Trial Outcomes & Findings for Pharmacokinetic Comparison Of All FK-506 Formulations (NCT NCT02339246)

Last Updated: 2016-01-18

Results Overview

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate T(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

32 participants

Primary outcome timeframe

8 days

Results posted on

2016-01-18

Participant Flow

32 patients were screened (enrolled) and 31 were randomized to treatment.

Participant milestones

Participant milestones
Measure	Envarsus XR Envarsus XR tablets once daily.	Astagraf XL Astagraf XL capsules once daily.	Prograf Prograf capsules twice daily.
First Intervention (7 Days) STARTED	0	0	31
First Intervention (7 Days) COMPLETED	0	0	31
First Intervention (7 Days) NOT COMPLETED	0	0	0
Second Intervention (7 Days) STARTED	16	15	0
Second Intervention (7 Days) COMPLETED	16	15	0
Second Intervention (7 Days) NOT COMPLETED	0	0	0
Third Period (7 Days) STARTED	15	16	0
Third Period (7 Days) COMPLETED	15	16	0
Third Period (7 Days) NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetic Comparison Of All FK-506 Formulations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prograf vs Envarsus XR vs Astagraf XL n=16 Participants Prograft capsules Twice daily Envarsus XR tablets once daily Astagraf XL capsules once daily Prograf vs Envarsus XR vs Astagraf XL: prograf vs Envarsus XR vs Astagraf XL	Prograf vs Astagraf XL vs Envarsus XR n=15 Participants Prograf capsules twice daily Astagraf XL capsules once daily Envarsus XR tablets once daily Prograf vs Astagraf XL vs Envarsus XR: Prograf vs Astagraf XL vs Envarsus XR	Total n=31 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	50.1 years STANDARD_DEVIATION 11.00 • n=5 Participants	46.3 years STANDARD_DEVIATION 13.30 • n=7 Participants	48.3 years STANDARD_DEVIATION 12.11 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	15 participants n=7 Participants	31 participants n=5 Participants

PRIMARY outcome

Timeframe: 8 days

Population: One patient in the Envarsus XR arm was excluded from the analysis due to non compliance.

Outcome measures

Outcome measures
Measure	Envarsus XR n=30 Participants Envarsus XR tablets once daily.	Astagraf XL n=30 Participants Astagraf XL capsules once daily.	Prograf n=30 Participants Prograf capsules twice daily.
Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf.	5.91 hour Interval 1.45 to 13.95	1.93 hour Interval 0.92 to 5.92	1.48 hour Interval 0.93 to 19.97

PRIMARY outcome

Timeframe: 8 days

Population: One patient in the Envarsus XR arm was excluded from the analysis due to non compliance.

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate C(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.

Outcome measures

Outcome measures
Measure	Envarsus XR n=30 Participants Envarsus XR tablets once daily.	Astagraf XL n=30 Participants Astagraf XL capsules once daily.	Prograf n=30 Participants Prograf capsules twice daily.
Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf.	13.88 ng/mL Standard Deviation 5.331	13.17 ng/mL Standard Deviation 12.49	14.54 ng/mL Standard Deviation 13.60

PRIMARY outcome

Timeframe: 8 days

Population: One patient in the Envarsus XR arm was excluded from the analysis due to non compliance.

Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate AUC(0-24). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24.

Outcome measures

Outcome measures
Measure	Envarsus XR n=30 Participants Envarsus XR tablets once daily.	Astagraf XL n=30 Participants Astagraf XL capsules once daily.	Prograf n=30 Participants Prograf capsules twice daily.
Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf.	213.41 hr*ng/mL Standard Deviation 83.095	165.02 hr*ng/mL Standard Deviation 48.910	176.52 hr*ng/mL Standard Deviation 50.799

Adverse Events

Envarsus XR

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Astagraf XR

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Prograf

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Envarsus XR n=31 participants at risk Envarsus XR tablets once daily.	Astagraf XR n=31 participants at risk Astagraf XR capsules once daily.	Prograf n=31 participants at risk Prograf capsules twice daily.
Gastrointestinal disorders Diarrhea	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	6.5% 2/31 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	3.2% 1/31 • Number of events 1 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.
Gastrointestinal disorders Vomiting	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	6.5% 2/31 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.
General disorders Fatigue	6.5% 2/31 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.
General disorders Oedema peripheral	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	9.7% 3/31 • Number of events 3 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.
Infections and infestations Nasopharyngitis	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	6.5% 2/31 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.
Nervous system disorders Headache	0.00% 0/31 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	3.2% 1/31 • Number of events 1 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.	6.5% 2/31 • Number of events 2 • Adverse events were collected from time of first dose of study drug and until last visit which was approximately 1 month.

Additional Information

Christina Sylvest

Veloxis Pharmaceuticals

Phone: +4520553877

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60