CYP3A4 InductionNCT01340456
Cholesterol Metabolites as Markers for CYP3A Induction
A study testing Rifampicin treatment in people with CYP3A4 Induction, run by Karolinska University Hospital at 1 site in Sweden.
Trial summary
The objectives of this study are: To investigate if the endogenous cholesterol metabolite, 4beta-OHcholesterol could be used as a marker for induction of cytochrome P450 (CYP) 3A4. To compare 4beta-OHcholesterol with midazolam as a marker for induction of CYP3A4. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- CYP3A4 Induction
- What is being tested?
- Rifampicin treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSweden
- Study dates
- May 2011to Jul 2011
- Phase
- Interventional
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Females and males.
- Age of 18 and above.
- Caucasians.
- Healthy as assessed by medical history and examination by principal investigator or delegated personnel.
- Accept to refrain from herbal drugs, natural preparations, and grapefruit juice 48 hours before and during the study period.
- Accept to completely refrain from alcohol during day -1 to 1 and R14-R16. During the rest of the study moderate alcohol use is permitted (equal to 1 glass of wine or 1 beer per day).
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- Women of childbearing age should accept using a reliable barrier contraceptive method throughout the study.
- Women of childbearing age should have a negative pregnancy test at the screening visit.
- Capable of following given instructions.
- Has given written informed consent after receiving both oral and written study information.
Who cannot join
- Predisposal to allergic drug reactions.
- Anamnestic and/or visual signs of infection.
- Women are not allowed to use oral hormone-based contraceptives 2 weeks before start of study and during the study.
- Participation in another study within one month before entering the present study.
- Intake of any other drug that can influence the enzyme activity of CYP3A4.
- Pregnancy.
- Breast-feeding.
- A history of liver disease.
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Clinical Pharmacology Trial Unit (CPTU), Karolinska University Hospital
Stockholm, SE-14186
About this study
Official title: Induction of Drug Metabolism by Rifampicin to Compare the Endogenous Biomarker 4beta-OHcholesterol With the Probe Drug Midazolam as Quantitative Markers for Cytochrome P450 3A4 Induction
The objectives of this study are:
- To investigate if the endogenous cholesterol metabolite, 4beta-OHcholesterol could be used as a marker for induction of cytochrome P450 (CYP) 3A4.
- To compare 4beta-OHcholesterol with midazolam as a marker for induction of CYP3A4.
- Conditions
- CYP3A4 Induction
- Being tested
- Rifampicin treatment
- Keywords
- 4beta-OHcholesterol, Midazolam, CYP3A4, Enzyme induction, Drug metabolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifampicin treatmentDrug
Also called Rifadin
induction of CYP3A4 with one of three rifampicin doses (10, 20, 100 mg QD)
| Study group | Role | What they receive |
|---|---|---|
| Rifampicin 10 mg QD | Experimental | Not described Receives: Drug: Rifampicin treatment |
| Rifampicin 20 mg QD | Experimental | Not described Receives: Drug: Rifampicin treatment |
| Rifampicin 100 mg QD | Experimental | Not described Receives: Drug: Rifampicin treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 4beta-OHcholesterol
The primary objective of the study is to investigate whether the endogenous cholesterol metabolite 4β-hydroxycholesterol could be used as a marker for induction of CYP3A4. For this purpose the induction of 4β-hydroxycholesterol formation will be compared to the induction of quinine and midazolam metabolism.
Measured: Directly before treatment with rifampicin and 14 days after the end of treatment with rifampicin
Secondary outcomes (1)
Ratio between midazolam AUC induced and midazolam AUC uninduced
Secondary aim of the study is to compare 4β-hydroxycholesterol as a biomarker for CYP3A4 compared to 6β-hydroxycortisol/cortisol ratio, which sometimes is used as a marker for CYP3A4 induction.
Another secondary aim is to relate our estimations of CYP3A4-expression to measured levels of 25-OH-vitamin D.
