Trial Outcomes & Findings for A Pharmacokinetic Analysis of Tacrolimus ER Dosing in Obese Kidney Transplant Recipients (NCT NCT02444143)

Last Updated: 2018-11-07

Results Overview

Difference in tacrolimus exposure (area under the concentration-time curve from time 0 to 24 hours (AUC-0-24)) in obese patients who received an initial TAC -ER dose of 0.15 mg/kg using aBW versus IBW

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

20 participants

Primary outcome timeframe

Days 1-14

Results posted on

2018-11-07

Participant Flow

Participant milestones

Participant milestones
Measure	Ideal Body Weight- Tacrolimus Extended Release tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on Ideal Body Weight (IBW)	Adjusted Body Weight-Tacrolimus Extended Release tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on adjusted Body Weight (aBW)
Overall Study STARTED	10	10
Overall Study COMPLETED	10	9
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Pharmacokinetic Analysis of Tacrolimus ER Dosing in Obese Kidney Transplant Recipients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ideal Body Weight- Tacrolimus Extended Release n=10 Participants tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on Ideal Body Weight (IBW)	Adjusted Body Weight-Tacrolimus Extended Release n=10 Participants tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on adjusted Body Weight (aBW)	Total n=20 Participants Total of all reporting groups
Age, Continuous	60.3 years STANDARD_DEVIATION 8.6 • n=5 Participants	47.7 years STANDARD_DEVIATION 14.3 • n=7 Participants	54 years STANDARD_DEVIATION 11.45 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Body Mass Index greater than or equal to 30 on Post Operative Day 0	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Donor Type Deceased	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Donor Type Living-unrelated	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Donor Type Living-related	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Duration of Pre-transplant dialysis	45.8 days STANDARD_DEVIATION 36.6 • n=5 Participants	55.8 days STANDARD_DEVIATION 46.8 • n=7 Participants	50.8 days STANDARD_DEVIATION 41.7 • n=5 Participants
Cause of End Stage Renal Disease hypertension (HTN)	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Cause of End Stage Renal Disease diabetes mellitus (DM)	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Cause of End Stage Renal Disease DM + HTN	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Cause of End Stage Renal Disease Other	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Hospital stay in days	7 days n=5 Participants	6.5 days n=7 Participants	6.75 days n=5 Participants
Body Mass Index at Transplant	38.2 kg/m2 STANDARD_DEVIATION 5.2 • n=5 Participants	43.4 kg/m2 STANDARD_DEVIATION 6.8 • n=7 Participants	40.8 kg/m2 STANDARD_DEVIATION 6 • n=5 Participants
Weight at Transplant	116.8 kg STANDARD_DEVIATION 30.2 • n=5 Participants	136.4 kg STANDARD_DEVIATION 30.5 • n=7 Participants	126.6 kg STANDARD_DEVIATION 30.35 • n=5 Participants
Ideal Body Weight	68 kg STANDARD_DEVIATION 13.3 • n=5 Participants	71.5 kg STANDARD_DEVIATION 11.8 • n=7 Participants	69.75 kg STANDARD_DEVIATION 12.55 • n=5 Participants
Adjusted Body Weight	86.7 kg STANDARD_DEVIATION 19.5 • n=5 Participants	97.5 kg STANDARD_DEVIATION 17.9 • n=7 Participants	92.1 kg STANDARD_DEVIATION 18.7 • n=5 Participants

PRIMARY outcome

Timeframe: Days 1-14

Population: This study randomized de novo kidney transplant recipients who were at least 18 years of age and obese as evidenced by a BMI ≥ 30 on the day of transplantation.

