Boceprevir and Ucalm (St John&Apos;s Wort)

Hepatitis C Clinical Trial

Official title: Phase I Evaluation of the Pharmacokinetics and Safety of Boceprevir and Ucalm (St John&Apos;s Wort) When Co-administered to Male and Female Healthy Volunteers.

Status Completed

Clinical Trial Summary

The purpose of the study is to look at whether taking a new medication for hepatitis C (boceprevir) together with a herbal remedy commonly used for the treatment of depression (SJW) has any effect on the levels of boceprevir in the blood, compared to when boceprevir is taken on its own.

Treatment of hepatitis C genotype-1, has recently been significantly improved with the addition of a new class of drugs called protease inhibitors (PIs). Boceprevir belongs to this class of antiviral drugs and it is administered in combinations with other drugs to treat hepatitis C. One of the common side effects of treatment for hepatitis C is low mood (depression) for which treated patients may self-medicate with preparations containing St. Johns Wort (SJW).

SJW is known to cause drug interactions, so taking SJW at the same time as boceprevir may result in a change in how both of these drugs usually work. It is therefore important to find out if the levels of boceprevir in the blood are significantly affected by taking SJW.

The study aims to help us understand whether it will be safe to take SJW whilst being simultaneously treated for hepatitis C with boceprevir.

Clinical Trial Description

Boceprevir is a strong inhibitor of CYP3A4/5. Medicines metabolized primarily by CYP3A4/5 may have increased exposure when administered with boceprevir, which could increase or prolong their therapeutic and adverse reactions. Boceprevir does not inhibit or induce the other enzymes of the CYP450 family.

Boceprevir has been shown to be a P-glycoprotein and breast cancer resistant protein (BCRP) substrate in vitro. There is potential for inhibitors or inducers of these transporters to alter the concentrations of boceprevir; the clinical implications of these interactions are not known.Boceprevir is partly metabolized by CYP3A4/5. Co-administration of boceprevir with medicines that induce or inhibit CYP3A4/5 could increase or decrease exposure to boceprevir and affect its efficacy.Boceprevir, in combination with peginterferon and ribavirin, is contraindicated when coadministered with medicines that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Examples may include; orally administered midazolam and triazolam, bepridil, pimozide, lumefantrine, halofantrine, and tyrosine kinase inhibitors, and ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine).

Boceprevir is primarily metabolized by aldoketo reductase (AKR). In medicine interaction trials conducted with AKR inhibitors diflunisal and ibuprofen, boceprevir exposure did not increase to a clinically significant extent. Boceprevir may be co-administered with AKR inhibitors. The concomitant use of boceprevir with stong CYP3A4 inducers such as rifampicin or anticonvulsants (such as phenytoin, phenobarbital or carbamazepine) may significantly reduce the plasma exposure of boceprevir. As no data is available, the combination of boceprevir with these medicines is not recommended.

The metabolism of St John's Wort is not currently known. Treatment with St John's wort for 14 days resulted in significant increases in the urinary 6-beta-hydroxycortisol/ cortisol ratio, suggesting that St John's wort is an inducer of CYP3A4. For this reason, it is not recommended to administer SJW with CYP3A4 metabolized drugs. Furthermore,interactions may occur with P-glycoprotein substrates, as St. John's wort can induce the activity of transmembrane transporters. This might decrease the effectiveness of some medications.

For the reasons illustrated above, the potential for a drug interaction between SJW and boceprevir is high and the co-administration must be studied in order to gain information on whether: i) SJW leads to a decrease in boceprevir concentrations and therefore efficacy; ii) boceprevir leads to an increase in SJW (hypericin) exposure with risk of toxicity.

The safety and PK of the combination should be known especially in view of the common side effects caused by interferon, which is co-administered with boceprevir for the treatment of hepatitis C: as interferon causes depression, patients may chose to take SJW rather than prescribed anti-depressants to manage their mood changes during antihepatitis treatment. ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hepatitis C

• NCT number: NCT01663922
• Study type: Interventional
• Source: St Stephens Aids Trust
• Status: Completed
• Phase: Phase 1
• Start date: August 2012
• Completion date: December 2012