Safety and Efficacy of LCP-Tacro™ Once Daily in Stable Renal Transplant Patients Converted From Prograf® Twice Daily

• Sponsor: Veloxis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00817206
• Collaborator: PPD (Industry)
• Enrollment: 326
• Location: 1
• Arms: 2
• Duration (Months): 26
• Patients Per Site Per Month: 12.5

Study Details

Study Description

Brief Summary

This is 2-armed parallel group, prospective, randomized, open-label, multicenter Phase 3 controlled trial to establish the efficacy and safety of conversion from maintenance immunosuppressive therapy with Prograf® capsules (tacrolimus, Astellas Pharma US, Inc., Deerfield, IL) twice daily to maintenance immunotherapy with LCP Tacro™ tablets (tacrolimus, LifeCycle Pharma A/S, Hoersholm, Denmark) once daily for the prevention of acute allograft rejection in stable adult kidney transplant patients. Patients on a stable dose of Prograf® will be randomly assigned to be converted from Prograf® twice daily to LCP Tacro™ once daily or to remain on maintenance therapy with Prograf® twice daily. Patients entering the study will be treated with assigned study drug and followed for one year for patient survival and the incidence of graft rejection or graft loss.

Condition or Disease	Intervention/Treatment	Phase
Renal Failure	Drug: LCP-Tacro; Drug: Prograf	Phase 3

Detailed Description

This is 2-armed parallel group, prospective, randomized, open-label, multicenter Phase 3 controlled trial to establish the efficacy and safety of conversion from maintenance immunosuppressive therapy with Prograf capsules (tacrolimus, Astellas Pharma US, Inc., Deerfield, IL) twice daily to maintenance immunotherapy with LCP-Tacro tablets (tacrolimus, LifeCycle Pharma A/S, Horsholm, Denmark) once daily for the prevention of acute allograft rejection in stable adult make and female kidney transplant patients. Recipients of kidney transplant 3 months to 5 years before Screening and on a stable dose of Prograf will be randomly assigned to be converted from Prograf twice daily to LCP-Tacro once daily or to remain on maintenance therapy with Prograf twice daily. There will be 11 study visits in the Treatment period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 326 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ph3, Open Label, Multi-Ctr, Pros, Rand Study -Efficacy and Safety, Conversion Prograf® Capsules BID to LCPTacro Tablets QD, for Prevent of Acute Allograft Rejection in Stable Kidney Transplant pt.
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LCP-Tacro LCP-Tacro tablets™, once daily (LifeCycle Pharma A/S, Hoersholm DK)	Drug: LCP-Tacro; LCP-Tacro tablets will be administered orally QD, at the same time in the morning to maintain trough levels at 5-15 ng/ML. Subsequent doses will be adjusted according to whole blood tacrolimus trough levels. LCP-Tarco (tacrolimus) tablets provided in 0.5 mg, 1 mg, 2 mg, and 5 mg tablets.; Other Names: tacrolimus tacrolimus modified release
Active Comparator: Prograf (tacrolimus) Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)	Drug: Prograf; Oral prograf doses will be given BID (in the morning and evening), to maintain trough levels of 5- 15 ng/mL. Prograf capsules (tacrolimus) capsules, twice daily oral, provided in 0.5 mg, 1 mg, and 5 mg capsules.; Other Names: tacrolimus

Outcome Measures

Primary Outcome Measures

1. Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up. [12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women at least 18 years of age who are recipients of a kidney transplant between 3 months and 5 years before the screening date

• Patients taking oral Prograf® capsules twice daily, at least 2 mg total dose per day, as part of their maintenance immunosuppression therapy, with tacrolimus trough levels of 5 to 15 ng/mL

• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days before receiving study drug

Exclusion Criteria:

• Recipients of any transplanted organ other than kidney

• Recipients of a bone marrow transplant

• Patients with an eGFR (MDRD7) < 30 mL/min at Screening

• Patients with a spot protein:creatinine ratio > 0.5

• Patients with a WBC count ≤ 2.8 ´ 109/L unless the WBC count has been stable for at least 2 weeks and the absolute neutrophil count is > 1.0 ´ 109 /L

• Patients unable to swallow study medication

• Patients incapable of understanding the purposes and risks of the study, who cannot give written informed consent and who are unwilling or unable to comply with the study protocol requirements

• Pregnant or nursing women

• Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception

• Patients who were treated with any other investigational agent within 3 months before Screening

• Patients who have taken sirolimus or everolimus within 3 months before Screening

• Patients on concurrent immunosuppression with MMF (CellCept) or MPS delayed-release tablets (Myfortic) who have not been on stable doses for at least 4 weeks before Screening

• Patients withdrawn from corticosteroids less than 30 days before Screening

• Patients with an episode of acute rejection requiring antibody therapy within 3 months before Screening

