Trial Outcomes & Findings for Pharmacokinetics of LCP-Tacro(TM) Once Daily And Prograf® Twice A Day in Adult De Novo Kidney Transplant Patients (NCT NCT00765661)

Last Updated: 2015-05-19

Results Overview

Comparison of the proportion of patients achieving sufficient tacrolimus whole blood trough levels (7 to 20 ng/mL) during the first 14 days post-transplantation

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

14 days

Results posted on

2015-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	Group A Randomized, parallel group, open-label, multi-center study in adult de novo kidney transplant patients to demonstrate the pharmacokinetics and safety of LCP-Tacro tablets in the first 2 weeks after kidney transplantation. Eligible patients were randomized (1:1 ratio) within 12 hours after transplantation (Day 0) to receive LCP-Tacro tablets orally once daily (QD) in the morning, with an interval of 24 +/-1 hours between doses, starting at 0.14 mg/kg (the starting daily dose for African-American patients was 0.17 mg/kg)	Group B Randomized, parallel-group, open-label, multi-center study in adult de novo kidney transplant patients to demonstrate the pharmacokinetics and safety of Prograf capsules in the first 2 weeks after kidney transplantation. Eligible patients were randomized (1:1 ratio) within 12 hours after transplantation (Day 0) to receive Prograf capsules in 2 equally divided doses, starting at 0.1 mg/kg every 12 hours (0.2 mg/kg total daily dose) as recommended in the U.S. Prescribing Information
Overall Study STARTED	32	31
Overall Study COMPLETED	32	31
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of LCP-Tacro(TM) Once Daily And Prograf® Twice A Day in Adult De Novo Kidney Transplant Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gorup A n=32 Participants LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK) tacrolimus (Tacro™): LCP - Tacro™ tablets, orally	Group B n=31 Participants Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL) Prograf®: Prograf® capsules, twice daily, orally	Total n=63 Participants Total of all reporting groups
Age, Continuous	49.3 years STANDARD_DEVIATION 12 • n=5 Participants	46.1 years STANDARD_DEVIATION 13.87 • n=7 Participants	47.7 years STANDARD_DEVIATION 12.94 • n=5 Participants
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	32 Participants n=5 Participants	31 Participants n=7 Participants	63 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	9 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	22 Participants n=7 Participants	33 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants	31 participants n=7 Participants	63 participants n=5 Participants

PRIMARY outcome

Timeframe: 14 days

Comparison of the proportion of patients achieving sufficient tacrolimus whole blood trough levels (7 to 20 ng/mL) during the first 14 days post-transplantation

Outcome measures

Outcome measures
Measure	Group A n=28 Participants LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK) tacrolimus (Tacro™)	Group B n=28 Participants Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)
Pharmacokinetics of LCP-Tacro™ Tablets in the First 14 Days After Transplantation in Adult de Novo Kidney Recipients.	78.57 percentage of patients	57.14 percentage of patients

SECONDARY outcome

Timeframe: 14 days

Population: The outcome measure is listed as arithmetic mean of the pharmacokinetic parameters for raw data (not dose corrected) for tacrolimus in the ITT population on Day 14.

To compare the pharmacokinetics (AUC, Cmax, C24/Cmin) on Days 1, 7 and 14 of LCP-Tacro with the pharmacokinetics of Prograf in adult de novo kidney transplant patients.

Outcome measures

Outcome measures
Measure	Group A n=28 Participants LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK) tacrolimus (Tacro™)	Group B n=28 Participants Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)
Comparative Pharmacokinetics Between LCP-Tacro and Prograf Within 14 Days After Kidney Transplantation. Cmax	28.21 ng/mL Standard Deviation 13.68	20.27 ng/mL Standard Deviation 6.49
Comparative Pharmacokinetics Between LCP-Tacro and Prograf Within 14 Days After Kidney Transplantation. Cmin	10.37 ng/mL Standard Deviation 4.24	8.12 ng/mL Standard Deviation 3.13

SECONDARY outcome

Timeframe: 14 days

Population: The outcome measure is listed as arithmetic mean of the pharmacokinetic parameters for raw data (not dose corrected) for tacrolimus in the ITT population on Day 14.

To compare the pharmacokinetics (AUC, Cmax, C24/Cmin) on Days 1, 7 and 14 of LCP-Tacro with the pharmacokinetics of Prograf in adult de novo kidney transplant patients.

