Pharmacokinetics of Immunosuppressants in Renal Transplant Candidates Who Have Undergone Laparoscopic Sleeve Gastrectomy

End Stage Renal Disease Clinical Trial

Official title:

A Multicenter Pilot Study to Determine the Pharmacokinetics of Astagraf XL, Prograf and Mycophenolate Mofetil in Renal Transplant Candidates Who Have Undergone Laparoscopic Sleeve Gastrectomy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02221583
• Other study ID #: ASTA-14B02
• Status: Completed
• Phase: Phase 4
• First received: August 13, 2014
• Last updated: May 11, 2015
• Start date: May 2014
• Est. completion date: February 2015

Study information

• Verified date: May 2015
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate how quickly and to what extent different immunosuppressants are absorbed into the blood (this is called pharmacokinetics) in renal transplant candidates who have undergone a laparoscopic sleeve gastrectomy. The immune system is the body's defense against diseases. It also attacks "foreign" tissues such as a transplanted kidney. Immunosuppressant medications such as Astagraf sustained release (XL), Prograf, and mycophenolate mofetil may be given to suppress the immune system following kidney transplantation and prevent rejection of a transplanted kidney. This study is being performed to determine if patients who undergo laparoscopic sleeve gastrectomy need different doses of immunosuppressant medications.

Description:

Investigators propose a single dose, cross over pharmacokinetic study of Astagraf XL and Prograf® in combination with MMF in RTx candidates that have undergone LSG. Subjects at least three months post LSG and pre-renal transplant will undergo preliminary screening. The study population will consist of 24 male and female subjects, ≥ 18 years old from UC Health University Hospital and The Christ Hospital who meet the inclusion/exclusion criteria.

Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated. The immunosuppressants chosen reflect the regimen most commonly prescribed to transplant recipients.

Subjects participating in the study will have pharmacokinetic blood samples drawn over a 24 hour time period in order to determine the AUC, Tmax, Cmax, and half-life of tacrolimus, MMF and their metabolites. Samples would be drawn prior to dosing (C0) and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing (18 time points) by venipuncture or IV.

This study proposal represents a simple and expeditious method to achieve PK information in patients that have undergone LSG. If desired, study could be expanded to evaluate PK in additional patient groups such as pre and post LSG and/or pre and post renal transplant. The exact sample collection time will be recorded in the case report form. All deviations from the scheduled sampling time of more than 5 minutes for the first 4 hours after the AM dose (predose-4 hr) and first 4 hours of the PM dose (12 hr-16 hr), and more than 10 minutes for all remaining samples (6 hr-8 hr; 18 hr-24 hr) will be reported as a protocol deviation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Female or male patient aged > 18 years old.

2. ESRD patient (on dialysis or preemptive) who is a potential candidate for kidney transplantation

3. Undergone laparoscopic sleeve gastrectomy procedure > 3 months prior to enrollment.

4. Subjects have signed and dated the informed consent to participate in the study.

Exclusion Criteria:

1. Patients taking a drug known to interact with Astagraf XL, Prograf®, or MMF.

2. Patients that have an allergy to Astagraf XL, Prograf®, or MMF.

3. Patients currently taking Astagraf XL, Prograf®, or MMF.

4. Post-surgical leak complication

5. Patients failing to adhere to post laparoscopic sleeve gastrectomy follow-up recommendations and clinic visits

6. Patients with any severe medical condition requiring acute or chronic treatment that in the investigator's opinion would interfere with study participation.

7. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive laboratory test

8. Currently taking or planning to initiate of any medications that could interfere with tacrolimus and/or mycophenolate blood levels, including over the counter (OTC) medications, herbal supplements, grapefruit or grapefruit juice.

9. Subjects who have been exposed to an investigational therapy within 30 days prior to enrollment or 5 half-lives of the investigational product, whichever is greater.

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• Astagraf XL
Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.
• Prograf
Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.
• Mycophenolate mofetil
Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.

Locations

Country	Name	City	State
United States	University of Cincinnati	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University of Cincinnati	Astellas Pharma Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under Curve (AUC)	AUC of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8	Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
Primary	Maximum concentration (Cmax)	Cmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8	Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
Primary	Time to maximum concentration (Tmax)	Tmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8	Prior to dosing (CO), and at 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing
Primary	Half life (T 1/2)	Half-life of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8	24 hours
Secondary	Adverse events (serious and non-serious)	All serious adverse events and non-serious adverse events as reported by the subject will be recorded	Study Day 1 and Day 8