• Patients treated for acute rejection within 30 days before Screening

• Patients who are hepatitis C virus (HCV) negative who have received an HCV positive (HCV RNA by polymerase chain reaction or HCV antibody) donor kidney

• Patients seropositive for human immunodeficiency virus

• Patients with a current malignancy or a history of malignancy (within the past 5 years), except basal or nonmetastatic squamous cell carcinoma of the skin that has been treated successfully

• Patients with uncontrolled concomitant infection, a systemic infection requiring treatment, or any other unstable medical condition that could interfere with the study objectives

• Patients with severe diarrhea, vomiting, active peptic ulcer, or gastrointestinal disorder that may affect the absorption of tacrolimus

• Patients with any form of current substance abuse, psychiatric disorder, or a condition that, in the opinion of the investigator, may invalidate communication with the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Institute of Renal Research/ Sharp Memorial	San Diego	California	United States	92123

Sponsors and Collaborators

• Veloxis Pharmaceuticals
• PPD

Investigators

• Principal Investigator: Steven Steinberg, M.D., Claifornia Institute of Renal Research/Sharp Memorial

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Veloxis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00817206
• Other Study ID Numbers: LCP-Tacro 3001
• First Posted: Jan 6, 2009
• Last Update Posted: Sep 10, 2015
• Last Verified: Aug 1, 2015

• Keywords provided by Veloxis Pharmaceuticals: kidney transplantation; renal transplantation; maintenance immunosuppression; tacrolimus; Prevention of acute allograft rejection
• Additional relevant MeSH terms: Renal Insufficiency; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	LCP-Tacro	Prograf (Tacrolimus)
Arm/Group Description	LCP-Tacro tablets™, once daily (LifeCycle Pharma A/S, Hoersholm DK) LCP-Tacro: LCP-Tacro tablets will be administered orally QD, at the same time in the morning to maintain trough levels at 5-15 ng/ML. Subsequent doses will be adjusted according to whole blood tacrolimus trough levels. LCP-Tarco (tacrolimus) tablets provided in 0.5 mg, 1 mg, 2 mg, and 5 mg tablets.	Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL) Prograf: Oral prograf doses will be given BID (in the morning and evening), to maintain trough levels of 5- 15 ng/mL. Prograf capsules (tacrolimus) capsules, twice daily oral, provided in 0.5 mg, 1 mg, and 5 mg capsules.
Period Title: Overall Study
STARTED	163	163
COMPLETED	142	154
NOT COMPLETED	21	9

Baseline Characteristics

Arm/Group Title	LCP-Tacro	Prograf (Tacrolimus)	Total
Arm/Group Description	LCP-Tacro tablets™, once daily (LifeCycle Pharma A/S, Hoersholm DK) LCP-Tacro: LCP-Tacro tablets will be administered orally QD, at the same time in the morning to maintain trough levels at 5-15 ng/ML. Subsequent doses will be adjusted according to whole blood tacrolimus trough levels. LCP-Tarco (tacrolimus) tablets provided in 0.5 mg, 1 mg, 2 mg, and 5 mg tablets.	Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL) Prograf: Oral prograf doses will be given BID (in the morning and evening), to maintain trough levels of 5- 15 ng/mL. Prograf capsules (tacrolimus) capsules, twice daily oral, provided in 0.5 mg, 1 mg, and 5 mg capsules.	Total of all reporting groups
Overall Participants	163	163	326
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	146 89.6%	137 84%	283 86.8%
>=65 years	17 10.4%	26 16%	43 13.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.4 (11.71)	50.2 (13.49)	50.3 (1.61)
Sex: Female, Male (Count of Participants)
Female	46 28.2%	61 37.4%	107 32.8%
Male	117 71.8%	102 62.6%	219 67.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	26 16%	29 17.8%	55 16.9%
Not Hispanic or Latino	137 84%	134 82.2%	271 83.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.6%	1 0.3%
Asian	3 1.8%	3 1.8%	6 1.8%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.6%	1 0.3%
Black or African American	36 22.1%	34 20.9%	70 21.5%
White	120 73.6%	117 71.8%	237 72.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 2.5%	7 4.3%	11 3.4%
Region of Enrollment (participants) [Number]
United States	122 74.8%	121 74.2%	243 74.5%
Europe	41 25.2%	42 25.8%	83 25.5%

Outcome Measures

1. Primary Outcome

Title	Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

One patient in each arm were randomized but not treated. Only treated patients (modified ITT population) is included in the primary outcome measure. One patient death is listed under the Prograf arm; this patient died during follow up and did completet the study.

