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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01666951

Enrollment

Registered

2012-08-16

Start date

2012-11-30

Completion date

2013-05-31

Last updated

2015-07-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Renal Failure

Brief summary

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.

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.

Interventions

DRUGLCP-Tacro tablets

Tacrolimus

DRUGPrograf

Tacrolimus

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Pharmacokinetics (AUC) of LCP-Tacro Compared to Prograf After Kidney Transplantation	1 days	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.
Pharmacokinetics (Cmax and C24) of LCP-Tacro Compared to Prograf After Kidney Transplantation	1 days	The pharmacokinetic parameter (Cmax and C24) was evaluated on Day 1 in adult de novo kidney recipients.
Pharmacokinetics (Tmax) of LCP-Tacro Compared to Prograf After Kidney Transplantation	1 days	The pharmacokinetic parameter (Tmax) was evaluated on Day 1 in adult de novo kidney recipients.
Pharmacokinetics (Fluctuation) of LCP-Tacro Compared to Prograf After Kidney Transplantation	14 days	The pharmacokinetic parameter (Fluctuation) was evaluated on Day 14 in adult de novo kidney recipients.

Other

Measure	Time frame	Description
Daytime, Nighttime and Overnight Systolic Blood Pressure (SBP) on Day 14.	14 days	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.
Evaluation of the Short-term Efficacy of LCP-Tacro After the Start of Dosing.	30 days	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.
Daytime, Nighttime Overnight Systolic Blood Pressure (SBP) on Day 28.	28 days	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.
Ratio of Nighttime to Daytime Systolic Blood Pressure (SBP) on Day 14.	14 days	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.
Ratio of Nighttime to Daytime Systolic Blood Pressure (SBP) on Day 28.	28 days	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
LCP-Tacro LCP-Tacro Tablets, once daily (Veloxis Pharmaceuticals A/S, Horsholm, DK) LCP-Tacro tablets: Tacrolimus	17
Prograf Prograf Capsules, twice daily (Astellas Pharma US, Deerfield, IL) Prograf: Tacrolimus	17
Total	34

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Not dosed	1	1

Baseline characteristics

Characteristic	LCP-Tacro	Prograf	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	1 Participants	2 Participants
Age, Categorical Between 18 and 65 years	16 Participants	16 Participants	32 Participants
Age, Continuous	51.5 years STANDARD_DEVIATION 13.92	46.4 years STANDARD_DEVIATION 11.49	49.0 years STANDARD_DEVIATION 12.84
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	4 Participants	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants	13 Participants	29 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Black or African American	5 Participants	5 Participants	10 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	10 Participants	12 Participants	22 Participants
Region of Enrollment United States	17 participants	17 participants	34 participants
Sex: Female, Male Female	3 Participants	8 Participants	11 Participants
Sex: Female, Male Male	14 Participants	9 Participants	23 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	17 / 17	17 / 17
serious Total, serious adverse events	5 / 17	5 / 17

Outcome results

Primary

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.

Time frame: 1 days