Outcome measures

Outcome measures
Measure	Group A n=28 Participants LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK) tacrolimus (Tacro™)	Group B n=28 Participants Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)
Comparative Pharmacokinetics Between LCP-Tacro and Prograf Within 14 Days After Kidney Transplantation.	349.31 ng*hr/mL Standard Deviation 112.41	255.22 ng*hr/mL Standard Deviation 80.39

SECONDARY outcome

Timeframe: 12 months

Population: All patients receiving at least one dose of study drug was included in the safety evaluation.

To evaluate the efficacy and safety of LCP-Tacro compared to Prograf in the first 12 months after kidney transplantation. Efficacy was assessed by monitoring biopsy-proven acute rejection (BPAR) according to the Banff criteria, graft failure (defined by a patient starting dialysis for at least 30 days, nephrectomy, retransplantation, or death with a functioning graft), patient survival, and renal function based on serum creatinine and glomerular filtration rate (GFR), based on serum creatinine, serum urea nitrogen, and serum albumin.

Outcome measures

Outcome measures
Measure	Group A n=32 Participants LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK) tacrolimus (Tacro™)	Group B n=31 Participants Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)
Evaluation of Safety and Efficacy of LCP-Tacro Compared to Prograf in Adult de Novo Kidney Transplant Patients. BPAR	0 participants	0 participants
Evaluation of Safety and Efficacy of LCP-Tacro Compared to Prograf in Adult de Novo Kidney Transplant Patients. Graft Failure	0 participants	2 participants
Evaluation of Safety and Efficacy of LCP-Tacro Compared to Prograf in Adult de Novo Kidney Transplant Patients. Death	0 participants	0 participants

Adverse Events

Group A

Serious events: 15 serious events

Other events: 32 other events

Deaths: 0 deaths

Group B

Serious events: 17 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Christina Sylvest, Sr VP Global Clinical Development & Operations

Veloxis

Phone: 45 20553877

Email: [email protected]

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 PIs.
Publication restrictions are in place

Restriction type: OTHER

Measure	Group A n=32 participants at risk LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK) tacrolimus (Tacro™): LCP - Tacro™ tablets	Group B n=31 participants at risk Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL) Prograf®: Prograf® capsules, twice daily
Infections and infestations gastroenteritis	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Metabolism and nutrition disorders dehydration	6.2% 2/32 • Number of events 2 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 2 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Metabolism and nutrition disorders hyponatremia	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations cytomegalovirus infection	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations localized infection	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations urinary tract infection	6.2% 2/32 • Number of events 3 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Gastrointestinal disorders nausea	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Gastrointestinal disorders abdominal pain	6.2% 2/32 • Number of events 2 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Respiratory, thoracic and mediastinal disorders pulmonary oedema	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Renal and urinary disorders ureteric stenosis	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Renal and urinary disorders obstructive uropathy	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Renal and urinary disorders hydronephrosis	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Cardiac disorders Cardiac failure congestive	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations vulval cellulitis	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Nervous system disorders transient ischaemic attack	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Gastrointestinal disorders vomitting	3.1% 1/32 • Number of events 2 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations urosepsis	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	0.00% 0/31 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Renal and urinary disorders acute renal failure	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	6.5% 2/31 • Number of events 2 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Immune system disorders serum sickness	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Renal and urinary disorders haemturia	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Surgical and medical procedures wound drainage	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Hepatobiliary disorders bile duct stone	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations pneumonia	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Injury, poisoning and procedural complications renal lymphocele	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
General disorders pyrexia	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Injury, poisoning and procedural complications post procedural urine leak	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Injury, poisoning and procedural complications complications of transplanted kidney	3.1% 1/32 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	9.7% 3/31 • Number of events 3 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations sepsis	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations lymph node tuberculosis	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Gastrointestinal disorders oesphagitis	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Vascular disorders lymphocele	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Musculoskeletal and connective tissue disorders musculoskeletal chest pain	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations viral infection	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations staphylococcal infection	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations staphylococcal sepsis	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Injury, poisoning and procedural complications incisional hernia	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Blood and lymphatic system disorders anemia macrocytic	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Blood and lymphatic system disorders coagulophathy	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Investigations internal normalized ratio increase	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Renal and urinary disorders renal tubular necrosis	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Infections and infestations bronchopneumonia	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Musculoskeletal and connective tissue disorders osteoarthritis	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Blood and lymphatic system disorders anaemia	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Metabolism and nutrition disorders hyperkalaemia	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
General disorders drug intolerance	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.
Vascular disorders hypotension	0.00% 0/32 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.	3.2% 1/31 • Number of events 1 • Adverse events were collected from Day 1 and up to end of study for a total of 12 months.