Dosing Requirements of Astagraf XL® in African American Kidney Transplant Recipients

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT02953873
• Collaborator: Astellas Pharma Inc (Industry)
• Enrollment: 25
• Location: 1
• Arm: 1
• Actual Duration (Months): 19.3
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

Compare the difference in dose-normalized trough and total daily dose necessary to reach the steady state therapeutic goal after conversion from tacrolimus IR to Astagraf XL® in African American kidney transplant recipients.

Condition or Disease	Intervention/Treatment	Phase
Immunosuppression	Drug: Tacrolimus Extended Release Capsule; Drug: Mycophenolate mofetil; Drug: Prednisone; Drug: Mycophenolate Sodium	Phase 4

Detailed Description

The purpose of this study is to compare the difference in medication dosage and total daily dose necessary of Astagraf XL® in order to reach therapy goal, when taken with other medications that are routinely used for kidney transplantation, which may stop the development of a substance that can cause long-term damage to the transplanted kidney. African American kidney transplant patients aged 18 and above who are underwent a kidney transplant are eligible to participate. The duration of the study is 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dosing Requirements of Astagraf XL® in African American Kidney Transplant Recipients Converted From Twice-daily Tacrolimus
• Actual Study Start Date: May 5, 2017
• Actual Primary Completion Date: Sep 10, 2018
• Actual Study Completion Date: Dec 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: 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	Drug: Tacrolimus Extended Release Capsule; goal trough 5 - 12ng/mL; Other Names: Astagraf XL ; Drug: Mycophenolate mofetil; ≥500mg twice a day; Other Names: Cellcept ; Drug: Prednisone; goal dose 5mg daily; Other Names: Corticosteroids Methylprednisolone ; Drug: Mycophenolate Sodium; ≥360mg twice a day; Other Names: Myfortic

Outcome Measures

Primary Outcome Measures

1. Dose-normalized Trough [Baseline to 3 months post-conversion]

   Difference in dose-normalized trough at steady state before and after conversion from tacrolimus IR to Astagraf XL®

Secondary Outcome Measures

1. Total Daily Dose [Baseline to 3 months post conversion]

   Difference in Total Daily Dose necessary for steady state therapeutic goal

2. Weight-Based Dose Requirement [Baseline to 3 months post conversion]

   Weight-based dose requirements to reach therapeutic goal pre- and post-conversion

3. Number of Days to Reach Therapeutic Trough Goal [Baseline to 3 months post conversion]

   Days to reach therapeutic goal after conversion

4. Dose Modifications [Baseline to 3 months post conversion]

   Number of dose modifications from baseline to 3 months post-conversion.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. At least 18 years of age

2. Signed informed consent

3. African American race

4. History of a solitary renal transplant

5. Stable tacrolimus dose for at least 2 weeks prior to randomization

Exclusion Criteria:

1. A condition or disorder that, in the opinion of the investigator, may adversely affect the outcome of the study or the safety of the subject

2. Currently enrolled in an investigational drug trial

3. History of a non-renal organ transplant

4. History of acute cellular rejection within 1 month prior to randomization

5. An increase in serum creatinine by > 20% in the 2 weeks prior to randomization

6. Maintenance immunosuppression that does not consist of tacrolimus IR given twice daily, mycophenolate mofetil > 1000mg TDD or mycophenolate sodium > 720mg TDD, and prednisone ≥ 5mg daily

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• Astellas Pharma Inc

Investigators

• Principal Investigator: James Fleming, PharmD, Medicual U of South Carolina

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 12, 2017

More Information

Publications

None provided.

