposure (AUC 0-24) on Day 21.	215.66 ng*hr/mL Standard Deviation 79.40

PRIMARY outcome

Timeframe: 52 days

Population: All enrolled patients are included in the safety population.

A combination of deaths, graft failure and biopsy proven acute rejections (BPAR) was used to evaluate the safety.

Outcome measures

Measure	Prograf n=59 Participants Prograf 0.5 mg, 1 mg and 5 mg capsules administered orally twice daily, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL.
Safety Evaluation Death	0 participants
Safety Evaluation Graft Failure	0 participants
Safety Evaluation BPAR	0 participants

Adverse Events

LCP-Tacro

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Prograf

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	LCP-Tacro n=59 participants at risk LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL. 59 patients were enrolled into the study and all 59 were dosed with LCP-Tacro.	Prograf n=59 participants at risk Prograf 0.5 mg, 1 mg and 5 mg capsules administered orally twice daily, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL. 59 patients were enrolled into the study and all 59 were dosed with Prograf. Adverse Events occurring during the follow up period (Days 22-51) have been counted in the Prograf treatment arm as patients were on Prograf during this period.
Cardiac disorders myocardial infarction	1.7% 1/59 • Number of events 1 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	0.00% 0/59 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.

Other adverse events

Measure	LCP-Tacro n=59 participants at risk LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL. 59 patients were enrolled into the study and all 59 were dosed with LCP-Tacro.	Prograf n=59 participants at risk Prograf 0.5 mg, 1 mg and 5 mg capsules administered orally twice daily, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 5 to 15 ng/mL. 59 patients were enrolled into the study and all 59 were dosed with Prograf. Adverse Events occurring during the follow up period (Days 22-51) have been counted in the Prograf treatment arm as patients were on Prograf during this period.
General disorders Fatigue	10.2% 6/59 • Number of events 8 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	3.4% 2/59 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.
Infections and infestations Upper respiratory infection	5.1% 3/59 • Number of events 3 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	3.4% 2/59 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.
Investigations Contusion	5.1% 3/59 • Number of events 3 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	0.00% 0/59 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.
General disorders Oedema peripheral	5.1% 3/59 • Number of events 3 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	0.00% 0/59 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.
Nervous system disorders Dizziness	5.1% 3/59 • Number of events 3 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	1.7% 1/59 • Number of events 1 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.
Nervous system disorders Tremor	5.1% 3/59 • Number of events 3 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	1.7% 1/59 • Number of events 1 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.
Investigations Liver function test abnormal	3.4% 2/59 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	1.7% 1/59 • Number of events 1 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.
Musculoskeletal and connective tissue disorders Muscle spasms	3.4% 2/59 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	0.00% 0/59 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.
Gastrointestinal disorders Nausea	3.4% 2/59 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	1.7% 1/59 • Number of events 1 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.
Nervous system disorders headache	3.4% 2/59 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.	0.00% 0/59 • Adverse events were collected from time of first dose of study drug and until the end of the follow up period at day 52.

Additional Information

Christina Sylvest

Veloxis Pharmaceuticals A/S

Phone: +45 20553877

Email: csy@veloxis.com

Results disclosure agreements

• Principal investigator is a sponsor employee This study is a multicenter collaborative investigation and the clinical trial results are to be published as a collaborative manuscript. Authorship will reflect varying levels of individual contribution to the study by the individual PIs.
• Publication restrictions are in place

Restriction type: OTHER