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

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ClinicalTrials.gov Identifier: NCT02221583
Recruitment Status : Completed
First Posted : August 20, 2014
Last Update Posted : May 12, 2015
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Tayyab Diwan, University of Cincinnati

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.

Condition or disease Intervention/treatment Phase
End Stage Renal Disease Drug: Astagraf XL Drug: Prograf Drug: Mycophenolate mofetil Phase 4

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
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
Study Start Date : May 2014
Actual Primary Completion Date : February 2015
Actual Study Completion Date : February 2015


Arm Intervention/treatment
Experimental: Group 1
Astagraf XL + Mycophenolate mofetil then cross over to Prograf + Mycophenolate
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.
Other Name: Tacrolimus sustained release

Drug: 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.
Other Name: Tacrolimus

Drug: 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.
Other Name: Cellcept

Experimental: Group 2
Prograf + Mycophenolate mofetil then cross over to Astagraf XL + Mycophenolate
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.
Other Name: Tacrolimus sustained release

Drug: 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.
Other Name: Tacrolimus

Drug: 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.
Other Name: Cellcept




Primary Outcome Measures :
  1. Area Under Curve (AUC) [ Time Frame: 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 ]
    AUC of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8

  2. Maximum concentration (Cmax) [ Time Frame: 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 ]
    Cmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8

  3. Time to maximum concentration (Tmax) [ Time Frame: 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 ]
    Tmax of tacrolimus, MMF and their metabolites will be measured at 18 timepoints within 24 hour period on Study Day 1 and Day 8

  4. Half life (T 1/2) [ Time Frame: 24 hours ]
    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


Secondary Outcome Measures :
  1. Adverse events (serious and non-serious) [ Time Frame: Study Day 1 and Day 8 ]
    All serious adverse events and non-serious adverse events as reported by the subject will be recorded



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02221583


Locations
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Sponsors and Collaborators
University of Cincinnati
Astellas Pharma Inc
Investigators
Principal Investigator: Tayyab Diwan, MD University of Cincinnati

Responsible Party: Tayyab Diwan, Assistant Professor of Surgery, University of Cincinnati
ClinicalTrials.gov Identifier: NCT02221583     History of Changes
Other Study ID Numbers: ASTA-14B02
First Posted: August 20, 2014    Key Record Dates
Last Update Posted: May 12, 2015
Last Verified: May 2015

Keywords provided by Tayyab Diwan, University of Cincinnati:
End stage renal disease
Renal transplant candidate
Laparoscopic sleeve gastrectomy
Immunosuppressants

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Tacrolimus
Immunosuppressive Agents
Mycophenolic Acid
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents