PharmacokineticsPhase 1NCT00621101
Pharmacokinetic Drug Interaction Between Ezetimibe and Sirolimus After Single Dose Administration in Healthy Subjects
A Phase 1 study testing 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany, 1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, Germany and 1 tablet Ezetrol(R) + 1 tablet Rapamune(R) in people with Pharmacokinetics and Drug Interactions, run by University Medicine Greifswald at 1 site in Germany.
Trial summary
The purpose of this study is to confirm a significant influence of ezetimibe and sirolimus on each others pharmacokinetics Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics, Drug Interactions, Hypercholesterolemia
- What is being tested?
- 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany, 1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, Germany and 1 tablet Ezetrol(R) + 1 tablet Rapamune(R)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2007to Jun 2007
- 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 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- age: 18 - 45 years
- sex: male and female
- ethnic origin: Caucasian
- body weight: 19 kg/m² to 27 kg/m²
- good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
- written informed consent
Who cannot join
- known allergy to macrolide antibiotics
- existing cardiac or hematological diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
- existing hepatic and renal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
- existing gastrointestinal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
- acute or chronic diseases which could affect drug absorption or metabolism
- history of any serious psychological disorder
Show all 25Show fewer
- drug or alcohol dependence
- positive drug or alcohol screening
- smokers of 10 or more cigarettes per day
- positive screening results for HIV, HBV and HCV
- volunteers who are on a diet which could affect the pharmacokinetics of the drug
- heavy tea or coffee drinkers (more than 1L per day)
- lactation and pregnancy test positive or not performed
- volunteers suspected or known not to follow instructions
- volunteers who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
- volunteers liable to orthostatic dysregulation, fainting, or blackouts
- blood donation or other blood loss of more than 400 ml within the last 12 weeks prior to the start of the study
- participation in a clinical trial during the last 3 months prior to the start of the study
- less than 14 days after last acute disease
- any systemically available medication within 4 weeks prior to the intended first administration unless, because of the terminal elimination half-life, complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives)
- repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence hepatic biotransformation (e.g. barbiturates, cimetidine, phenytoin, rifampicin)
- repeated use of drugs during the last 2 weeks prior to the intended first administration which affect absorption (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists)
- intake of grapefruit containing food or beverages within 7 days prior to administration
- known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparation
- subjects with severe allergies or multiple drug allergies
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to confirm a significant influence of ezetimibe and sirolimus on each others pharmacokinetics
Read the detailed description
Hypercholesterolemia is a frequent finding in organ transplant recipients receiving immunosuppressive drugs such as sirolimus. To prevent increased cardiovascular morbidity and mortality in these patients, co-medication with lipid-lowering statins is recommended. However, treatment with statins is limited in many patients by insufficient cholesterol-lowering efficacy, drug interactions and serious adverse drug reactions (e.g. rhabdomyolysis). These patients may benefit from comedication with the cholesterol absorption inhibitor ezetimibe (EZE). Since SIR and EZE were shown to be substrates of the efflux transporter ABCB1 (P-glycoprotein), drug interactions between both compounds may occur. Therefore, this clinical study in healthy subjects was initiated to evaluate the clinical relevance of drug/drug interactions between sirolimus and ezetimibe according to the accepted bioequivalence approach.
- Being tested
- 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany, 1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, Germany, 1 tablet Ezetrol(R) + 1 tablet Rapamune(R)
- Keywords
- pharmacokinetics, drug interactions, ezetimibe, sirolimus, human experimentation
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, GermanyDrug
Also called Ezetrol
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe), 0-144 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-10 d feces sampling
1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, GermanyDrug
Also called Rapamune
administration of 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus), 0-144 h blood sampling
1 tablet Ezetrol(R) + 1 tablet Rapamune(R)Drug
Also called Ezetrol+Rapamune
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus), 0-144 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-10 d feces sampling
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) Receives: Drug: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany |
| B | Active comparator | administration of 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus) Receives: Drug: 1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, Germany |
| C | Experimental | administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus) Receives: Drug: 1 tablet Ezetrol(R) + 1 tablet Rapamune(R) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for sirolimus: AUC0-∞, Cmax
Measured: April 2007 to June 2007
Secondary outcomes (1)
Second. characteristics: for ezetimibe: CLR, Ae (urine), Ae (feces); for ezetimibe glucuronide: AUC0-∞, Cmax, Ae (urine), Ae (feces); for ezetimibe, ezetimibe glucuronide and sirolimus: AUC0-t, t½, tmax
Measured: April 2007 to June 2007
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2008 (estimated)
- Study startApr 2007
- Primary completionJun 2007
- Study completionJun 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacokineticsStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medicine Greifswald
- Sponsor type
- University, hospital or other
- Investigators
- Werner Siegmund, Prof, Principal investigator, Department of Clinical Pharmacology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00621101
- Sponsor's protocol ID
- Eze-Siro
- Other IDs
- EudraCT-No. 2006-006597-18
- Status last verified
- Feb 2008
- First submitted
- 12 Feb 2008
- Last updated
- 22 Feb 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Drug Interaction Between Ezetimibe and Sirolimus After Single Dose Administration in Healthy Subjects
- ClinicalTrials.gov ID
- NCT00621101
- Acronym / sponsor ID
- Eze-Siro
- Keywords
- pharmacokinetics, drug interactions, ezetimibe, sirolimus, human experimentation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Medicine GreifswaldUniversity, hospital or other
- Study start
- Apr 2007
- Primary completion
- Jun 2007 (actual)
- Study completion
- Jun 2007 (actual)
- First posted
- 22 Feb 2008 (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.
