Trial Outcomes & Findings for Pharmacokinetics of LCP-Tacro in Stable Kidney Transplant Patients (NCT NCT00496483)
NCT ID: NCT00496483
Last Updated: 2015-07-23
Results Overview
Patients had a baseline trough level (C24) measured at day 7 before conversion to LCP-Tacro.
COMPLETED
PHASE2
60 participants
7 days
2015-07-23
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 7 to 12 ng/mL.
|
|---|---|
|
Overall Study
STARTED
|
60
|
|
Overall Study
Dosed
|
51
|
|
Overall Study
COMPLETED
|
48
|
|
Overall Study
NOT COMPLETED
|
12
|
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 7 to 12 ng/mL.
|
|---|---|
|
Overall Study
Not dosed
|
9
|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
Lack of Efficacy
|
1
|
Baseline Characteristics
Pharmacokinetics of LCP-Tacro in Stable Kidney Transplant Patients
Baseline characteristics by cohort
| Measure |
LCP-Tacro
n=60 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Age, Continuous
|
45.6 years
STANDARD_DEVIATION 12.08 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
60 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 7 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. 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 |
LCP-Tacro
n=47 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Evaluation of Steady State Tacrolimus Trough Levels (C24).
|
7.00 ng/mL
Standard Deviation 1.54
|
PRIMARY outcome
Timeframe: 7 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. 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.
Outcome measures
| Measure |
LCP-Tacro
n=47 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Evaluation of Steady State Tacrolimus Exposure (AUC 0-24).
|
218.82 ng*hr/mL
Standard Deviation 55.99
|
PRIMARY outcome
Timeframe: 21 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. Another patient discontinued before the Day 21 visit. 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 |
LCP-Tacro
n=46 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Evaluation of Steady State Tacrolimus Exposure Trough Levels (C24).
|
6.94 ng/mL
Standard Deviation 2.20
|
PRIMARY outcome
Timeframe: 21 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. Another patient discontinued before the Day 21 visit. 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).
Outcome measures
| Measure |
LCP-Tacro
n=46 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Evaluation of Steady State Tacrolimus Exposure (AUC 0-24).
|
218.03 ng*hr/mL
Standard Deviation 68.23
|
SECONDARY outcome
Timeframe: 21 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. Another patient discontinued before the Day 21 visit. The arithmetic mean and standard deviation is given.
Cmax and Cavg was measured at day 21 (Cmin was measured as part of the primary outcome).
Outcome measures
| Measure |
LCP-Tacro
n=46 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 21.
Cmax
|
13.94 ng/mL
Standard Deviation 5.84
|
|
Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 21.
Cavg
|
9.08 ng/mL
Standard Deviation 2.84
|
SECONDARY outcome
Timeframe: 21 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. Another patient discontinued before the Day 21 visit.
Tmax was measured at day 21 (Cmin was measured as part of the primary outcome).
Outcome measures
| Measure |
LCP-Tacro
n=46 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Tacrolimus Pharmacokinetics (Tmax) Was Measured at Day 21.
|
6.00 hour
Interval 1.5 to 16.0
|
SECONDARY outcome
Timeframe: 21 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. Another patient discontinued before the Day 21 visit. Arithmetic mean and standard deviation is given below.
Degree og fluctuation and degree of swing was measured at day 21 (Cmin was measured as part of the primary outcome).
Outcome measures
| Measure |
LCP-Tacro
n=46 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 21.
Fluctuation
|
77.04 percentage
Standard Deviation 50.59
|
|
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 21.
Swing
|
110.07 percentage
Standard Deviation 89.23
|
SECONDARY outcome
Timeframe: 7 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. The arithmetic mean and standard deviation is given.
Cmax and Cavg was measured at baseline day 7 (Cmin was measured as part of the primary outcome).
Outcome measures
| Measure |
LCP-Tacro
n=47 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 7.
Cmax
|
19.14 ng/mL
Standard Deviation 8.15
|
|
Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 7.
Cavg
|
9.12 ng/mL
Standard Deviation 2.33
|
SECONDARY outcome
Timeframe: 7 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. Another patient discontinued before the Day 21 visit.