Outcome measures

Outcome measures
Measure	Ideal Body Weight- Tacrolimus Extended Release n=10 Participants tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on Ideal Body Weight (IBW)	Adjusted Body Weight-Tacrolimus Extended Release n=10 Participants tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on adjusted Body Weight (aBW)
Difference in Tacrolimus Exposure (AUC-0-24)) in Obese Patients Who Received an Initial TAC -ER Dose of 0.15 mg/kg Using aBW Versus IBW day 1 AUC 0-24	115.2 ng•h/mL Standard Deviation 51.3	90.0 ng•h/mL Standard Deviation 51.2
Difference in Tacrolimus Exposure (AUC-0-24)) in Obese Patients Who Received an Initial TAC -ER Dose of 0.15 mg/kg Using aBW Versus IBW day 7 AUC 0-24	268.3 ng•h/mL Standard Deviation 59.9	269.3 ng•h/mL Standard Deviation 101.1
Difference in Tacrolimus Exposure (AUC-0-24)) in Obese Patients Who Received an Initial TAC -ER Dose of 0.15 mg/kg Using aBW Versus IBW day 14 AUC 0-24	355.0 ng•h/mL Standard Deviation 75.4	267.3 ng•h/mL Standard Deviation 101.3

SECONDARY outcome

Timeframe: Days 1 to 7

Difference in the time to a therapeutic tacrolimus trough level in the aBW group compared to the IBW group.

Outcome measures

Outcome measures
Measure	Ideal Body Weight- Tacrolimus Extended Release n=10 Participants tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on Ideal Body Weight (IBW)	Adjusted Body Weight-Tacrolimus Extended Release n=10 Participants tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on adjusted Body Weight (aBW)
Difference in Time to Therapeutic Level	4.9 days Standard Deviation 3.1	5.1 days Standard Deviation 4.0

Adverse Events

Ideal Body Weight- Tacrolimus Extended Release

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Adjusted Body Weight-Tacrolimus Extended Release

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Patricia West-Thielke

University of Illinois at Chicago

Phone: 312-996-5695

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ideal Body Weight- Tacrolimus Extended Release n=10 participants at risk tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on Ideal Body Weight (IBW)	Adjusted Body Weight-Tacrolimus Extended Release n=10 participants at risk tacrolimus extended release (Astagraf) 0.15 mg/kg/day based on adjusted Body Weight (aBW)
Cardiac disorders Edema	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Cardiac disorders Hypertension	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	0.00% 0/10 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Cardiac disorders Hypotension	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Endocrine disorders Hyperglycemia	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	0.00% 0/10 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Gastrointestinal disorders Gastroparesis	0.00% 0/10 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	30.0% 3/10 • Number of events 3 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Gastrointestinal disorders Vomiting	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Gastrointestinal disorders Diarrhea	40.0% 4/10 • Number of events 4 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	40.0% 4/10 • Number of events 4 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Gastrointestinal disorders Nausea	30.0% 3/10 • Number of events 3 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	30.0% 3/10 • Number of events 3 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Gastrointestinal disorders Constipation	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	0.00% 0/10 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Renal and urinary disorders Microalbuminuria	0.00% 0/10 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Renal and urinary disorders Hematuria	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Renal and urinary disorders Urinary retention	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Metabolism and nutrition disorders Hypophosphatemia	50.0% 5/10 • Number of events 5 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	50.0% 5/10 • Number of events 5 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Metabolism and nutrition disorders Hypomagnesemia	60.0% 6/10 • Number of events 6 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	60.0% 6/10 • Number of events 6 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Metabolism and nutrition disorders Hyperkalemia	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	60.0% 6/10 • Number of events 6 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Metabolism and nutrition disorders Hyperphosphatemia	0.00% 0/10 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Metabolism and nutrition disorders Hypokalemia	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Metabolism and nutrition disorders Acidosis	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Musculoskeletal and connective tissue disorders Bladder spasm	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Musculoskeletal and connective tissue disorders Tremor	0.00% 0/10 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Renal and urinary disorders Acute kidney injury	0.00% 0/10 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.
Renal and urinary disorders Delayed graft function	20.0% 2/10 • Number of events 2 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.	10.0% 1/10 • Number of events 1 • 1 year 6 months The definition of adverse event and/or serious adverse event, used to collect adverse event information is the same from clinicaltrials.gov.