The purpose of this study is to confirm a significant influence of ezetimibe and sirolimus on each others pharmacokinetics
Detailed description
Hypercholesterolemia is a frequent finding in organ transplant recipients receiving immunosuppressive drugs such as sirolimus. To prevent increased cardiovascular morbidity and mortality in these patients, co-medication with lipid-lowering statins is recommended. However, treatment with statins is limited in many patients by insufficient cholesterol-lowering efficacy, drug interactions and serious adverse drug reactions (e.g. rhabdomyolysis). These patients may benefit from comedication with the cholesterol absorption inhibitor ezetimibe (EZE). Since SIR and EZE were shown to be substrates of the efflux transporter ABCB1 (P-glycoprotein), drug interactions between both compounds may occur. Therefore, this clinical study in healthy subjects was initiated to evaluate the clinical relevance of drug/drug interactions between sirolimus and ezetimibe according to the accepted bioequivalence approach.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germanyadministration of 1 tablet Ezetrol(R) (10 mg ezetimibe) |
| B | Active comparator | Drug: 1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, Germanyadministration of 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus) |
| C | Experimental | Drug: 1 tablet Ezetrol(R) + 1 tablet Rapamune(R)administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- age: 18 - 45 years
- sex: male and female
- ethnic origin: Caucasian
- body weight: 19 kg/m² to 27 kg/m²
- good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
Key exclusion criteria (25 listed)
- known allergy to macrolide antibiotics
- existing cardiac or hematological diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
- existing hepatic and renal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
- existing gastrointestinal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
- acute or chronic diseases which could affect drug absorption or metabolism
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 |
|---|---|---|
| 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, GermanyAlso: Ezetroladministration of 1 tablet Ezetrol(R) (10 mg ezetimibe), 0-144 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-10 d feces sampling | Drug | A |
| 1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, GermanyAlso: Rapamuneadministration of 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus), 0-144 h blood sampling | Drug | B |
| 1 tablet Ezetrol(R) + 1 tablet Rapamune(R)Also: Ezetrol+Rapamuneadministration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 5 ml Rapamune(R) oral solution (1 mg/ml sirolimus), 0-144 h blood sampling, 0-5 d urine sampling (24 h intervals) and 0-10 d feces sampling | Drug | C |
Primary outcome
Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for sirolimus: AUC0-∞, Cmax
Time frame: April 2007 to June 2007
1 secondary outcome
Second. characteristics: for ezetimibe: CLR, Ae (urine), Ae (feces); for ezetimibe glucuronide: AUC0-∞, Cmax, Ae (urine), Ae (feces); for ezetimibe, ezetimibe glucuronide and sirolimus: AUC0-t, t½, tmax
Time frame: April 2007 to June 2007
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 22 Feb 2008.
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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.
Werner Siegmund, Prof principal investigator
Department of Clinical Pharmacology
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 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany, 1 tablet Rapamune(R) (sirolimus), Wyeth Pharma, Germany and 1 tablet Ezetrol(R) + 1 tablet Rapamune(R) in people with Pharmacokinetics and Drug Interactions, run by University Medicine Greifswald at 1 site in Germany.
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 6 inclusion and 25 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 22 Feb 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 Germany. 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.
What does the primary outcome measure?
Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for sirolimus: AUC0-∞, Cmax (time frame: April 2007 to June 2007). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Feb 2008.