Trial Outcomes & Findings for Dosing Requirements of Astagraf XL® in African American Kidney Transplant Recipients (NCT NCT02953873)
NCT ID: NCT02953873
Last Updated: 2019-12-26
Results Overview
Difference in dose-normalized trough at steady state before and after conversion from tacrolimus IR to Astagraf XL®
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
25 participants
Primary outcome timeframe
Baseline to 3 months post-conversion
Results posted on
2019-12-26
Participant Flow
Participant milestones
| Measure |
Conversion Arm
Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dosing Requirements of Astagraf XL® in African American Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Conversion Arm
n=25 Participants
Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day
|
|---|---|
|
Age, Continuous
|
52 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Number of Days Since Transplant
|
270 days
n=5 Participants
|
|
Weight
|
94.5 kilograms
STANDARD_DEVIATION 23 • n=5 Participants
|
|
BMI
|
31.7 kg/m^2
STANDARD_DEVIATION 6.1 • n=5 Participants
|
|
Calculated Panel Reactive Antibodies (cPRA)
|
50 percent
n=5 Participants
|
|
Number of participants on Hemodialysis Prior to Transplant
|
23 Participants
n=5 Participants
|
|
Cold Ischemic Time
|
18.1 hours
n=5 Participants
|
|
Warm Ischemic Time
|
38.7 minutes
STANDARD_DEVIATION 7.1 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 3 months post-conversionDifference in dose-normalized trough at steady state before and after conversion from tacrolimus IR to Astagraf XL®
Outcome measures
| Measure |
Conversion Arm
n=25 Participants
Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day
|
|---|---|
|
Dose-normalized Trough
Pre-Conversion Dose Trough
|
0.59 ng/dL
Interval 0.5 to 0.76
|
|
Dose-normalized Trough
Post-Conversion Dose Trough
|
0.44 ng/dL
Interval 0.39 to 0.8
|
SECONDARY outcome
Timeframe: Baseline to 3 months post conversionDifference in Total Daily Dose necessary for steady state therapeutic goal
Outcome measures
| Measure |
Conversion Arm
n=25 Participants
Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day
|
|---|---|
|
Total Daily Dose
Pre-Conversion Tacrolimus Dose
|
10 mg
Interval 9.0 to 17.0
|
|
Total Daily Dose
Post-Conversion Tacrolimus Dose
|
15 mg
Interval 10.0 to 17.5
|
SECONDARY outcome
Timeframe: Baseline to 3 months post conversionWeight-based dose requirements to reach therapeutic goal pre- and post-conversion
Outcome measures
| Measure |
Conversion Arm
n=25 Participants
Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day
|
|---|---|
|
Weight-Based Dose Requirement
Pre-Conversion
|
0.11 mg/kg
Interval 0.1 to 0.17
|
|
Weight-Based Dose Requirement
Post-Conversion
|
0.16 mg/kg
Interval 0.11 to 0.2
|
SECONDARY outcome
Timeframe: Baseline to 3 months post conversionPopulation: Days to reach therapeutic goal was further separated by CYP3A5 1 expression.
Days to reach therapeutic goal after conversion
Outcome measures
| Measure |
Conversion Arm
n=25 Participants
Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day
|
|---|---|
|
Number of Days to Reach Therapeutic Trough Goal
Homozygous CYP3A5 1 expressors
|
15 number of days
Interval 5.0 to 25.0
|
|
Number of Days to Reach Therapeutic Trough Goal
Heterozygous CYP3A5 1 expressors
|
10 number of days
Interval 5.0 to 15.0
|
|
Number of Days to Reach Therapeutic Trough Goal
CYP3A5 1 non-expressors
|
15 number of days
Interval 15.0 to 15.0
|
SECONDARY outcome
Timeframe: Baseline to 3 months post conversionPopulation: 12 participants are homozygous, 10 are heterozygous, and 3 are non-expressors. This represents the 25 total subjects in the study.
Number of dose modifications from baseline to 3 months post-conversion.
Outcome measures
| Measure |
Conversion Arm
n=25 Participants
Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day
|
|---|---|
|
Dose Modifications
Homozygous CYP3A5 1 expressors
|
1 number of dose modifications
Interval 0.0 to 3.0
|
|
Dose Modifications
Heterozygous CYP3A5 1 expressors
|
2 number of dose modifications
Interval 0.0 to 2.0
|
|
Dose Modifications
CYP3A5 1 non expressers
|
4 number of dose modifications
Interval 1.0 to
The value is not applicable. There were only 3 values in the non-expressers, so a 75% interquartile range is not applicable.
|
Adverse Events
Conversion Arm
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Conversion Arm
n=25 participants at risk
Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day
|
|---|---|
|
Blood and lymphatic system disorders
Chronic myeloid Leukemia
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
Other adverse events
| Measure |
Conversion Arm
n=25 participants at risk
Tacrolimus Extended Release Capsule (goal 5 - 12ng/mL) + Mycophenolate Mofetil ≥500mg twice a day OR Mycophenolate Sodium ≥360mg twice a day+ prednisone ≥ 5mg Daily
Tacrolimus Extended Release Capsule: goal trough 5 - 12ng/mL
Mycophenolate mofetil: ≥500mg twice a day
Prednisone: goal dose 5mg daily
Mycophenolate Sodium: ≥360mg twice a day
|
|---|---|
|
Skin and subcutaneous tissue disorders
Alopecia
|
12.0%
3/25 • Number of events 3 • Adverse events were collected over 3 months
|
|
General disorders
Pain
|
20.0%
5/25 • Number of events 5 • Adverse events were collected over 3 months
|
|
Blood and lymphatic system disorders
Bleeding
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
|
Skin and subcutaneous tissue disorders
Skin infection (abscess)
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
|
Endocrine disorders
Hyperglycemia
|
8.0%
2/25 • Number of events 2 • Adverse events were collected over 3 months
|
|
General disorders
Gait disturbance
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
|
General disorders
Headache
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
|
Renal and urinary disorders
Urinary Tract Infection
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
|
Musculoskeletal and connective tissue disorders
Muscle Myositis
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
|
Blood and lymphatic system disorders
Chronic myeloid leukemia
|
4.0%
1/25 • Number of events 1 • Adverse events were collected over 3 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place