Tmax was measured at baseline day 7 (Cmin was measured as part of the primary outcome).
Outcome measures
| Measure |
LCP-Tacro
n=46 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Tacrolimus Pharmacokinetics (Tmax) Was Measured at Day 7.
|
1.82 hour
Interval 0.5 to 24.0
|
SECONDARY outcome
Timeframe: 7 daysPopulation: 48 completed treatment with LCP-Tacro but one patient was excluded from the PP analysis due to inappropriate conversion rate. Arithmetic mean and standard deviation is given below.
Degree og fluctuation and degree of swing was measured as baseline at day 7 (Cmin was measured as part of the primary outcome).
Outcome measures
| Measure |
LCP-Tacro
n=47 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 7.
Fluctuation
|
127.41 percentage
Standard Deviation 57.28
|
|
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 7.
Swing
|
174.55 percentage
Standard Deviation 93.72
|
SECONDARY outcome
Timeframe: 52 daysPopulation: 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 |
LCP-Tacro
n=60 Participants
LCP-Tacro 1 mg, 2 mg and 5 mg tablets administered orally QD, dosing per conversion algorithm to maintain tacrolimus trough concentrations between 7 to 12 ng/mL.
|
|---|---|
|
Safety Evaluation
Graft failure
|
0 participants
|
|
Safety Evaluation
BPAR
|
0 participants
|
|
Safety Evaluation
Death
|
0 participants
|
Adverse Events
LCP-Tacro
Prograf
Serious adverse events
| Measure |
LCP-Tacro
n=51 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 7 to 12 ng/mL.
60 patients were enrolled into the study, but only 51 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 7 to 12 ng/mL.
60 patients were entrolled into the study and one withdrew consent right after screening. Therefore 59 patients are inlcuded in the ITT safety set.
|
|---|---|---|
|
Cardiac disorders
Angina Pectoris
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
General disorders
Pyrexia
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
Other adverse events
| Measure |
LCP-Tacro
n=51 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 7 to 12 ng/mL.
60 patients were enrolled into the study, but only 51 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 7 to 12 ng/mL.
60 patients were entrolled into the study and one withdrew consent right after screening. Therefore 59 patients are inlcuded in the ITT safety set.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Diabetes Mellitus
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/51
|
3.4%
2/59 • Number of events 2
|
|
Investigations
Urinary casts
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.0%
1/51 • Number of events 1
|
1.7%
1/59 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
2.0%
1/51 • Number of events 1
|
1.7%
1/59 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus hypersecretion
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
3.9%
2/51 • Number of events 2
|
0.00%
0/59
|
|
Cardiac disorders
Angina pectoris
|
3.9%
2/51 • Number of events 2
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Dsypnoea
|
3.9%
2/51 • Number of events 2
|
0.00%
0/59
|
|
General disorders
Chills
|
3.9%
2/51 • Number of events 2
|
0.00%
0/59
|
|
Nervous system disorders
Headache
|
5.9%
3/51 • Number of events 3
|
0.00%
0/59
|
|
Gastrointestinal disorders
Constipation
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Vascular disorders
Phlebitis
|
3.9%
2/51 • Number of events 2
|
0.00%
0/59
|
|
General disorders
Pain
|
2.0%
1/51 • Number of events 1
|
1.7%
1/59 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
General disorders
Application site irritation
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Eye disorders
Conjunctuvitis
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal pain
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
General disorders
Pyrexia
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Vascular disorders
Poor venous access
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Investigations
Heart rate increased
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
General disorders
Oedema peripheral
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Investigations
Cardiac murmur
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Leukocytosis
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Investigations
Blood pressure increased
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Investigations
Immunosuppressant drug level increased
|
0.00%
0/51
|
1.7%
1/59 • Number of events 1
|
|
Infections and infestations
Gatroenteritis
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
|
Vascular disorders
Hypertension
|
2.0%
1/51 • Number of events 1
|
0.00%
0/59
|
Additional Information
Christina Sylvest, Sr VP, Global Clinical Development and Operations
Veloxis A/S
Results disclosure agreements
- Principal investigator is a sponsor employee The 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 PI's.
- Publication restrictions are in place
Restriction type: OTHER