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Completed

NCT Number: NCT01340456

Cholesterol Metabolites as Markers for CYP3A 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.

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Key information

Conditions

CYP3A4 Induction

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Clinical Pharmacology Trial Unit (CPTU), Karolinska University Hospital

Stockholm, SE-14186, Sweden

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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).
  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Rifampicin treatment

Drug

induction of CYP3A4 with one of three rifampicin doses (10, 20, 100 mg QD)

Other names: Rifadin

Primary outcomes

  1. 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.

Secondary outcomes

  1. Ratio between midazolam AUC induced and midazolam AUC uninduced

    Time frame: Before treatment with rifampicin and after 14 days of treatment with rifampicin

    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.

Sponsors and collaborators

Lead sponsor

Karolinska University Hospital

Other

Collaborators

  • AstraZeneca

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2011
Study completion
2011
First posted
Apr 22, 2011
Registry last updated
Jul 11, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.