Measured: Before treatment with rifampicin and after 14 days of treatment with rifampicin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2011 (estimated)
- Study startMay 2011
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CYP3A4 InductionStudies of the same condition, open and under way.
- More trials run by Karolinska University HospitalThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Investigators
- Tobias Bäckström, MD PhD, Principal investigator, Department of Clinical Pharmacology, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01340456
- Sponsor's protocol ID
- 1001-01
- Status last verified
- May 2011
- First submitted
- 15 Apr 2011
- Last updated
- 11 Jul 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction of Drug Metabolism by Rifampicin to Compare the Endogenous Biomarker 4beta-OHcholesterol With the Probe Drug Midazolam as Quantitative Markers for Cytochrome P450 3A4 Induction
- ClinicalTrials.gov ID
- NCT01340456
- Acronym / sponsor ID
- 1001-01
- Conditions
- CYP3A4 Induction
- Keywords
- 4beta-OHcholesterol, Midazolam, CYP3A4, Enzyme induction, Drug metabolism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Karolinska University HospitalUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- May 2011
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 22 Apr 2011 (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 objectives of this study are:
- To investigate if the endogenous cholesterol metabolite, 4beta-OHcholesterol could be used as a marker for induction of cytochrome P450 (CYP) 3A4.
- To compare 4beta-OHcholesterol with midazolam as a marker for induction of CYP3A4.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rifampicin 10 mg QD | Experimental | Drug: Rifampicin treatment |
| Rifampicin 20 mg QD | Experimental | Drug: Rifampicin treatment |
| Rifampicin 100 mg QD | Experimental | Drug: Rifampicin treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Females and males.
- Age of 18 and above.
- Caucasians.
- Healthy as assessed by medical history and examination by principal investigator or delegated personnel.
- Accept to refrain from herbal drugs, natural preparations, and grapefruit juice 48 hours before and during the study period.
Key exclusion criteria (8 listed)
- Predisposal to allergic drug reactions.
- Anamnestic and/or visual signs of infection.
- Women are not allowed to use oral hormone-based contraceptives 2 weeks before start of study and during the study.
- Participation in another study within one month before entering the present study.
- Intake of any other drug that can influence the enzyme activity of CYP3A4.
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 |
|---|---|---|
| Rifampicin treatmentAlso: Rifadininduction of CYP3A4 with one of three rifampicin doses (10, 20, 100 mg QD) | Drug | Rifampicin 10 mg QD, Rifampicin 100 mg QD, Rifampicin 20 mg QD |
Primary outcome
Change in 4beta-OHcholesterol
Time frame: Directly before treatment with rifampicin and 14 days after the end of treatment with rifampicin
The primary objective of the study is to investigate whether the endogenous cholesterol metabolite 4β-hydroxycholesterol could be used as a marker for induction of CYP3A4. For this purpose the induction of 4β-hydroxycholesterol formation will be compared to the induction of quinine and midazolam metabolism.
1 secondary outcome
Ratio between midazolam AUC induced and midazolam AUC uninduced
Time frame: Before treatment with rifampicin and after 14 days of treatment with rifampicin
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 11 Jul 2011.
Related trials for CYP3A4 Induction
Not yet recruitingPhase 1
A Study to Assess the Potential CYP3A Induction Effect of Brensocatib on the Pharmacokinetics (PK) of Midazolam in Healthy Participants
Healthy Volunteers
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.
Tobias Bäckström, MD PhD principal investigator
Department of Clinical Pharmacology, Karolinska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rifampicin treatment in people with CYP3A4 Induction, run by Karolinska University Hospital at 1 site in Sweden.
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 10 inclusion and 8 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 11 Jul 2011. 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 Sweden. 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.
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?
Change in 4beta-OHcholesterol (time frame: Directly before treatment with rifampicin and 14 days after the end of treatment with rifampicin). 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 11 Jul 2011.