Arm/Group Title	LCP-Tacro	Prograf (Tacrolimus)
Arm/Group Description	LCP-Tacro tablets™, once daily (LifeCycle Pharma A/S, Hoersholm DK) LCP-Tacro: LCP-Tacro tablets will be administered orally QD, at the same time in the morning to maintain trough levels at 5-15 ng/ML. Subsequent doses will be adjusted according to whole blood tacrolimus trough levels. LCP-Tarco (tacrolimus) tablets provided in 0.5 mg, 1 mg, 2 mg, and 5 mg tablets.	Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL) Prograf: Oral prograf doses will be given BID (in the morning and evening), to maintain trough levels of 5- 15 ng/mL. Prograf capsules (tacrolimus) capsules, twice daily oral, provided in 0.5 mg, 1 mg, and 5 mg capsules.
Measure Participants	162	162
Death	2 1.2%	1 0.6%
Graft Failure	0 0%	0 0%
BPAR	1 0.6%	4 2.5%
Loss to follow up	0 0%	1 0.6%

Adverse Events

Time Frame	SAEs were collected for 1 year for all patients receiving at least one dose of study drug (mITT population).
Arm/Group Title	LCP-Tacro		Prograf (Tacrolimus)
Arm/Group Description	LCP-Tacro tablets™, once daily (LifeCycle Pharma A/S, Hoersholm DK) LCP-Tacro: LCP-Tacro tablets will be administered orally QD, at the same time in the morning to maintain trough levels at 5-15 ng/ML. Subsequent doses will be adjusted according to whole blood tacrolimus trough levels. LCP-Tarco (tacrolimus) tablets provided in 0.5 mg, 1 mg, 2 mg, and 5 mg tablets.		Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL) Prograf: Oral prograf doses will be given BID (in the morning and evening), to maintain trough levels of 5- 15 ng/mL. Prograf capsules (tacrolimus) capsules, twice daily oral, provided in 0.5 mg, 1 mg, and 5 mg capsules.
All Cause Mortality
	LCP-Tacro		Prograf (Tacrolimus)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LCP-Tacro		Prograf (Tacrolimus)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/162 (22.2%)		26/162 (16%)
Blood and lymphatic system disorders
Pancytopenia	1/162 (0.6%)	1	0/162 (0%)	0
Splenomegaly	1/162 (0.6%)	1	0/162 (0%)	0
Cardiac disorders
Acute myocardial infarction	1/162 (0.6%)	1	0/162 (0%)	0
Angina pectoris	2/162 (1.2%)	2	0/162 (0%)	0
Atrial fibrilation	0/162 (0%)	0	1/162 (0.6%)	1
Cardiac arrest	2/162 (1.2%)	2	0/162 (0%)	0
Myocardial ischaemia	0/162 (0%)	0	1/162 (0.6%)	1
Gastrointestinal disorders
Abdominal pain	1/162 (0.6%)	1	0/162 (0%)	0
Diarrhoea	2/162 (1.2%)	2	0/162 (0%)	0
Gastritis	0/162 (0%)	0	1/162 (0.6%)	1
Intestinal obstruction	1/162 (0.6%)	1	0/162 (0%)	0
Vomitting	1/162 (0.6%)	2	0/162 (0%)	0
Hepatobiliary disorders
Bile duct stenosis	0/162 (0%)	0	1/162 (0.6%)	1
Immune system disorders
Kidney transplant rejection	0/162 (0%)	0	1/162 (0.6%)	1
Infections and infestations
Bronchopulmonary aspergillosis	0/162 (0%)	0	1/162 (0.6%)	1
Cellulitits	2/162 (1.2%)	2	0/162 (0%)	0
Cytomegalovirus infection	1/162 (0.6%)	1	0/162 (0%)	0
Diverticulitis	0/162 (0%)	0	2/162 (1.2%)	2
Emphysematous pyelonephritis	1/162 (0.6%)	1	0/162 (0%)	0
Epstein-Barr virus infection	1/162 (0.6%)	1	0/162 (0%)	0
Escherichia urinary tract infection	0/162 (0%)	0	1/162 (0.6%)	2
Gastroenteritis	1/162 (0.6%)	1	2/162 (1.2%)	2
Gastroenteritis viral	0/162 (0%)	0	1/162 (0.6%)	1
Osteomyelitis	2/162 (1.2%)	3	0/162 (0%)	0
Pneumococcal infection	0/162 (0%)	0	1/162 (0.6%)	1
Pneumocystis jiroveci pneumonia	0/162 (0%)	0	1/162 (0.6%)	1
Pneumonia	1/162 (0.6%)	1	2/162 (1.2%)	2
Polyomavirus-associated nephropathy	1/162 (0.6%)	1	0/162 (0%)	0
Pyelonephritis	1/162 (0.6%)	1	0/162 (0%)	0
Urinary tract infection	3/162 (1.9%)	3	4/162 (2.5%)	4
Urosepsis	0/162 (0%)	0	1/162 (0.6%)	1
Viral Pericarditis	0/162 (0%)	0	1/162 (0.6%)	1
Vulval cellulitis	1/162 (0.6%)	1	0/162 (0%)	0
Injury, poisoning and procedural complications
Arterial injury	1/162 (0.6%)	1	0/162 (0%)	0
Drug toxicity	1/162 (0.6%)	1	0/162 (0%)	0
Femoral neck fracture	1/162 (0.6%)	1	0/162 (0%)	0
Incisional hernia	1/162 (0.6%)	1	0/162 (0%)	0
Muscle pain	0/162 (0%)	0	1/162 (0.6%)	1
Investigations
Blood creatinine increased	1/162 (0.6%)	1	2/162 (1.2%)	2
Epstein-Barr virus test positive	1/162 (0.6%)	1	0/162 (0%)	0
Metabolism and nutrition disorders
Diabetis mellitus	1/162 (0.6%)	1	0/162 (0%)	0
Diabetic ketoacidosis	1/162 (0.6%)	1	0/162 (0%)	0
Fluid overload	0/162 (0%)	0	1/162 (0.6%)	1
Hypoglycaemia	1/162 (0.6%)	1	0/162 (0%)	0
Hypophosphataemia	1/162 (0.6%)	1	0/162 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/162 (0%)	0	1/162 (0.6%)	1
Hepatic neoplasm	1/162 (0.6%)	1	0/162 (0%)	0
Renal cancer	2/162 (1.2%)	2	0/162 (0%)	0
Renal cancer recurrent	0/162 (0%)	0	1/162 (0.6%)	1
Renal cell carcinoma recurrent	0/162 (0%)	0	1/162 (0.6%)	1
Sqaumous cell carcinoma	1/162 (0.6%)	1	0/162 (0%)	0
Vulval cancer	1/162 (0.6%)	1	0/162 (0%)	0
Nervous system disorders
Brain stem haemorrhage	1/162 (0.6%)	1	0/162 (0%)	0
Cerebrovascular accident	1/162 (0.6%)	1	0/162 (0%)	0
Syncope	0/162 (0%)	0	1/162 (0.6%)	1
Psychiatric disorders
Depression	0/162 (0%)	0	1/162 (0.6%)	2
Renal and urinary disorders
Nephrolithiasis	0/162 (0%)	0	1/162 (0.6%)	1
Renal failure acute	0/162 (0%)	0	1/162 (0.6%)	2
Ureteric obstruction	1/162 (0.6%)	1	0/162 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/162 (0.6%)	1	0/162 (0%)	0
Pneumothorax spontaneous tension	1/162 (0.6%)	1	0/162 (0%)	0
Respiratory distress	0/162 (0%)	0	1/162 (0.6%)	1
Respiratory failure	0/162 (0%)	0	1/162 (0.6%)	1
Skin and subcutaneous tissue disorders
Dermatitis contact	0/162 (0%)	0	1/162 (0.6%)	1
Vascular disorders
Arterial disorder	0/162 (0%)	0	1/162 (0.6%)	1
Deep vein thrombosis	1/162 (0.6%)	1	1/162 (0.6%)	1
Hypertension	0/162 (0%)	0	1/162 (0.6%)	1
Hypertensive crisis	1/162 (0.6%)	1	0/162 (0%)	0
Peripheral ischaemia	1/162 (0.6%)	1	0/162 (0%)	0
Other (Not Including Serious) Adverse Events
	LCP-Tacro		Prograf (Tacrolimus)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	135/162 (83.3%)		133/162 (82.1%)
Gastrointestinal disorders
Diarrhoea	22/162 (13.6%)	31	15/162 (9.3%)	17
Nausea	10/162 (6.2%)	13	6/162 (3.7%)	6
General disorders
Oedema Peripheral	11/162 (6.8%)	12	10/162 (6.2%)	11
Infections and infestations
Nasopharyngitis	15/162 (9.3%)	16	18/162 (11.1%)	24
Urinary tract infection	14/162 (8.6%)	19	22/162 (13.6%)	39
Upper respiratory tract infection	12/162 (7.4%)	13	14/162 (8.6%)	16
Investigations
Blood creatinine increased	20/162 (12.3%)	20	14/162 (8.6%)	16
Musculoskeletal and connective tissue disorders
Pain in extremity	7/162 (4.3%)	10	9/162 (5.6%)	11
Nervous system disorders
Headache	15/162 (9.3%)	18	11/162 (6.8%)	12
Dizziness	9/162 (5.6%)	10	5/162 (3.1%)	5
Respiratory, thoracic and mediastinal disorders
Cough	9/162 (5.6%)	9	7/162 (4.3%)	8
Vascular disorders
Hypertension	7/162 (4.3%)	8	10/162 (6.2%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.