Multicenter, Prospective, Rand, PK Study of LCP-Tacro™ Compared to Prograf® Capsules in De Novo Adult Kidney Transplant

Ph 2 Double-blind, Double-dummy, Multicenter, Prospective, Rand Study of PK of LCP-Tacro™ Tablets Once Daily, Compared to Prograf® Caps, Twice Daily, for Prevention of Acute Allograft Rejection in De Novo Adult Kidney Transplant Recipients

The purpose of this study is to evaluate the pharmacokinetics of LCP-Tacro tablets administered once-daily compared to Prograf capsules administered twice-daily after kidney transplantation.

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Drug: LCP-Tacro tablets; Drug: Prograf

Detailed Description

This is a 2-arm , parallel group, prospective, double-blind, double-dummy, multicenter,clinical trial to evaluate the pharmacokinetics of LCP-Tacro tablets once daily in comparison to Prograf capsules twice-daily after kidney transplantation.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Clinical Investigative Site 000015
    • San Francisco, California, United States, 94115
      • Clinical Investigative Site 000012
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Clinical Investigative Site 00004
  • Florida
    • Tampa, Florida, United States, 33606
      • Clinical Investigative Site 000002
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
      • Clinical Investigative Site 000005
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Clinical Investigative Site 000009
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Clinical Investigative Site 000010
  • New York
    • Buffalo, New York, United States, 14215
      • Clinical Investigative Site 000011
    • New York, New York, United States, 10016
      • Clinical Investigative Site 00006
  • Ohio
    • Cleveland, Ohio, United States, 44095
      • Clinical Investigative Site 00008
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Clinical Investigative Site 00003
  • Texas
    • Dallas, Texas, United States, 75246
      • Clinical Investigative Site 000013
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Clinical Investigative Site 00001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Give written consent
• Male and female subjects between the ages of 18 and 70 years, inclusive
• Must be receiving primary or secondary renal allograft from a deceased donor or non- HLA identical living donor
• WOCBP must have a negative pregnancy test
• Must have negative cross-match test and be ABO-compatible
• Must be able to swallow tablets and capsules

Exclusion criteria

• Recipients of any previous nonrenal or concurrent transplant
• Have panel reactive antibody >50%
• Any condition that may affect study drug absorption BMI <18 kg/m2 or > 45 kg/m2
• History of alcohol abuse with less than 6 months of sobriety
• History of recreational drug abuse with less than 6 months of documented abstinence
• Screening 12-lead ECG demonstrating CS abnormalities (including QTc prolongation)
• WOCBP and are either pregnant, lactating, planning to become pregnant or with a positive serum or urine pregnancy test
• Subjects (male or female) with reproductive potential who are unwilling/unable to use a double-barrier method
• Oral temperature (prior to study drug dosing) of 38.0ºC or higher
• CS active infections (eg, those requiring hospitalization, or as judged by the Investigator)
• Known hereditary immunodeficiency
• Malignancies or with a history of malignancies (within the last 5 years) with the exception of local, noninvasive, fully excised cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical carcinoma in situ
• Expect to receive within 2 months after randomization, or have received within 3 months prior to screening, any of the following: sirolimus, everolimus, belatacept, or cyclophosphamide
• Any psychiatric or medical condition that, in the Investigator's opinion, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study
• Clinically symptomatic CHF or documented EJF of less than 45%
• Significant COPD, pulmonary restrictive disease or significant pulmonary hypertension
• Enrolled in another investigational drug or device study, or who are less than 30 days since discontinuing
• Laboratory variables that are abnormal (outside laboratory reference range) and CS
• Positive results of any of the following serological tests: human immunodeficiency virus (HIV)-1 antibody, hepatitis B virus (HBV) surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAb), and anti-hepatitis C virus (HCV) antibody (HCV Ab)
• Subjects who have had primary focal segmental glomerulosclerosis
• Donor parameters must not include any of the following known conditions:

Donor with positive serological test result for HIV-1, HBV or HCV Donor with history of malignant disease (current or historical) Cold ischemia time >30 hours Non-heart-beating donor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCP-Tacro; LCP-Tacro Tablets, once daily (Veloxis Pharmaceuticals A/S, Horsholm, DK)	Drug: LCP-Tacro tablets; Tacrolimus; Other Names: Prograf
Active Comparator: Prograf; Prograf Capsules, twice daily (Astellas Pharma US, Deerfield, IL)	Drug: Prograf; Tacrolimus; Other Names: Prograf Capsules twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (AUC) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (AUC) was evaluated on Day 1 in adult de novo kidney recipients. Samples were collected from 0 to 24 hours post dose.	1 days
Pharmacokinetics (AUC) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (AUC) was evaluated on Day 14 in adult de novo kidney recipients. Samples were collected from 0 to 24 hours post dose.	14 days
Pharmacokinetics (AUC) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (AUC) was evaluated on Day 28 in adult de novo kidney recipients. Samples were collected from 0 to 24 hours post dose.	28 days
Pharmacokinetics (Cmax and C24) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (Cmax and C24) was evaluated on Day 1 in adult de novo kidney recipients.	1 days
Pharmacokinetics (Cmax and C24) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (Cmax and C24) was evaluated on Day 14 in adult de novo kidney recipients.	14 days
Pharmacokinetics (Cmax and C24) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (Cmax and C24) was evaluated on Day 28 in adult de novo kidney recipients.	28 days
Pharmacokinetics (Tmax) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (Tmax) was evaluated on Day 1 in adult de novo kidney recipients.	1 days
Pharmacokinetics (Tmax) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (Tmax) was evaluated on Day 14 in adult de novo kidney recipients.	14 days
Pharmacokinetics (Tmax) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (Tmax) was evaluated on Day 28 in adult de novo kidney recipients.	28 days
Pharmacokinetics (Fluctuation) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (Fluctuation) was evaluated on Day 14 in adult de novo kidney recipients.	14 days
Pharmacokinetics (Fluctuation) of LCP-Tacro Compared to Prograf After Kidney Transplantation	The pharmacokinetic parameter (Fluctuation) was evaluated on Day 28 in adult de novo kidney recipients.	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daytime, Nighttime and Overnight Systolic Blood Pressure (SBP) on Day 14.	At selected sites, a 24-hour measurement of blood pressure will be performed to assess the variability (ei, "nighttime dipping") between the two Groups at Days 14.	14 days
Daytime, Nighttime Overnight Systolic Blood Pressure (SBP) on Day 28.	At selected sites, a 24-hour measurement of blood pressure will be performed to assess the variability (ei, "nighttime dipping") between the two Groups at Day 28.	28 days
Ratio of Nighttime to Daytime Systolic Blood Pressure (SBP) on Day 14.	At selected sites, a 24-hour measurement of blood pressure will be performed to assess the variability (ei, "nighttime dipping") between the two Groups at Days 14.	14 days
Ratio of Nighttime to Daytime Systolic Blood Pressure (SBP) on Day 28.	At selected sites, a 24-hour measurement of blood pressure will be performed to assess the variability (ei, "nighttime dipping") between the two Groups at Days 28.	28 days
Evaluation of the Short-term Efficacy of LCP-Tacro After the Start of Dosing.	The efficacy is measured by the number of treatment failures defined as all-cause mortality, Graft Failure, Biopsy Proven Acute Rejection (BPAR) and Lost to follow up.	30 days

Collaborators and Investigators

• Sponsor: Veloxis Pharmaceuticals
• Investigators: Study Director: William Polvino, MD, Veloxis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: August 14, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimate): August 16, 2012

Study Record Updates

• Last Update Posted (Estimate): July 7, 2015
• Last Update Submitted That Met QC Criteria: June 30, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: LCP-Tacro 2019