• Responsible Party: James N. Fleming, Principal Investigator, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT02953873
• Other Study ID Numbers: 00061221
• First Posted: Nov 3, 2016
• Last Update Posted: Dec 26, 2019
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Mycophenolic Acid; Prednisone; Methylprednisolone; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Conversion Arm
Arm/Group Description	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
Period Title: Overall Study
STARTED	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Conversion Arm
Arm/Group Description	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 Participants	25
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	52
Sex: Female, Male (Count of Participants)
Female	13 52%
Male	12 48%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	25 100%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Number of Days Since Transplant (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]	270
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	94.5 (23)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.7 (6.1)
Calculated Panel Reactive Antibodies (cPRA) (percent) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [percent]	50
Number of participants on Hemodialysis Prior to Transplant (Count of Participants)
Count of Participants [Participants]	23 92%
Cold Ischemic Time (hours) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [hours]	18.1
Warm Ischemic Time (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	38.7 (7.1)

Outcome Measures

1. Primary Outcome

Title	Dose-normalized Trough
Description	Difference in dose-normalized trough at steady state before and after conversion from tacrolimus IR to Astagraf XL®
Time Frame	Baseline to 3 months post-conversion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conversion Arm
Arm/Group Description	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
Measure Participants	25
Pre-Conversion Dose Trough	0.59
Post-Conversion Dose Trough	0.44

2. Secondary Outcome

Title	Total Daily Dose
Description	Difference in Total Daily Dose necessary for steady state therapeutic goal
Time Frame	Baseline to 3 months post conversion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conversion Arm
Arm/Group Description	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
Measure Participants	25
Pre-Conversion Tacrolimus Dose	10
Post-Conversion Tacrolimus Dose	15

3. Secondary Outcome

Title	Weight-Based Dose Requirement
Description	Weight-based dose requirements to reach therapeutic goal pre- and post-conversion
Time Frame	Baseline to 3 months post conversion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conversion Arm
Arm/Group Description	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
Measure Participants	25
Pre-Conversion	0.11
Post-Conversion	0.16

4. Secondary Outcome

Title	Number of Days to Reach Therapeutic Trough Goal
Description	Days to reach therapeutic goal after conversion
Time Frame	Baseline to 3 months post conversion

Outcome Measure Data

Analysis Population Description

Days to reach therapeutic goal was further separated by CYP3A5 1 expression.

Arm/Group Title	Conversion Arm
Arm/Group Description	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
Measure Participants	25
Homozygous CYP3A5 1 expressors	15
Heterozygous CYP3A5 1 expressors	10
CYP3A5 1 non-expressors	15

5. Secondary Outcome

Title	Dose Modifications
Description	Number of dose modifications from baseline to 3 months post-conversion.
Time Frame	Baseline to 3 months post conversion

Outcome Measure Data

Analysis Population Description

12 participants are homozygous, 10 are heterozygous, and 3 are non-expressors. This represents the 25 total subjects in the study.

Arm/Group Title	Conversion Arm
Arm/Group Description	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
Measure Participants	25
Homozygous CYP3A5 1 expressors	1
Heterozygous CYP3A5 1 expressors	2
CYP3A5 1 non expressers	4

Adverse Events

Time Frame	Adverse events were collected over 3 months
Arm/Group Title	Conversion Arm
Arm/Group Description	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
All Cause Mortality
	Conversion Arm
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Serious Adverse Events
	Conversion Arm
	Affected / at Risk (%)	# Events
Total	1/25 (4%)
Blood and lymphatic system disorders
Chronic myeloid Leukemia	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Conversion Arm
	Affected / at Risk (%)	# Events
Total	19/25 (76%)
Blood and lymphatic system disorders
Bleeding	1/25 (4%)	1
Chronic myeloid leukemia	1/25 (4%)	1
Endocrine disorders
Hyperglycemia	2/25 (8%)	2
General disorders
Pain	5/25 (20%)	5
Gait disturbance	1/25 (4%)	1
Headache	1/25 (4%)	1
Metabolism and nutrition disorders
Hypomagnesemia	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Muscle Myositis	1/25 (4%)	1
Renal and urinary disorders
Urinary Tract Infection	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Alopecia	3/25 (12%)	3
Skin infection (abscess)	1/25 (4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.