HealthyPhase 1NCT00128947
Pharmacokinetics of Mycophenolate Mofetil in Healthy Volunteers
A Phase 1 study testing Mycophenolic Acid and Mycophenolate 7-O-Phenolic Glucuronide in people with Healthy, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Healthy
- What is being tested?
- Mycophenolic Acid and Mycophenolate 7-O-Phenolic Glucuronide
- How many people
- 130 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2005to May 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center (CC)
Bethesda, Maryland, 20892
About this study
Official title: Pharmacokinetics of Mycophenolic Acid and Mycophenolate 7-O-Phenolic Glucuronide in Healthy Subjects With or Without Two Common Genetic Polymorphisms in the Promoter Region of Uridine Diphosphate Glucuronosyltransferase 1A9
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.
Read more
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.
Read the detailed description
The immunosuppressant mycophenolate mofetil (MMF) is metabolized by several uridine diphosphate glucuronosyltransferases (UGTs), among which UGT1A9 is the most important enzyme. Two commonly occurring single nucleotide polymorphisms (SNPs) in the promoter region of the UGT1A9 gene have been shown to enhance UGT1A9 protein level and activity in vitro. This study is to investigate the potential in vivo effects of these two SNPs on the metabolism and hence the pharmacokinetics of MMF metabolites. One hundred and thirty healthy volunteers will be screened for the presence of UGT1A9 C-2152T and T-275A polymorphisms. Seventeen subjects who carry the variant alleles, along with 17 others who do not have the polymorphisms, will be selected to participate in the pharmacokinetic study. Pharmacokinetics of the metabolites mycophenolic acid (active) and mycophenolate 7-O-phenolic glucuronide (inactive) will be determined, and parameter values will be compared between the two groups. It is hypothesized that the metabolism of MMF is enhanced in subjects with the two SNPs, resulting in an increase in clearance and a decrease in the exposure of mycophenolic acid.
- Conditions
- Healthy
- Being tested
- Mycophenolic Acid, Mycophenolate 7-O-Phenolic Glucuronide
- Keywords
- Immunosuppresant, Pharmacogenetics, Glucuronidation, Metabolism, UGT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mycophenolic AcidDrug
Mycophenolate 7-O-Phenolic GlucuronideDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2005 (estimated)
- Study startJul 2005
- Study completionMay 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 130 participants
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00128947
- Sponsor's protocol ID
- 050209
- Other IDs
- 05-CC-0209
- Status last verified
- May 2006
- First submitted
- 9 Aug 2005
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
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.
PubMed 10878285Bullingham 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.
PubMed 8728345Srinivas 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.
PubMed 14640931
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Mycophenolic Acid and Mycophenolate 7-O-Phenolic Glucuronide in Healthy Subjects With or Without Two Common Genetic Polymorphisms in the Promoter Region of Uridine Diphosphate Glucuronosyltransferase 1A9
- ClinicalTrials.gov ID
- NCT00128947
- Acronym / sponsor ID
- 050209
- Conditions
- Healthy
- Keywords
- Immunosuppresant, Pharmacogenetics, Glucuronidation, Metabolism, UGT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- Jul 2005
- Study completion
- May 2006
- First posted
- 10 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The immunosuppressant mycophenolate mofetil (MMF) is metabolized by several uridine diphosphate glucuronosyltransferases (UGTs), among which UGT1A9 is the most important enzyme. Two commonly occurring single nucleotide polymorphisms (SNPs) in the promoter region of the UGT1A9 gene have been shown to enhance UGT1A9 protein level and activity in vitro. This study is to investigate the potential in vivo effects of these two SNPs on the metabolism and hence the pharmacokinetics of MMF metabolites. One hundred and thirty healthy volunteers will be screened for the presence of UGT1A9 C-2152T and T-275A polymorphisms. Seventeen subjects who carry the variant alleles, along with 17 others who do not have the polymorphisms, will be selected to participate in the pharmacokinetic study. Pharmacokinetics of the metabolites mycophenolic acid (active) and mycophenolate 7-O-phenolic glucuronide (inactive) will be determined, and parameter values will be compared between the two groups. It is hypothesized that the metabolism of MMF is enhanced in subjects with the two SNPs, resulting in an increase in clearance and a decrease in the exposure of mycophenolic acid.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolic Acid | Drug | – |
| Mycophenolate 7-O-Phenolic Glucuronide | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 10878285Allison 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.
- Background: PubMed 8728345Bullingham 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.
- Background: PubMed 14640931Srinivas 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mycophenolic Acid and Mycophenolate 7-O-Phenolic Glucuronide in people with Healthy, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00128947, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.