Pharmacokinetics of Mycophenolate Mofetil in Healthy Volunteers

NCT00128947 | Completed Phase 1

• 2 other identifiers: 05020905-CC-0209
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine how people differ in the way their bodies process and eliminate mycophenolate mofetil (MMF), a drug that is used to treat problems affecting the eye and immune system and to prevent organ rejection in transplant patients. MMF is metabolized by a group of enzymes called UGTs, each of which is made by a different gene. This study will investigate whether people with different UGT genes differ in how well their bodies use and remove MMF. The results may help scientists learn the best way to give MMF to patients. Normal healthy volunteers between 18 and 55 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood and urine tests, including a blood test for analysis of genes that control and regulate UGTs. Pregnant women and nursing mothers are excluded from the study. Women who are able to have a child and men who can father a child must either abstain from sex or use two reliable forms of birth control during the study and for 3 months after its completion. Participants come to the NIH Clinical Center at 6:30 a.m. on the first day of the study and stay in the outpatient clinic for 12 hours. The next 4 mornings, they return to the Clinical Center for a single blood collection. The procedures for the 5 days are as follows: Day 1 Upon arrival at the Clinical Center a catheter is inserted into the subject's arm vein. At 7:00 AM, the subject takes one dose of MMF by mouth with a glass of water. Small blood samples are collected through the catheter before the MMF dose and again at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours after taking the drug. Heart rate and blood pressure are measured before the blood collection and then every 4 hours. After the last blood sample is collected, the volunteer can return home. Days 2-5 Volunteers come to the Clinical Center at 7:00 AM on study days 2, 3, 4, and 5 for a single blood draw, collected using a needle. Volunteers are contacted by telephone 1, 2, and 3 months after completing the study to see how they are doing and to check on their pregnancy status and use of appropriate birth control.

Conditions

Healthy

Keywords

Immunosuppresant; Pharmacogenetics; Glucuronidation; Metabolism; UGT

Interventions

Mycophenolic Acid DRUG

Mycophenolate 7-O-Phenolic Glucuronide DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Normal healthy volunteers who are in good health as determined by medical history, physical examination, and baseline laboratory tests
• Age 18 - 55
• Both males and females
• Willingness to practice effective contraception during the study and for three months after the administration of MMF for women who are sexually active and have child bearing potential, and for sexually active males who have the potential to father a child. Barrier or non-hormonal methods will be allowed during the study, whereas the use of oral, injectable, or implantable hormones will be prohibited since drug interaction is known to occur between oral contraceptives and mycophenolate mofetil.
• Subjects who are able to understand and sign the informed consent form.

You may not qualify if:

• Children and adolescents less than 18 years of age
• Individuals who smoke or have excessive alcohol (greater than 1 beer or an equivalent alcoholic beverage per day)
• Pregnant women and nursing mothers
• Subjects with certain underlying diseases which include diabetes, cardiovascular diseases, liver diseases, cancer, and human immunodeficiency virus infection
• Individuals with compromised immune systems
• Subjects who have an active infection
• Individuals with history of biliary tract disease, and biliary or gastrointestinal surgery
• Subjects with persistent diarrhea or other gastrointestinal problems that could impede drug absorption
• Subjects with abnormal liver and kidney functions as determined by medication history and laboratory evaluation (AST and ALT less than or equal to 2 x upper normal limit, total bilirubin less than or equal to 1 mg/dL, serum creatinine less than or equal to 1.2 mg/dL, hemoglobin greater than or equal to 11 g/dL, WBC greater than or equal to 3.5 x 10(9)/L)
• Volunteers on chronic prescribed and over-the-counter medications, and dietary and herbal supplements within 4 weeks of study participation
• Subjects who are taking any medications that could potentially interact with MMF pharmacokinetically and pharmacodynamically such as eccinacea, iron preparations, antacids, bile-resin cholesterol lowering agents, and steroids.
• Volunteers with documented allergy to MMF
• Prior enrollment into a similar study within the past two months and enrollment in another study at the same time
• Subjects who are felt to be unwilling or unable to practice effective contraception methods or comply with protocol specifications

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center (CC)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000 May;47(2-3):85-118. doi: 10.1016/s0162-3109(00)00188-0.

  PMID: 10878285 BACKGROUND

• Bullingham R, Monroe S, Nicholls A, Hale M. Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration. J Clin Pharmacol. 1996 Apr;36(4):315-24. doi: 10.1002/j.1552-4604.1996.tb04207.x.

  PMID: 8728345 BACKGROUND

• Srinivas TR, Kaplan B, Meier-Kriesche HU. Mycophenolate mofetil in solid-organ transplantation. Expert Opin Pharmacother. 2003 Dec;4(12):2325-45. doi: 10.1517/14656566.4.12.2325.

  PMID: 14640931 BACKGROUND

MeSH Terms

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: August 9, 2005
• First Posted: August 10, 2005
• Study Start: July 1, 2005
• Study Completion: May 1, 2006
• Last Updated: March 4, 2008

Record last verified: 2006-05

Locations

US (1)