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

NCT02221583 | Completed Phase 4

• 1 other identifier: ASTA-14B02
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

End Stage Renal Disease

Keywords

End stage renal disease; Renal transplant candidate; Laparoscopic sleeve gastrectomy; Immunosuppressants

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (1)

• Adverse events (serious and non-serious)

  Study Day 1 and Day 8

Study Arms (2)

Group 1

EXPERIMENTAL

Astagraf XL + Mycophenolate mofetil then cross over to Prograf + Mycophenolate

Drug: Astagraf XL; Drug: Prograf; Drug: Mycophenolate mofetil

Group 2

EXPERIMENTAL

Prograf + Mycophenolate mofetil then cross over to Astagraf XL + Mycophenolate

Drug: Astagraf XL; Drug: Prograf; Drug: Mycophenolate mofetil

Interventions

Astagraf XL DRUG

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.

Also known as: Tacrolimus sustained release

Group 1; Group 2

Prograf DRUG

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.

Also known as: Tacrolimus

Group 1; Group 2

Mycophenolate mofetil DRUG

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.

Also known as: Cellcept

Group 1; Group 2

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male patient aged \> 18 years old.
• ESRD patient (on dialysis or preemptive) who is a potential candidate for kidney transplantation
• Undergone laparoscopic sleeve gastrectomy procedure \> 3 months prior to enrollment.
• Subjects have signed and dated the informed consent to participate in the study.

You may not qualify if:

• Patients taking a drug known to interact with Astagraf XL, Prograf®, or MMF.
• Patients that have an allergy to Astagraf XL, Prograf®, or MMF.
• Patients currently taking Astagraf XL, Prograf®, or MMF.
• Post-surgical leak complication
• Patients failing to adhere to post laparoscopic sleeve gastrectomy follow-up recommendations and clinic visits
• Patients with any severe medical condition requiring acute or chronic treatment that in the investigator's opinion would interfere with study participation.
• 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
• 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.
• 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.

Sponsors & Collaborators

• University of Cincinnati: lead
• Astellas Pharma Inc: collaborator

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Related Publications (1)

• Diwan TS, Lichvar AB, Leino AD, Vinks AA, Christians U, Shields AR, Cardi MA, Fukuda T, Mizuno T, Kaiser T, Woodle ES, Alloway RR. Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy. Clin Transplant. 2017 Jun;31(6). doi: 10.1111/ctr.12975. Epub 2017 May 2.

  PMID: 28342282 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Tayyab Diwan, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery

Study Record Dates

• First Submitted: August 13, 2014
• First Posted: August 20, 2014
• Study Start: May 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: May 12, 2015

Record last verified: 2015-05

Locations

US (1)