Hepatitis CPhase 1NCT01663922
Boceprevir and Ucalm (St John&Apos;s Wort)
A Phase 1 study testing Boceprevir and St John's Wort in people with Hepatitis C, run by St Stephens Aids Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Boceprevir and St John's Wort
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2012to Dec 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following inclusion criteria within 28 days prior to day 0:
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
- Male or non-pregnant, non-lactating females
- Between 18 to 65 years, inclusive
- Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
- Women of childbearing potential (WOCBP), who are sexually active, must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least one month after the study in addition to the consistent and correct use of a condom. Examples of adequate methods of contraception for females in this trial are diaphragm with spermicide, substance and intra-uterine device. Hormonal contraceptives should not be considered a method of contraception and should be avoided if containing drospirenone.
Show all 9Show fewer
- Willing to consent to their personal details being entered onto The Over volunteering Prevention Scheme (TOPS) database.
- Registered with a GP in the UK
- Willing to bring photo ID to each visit
Who cannot join
- Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
- Any significant acute or chronic medical illness
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
- Positive blood screen for hepatitis B and/or C antibodies
- Positive blood screen for HIV-1 and 2 antibodies
- Current or recent (within three months) gastrointestinal disease
Show all 12Show fewer
- Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
- Exposure to any investigational drug or placebo within three months of first dose of study drug (additional check to be made on TOPS www.tops.org.uk).
- Consumption of grapefruit or Seville oranges, or any grapefruit or Seville orange containing product within one week of first dose of study drug and for the duration of the study
- Use of any other drugs, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs (note OCPs containing drosperinone should be excluded)
- Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 30 days after the end of the treatment period
- Previous allergy to any of the constituents of the pharmaceuticals administered in this trial
Trial locations and contacts
1 site in 1 country.
About this study
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.
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).
Read more
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.
Read the detailed 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.
- Conditions
- Hepatitis C
- Being tested
- Boceprevir, St John's Wort
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BoceprevirDrug
Also called Boceprevir 800 mg three times daily
Boceprevir as Victrelis(r) 200mg capsules
St John's WortDrug
Also called Ucalm (R) tablets, two tablets given once daily
Each Ucalm(r) tablet contains 300mg of St Johns Wort extract
| Study group | Role | What they receive |
|---|---|---|
| St John's Wort, then Boceprevir | Experimental | D 1-14 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 22-35 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 31-35 Boceprevir 800mg tds D 52-56 Boceprevir 800mg tds Receives: Drug: Boceprevir; Drug: St John's Wort |
| Boceprevir, then St John's Wort | Experimental | D 10-14 Boceprevir 800mg tds D 22-35 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 31-35 Boceprevir 800mg tds D 43-56 St. John's Wort 2 x 300mg (Ucalm(r)) QD Receives: Drug: Boceprevir; Drug: St John's Wort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic of Boceprevir in the Presence of Ucalm (St John's Wort)
Pharmacokinetic parameters (maximum and trough concentrations, and area under concentratof boceprevir and SJW will be evaluated when given in combination at steady-state to evaluate possible differences in concentrations during co-administration versus drug given alone.
The pharmacokinetic parameters calculated for boceprevir and SJW will be Ctrough,the maximum observed plasma concentration (Cmax), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve.
All pharmacokinetic parameters will be calculated using non-compartmental modelling techniques (WinNonlin®) and all statistical calculations performed within-participant changes in the assessed pharmacokinetic parameters (drug alone vs drug combination) will be evaluated by calculating geometric mean ratios.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2012 (estimated)
- Study startAug 2012
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- St Stephens Aids Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Liverpool, University of Turin, Italy
- Responsible party
- Sponsor
- Investigators
- Marta Boffito, Principal investigator, HIV Consultant
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01663922
- Sponsor's protocol ID
- SSAT 045
- Status last verified
- Sep 2014
- First submitted
- 3 Aug 2012
- Last updated
- 29 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Jackson A, D'Avolio A, Moyle G, Bonora S, Di Perri G, Else L, Simiele M, Singh GJ, Back D, Boffito M. Pharmacokinetics of the co-administration of boceprevir and St John's wort to male and female healthy volunteers. J Antimicrob Chemother. 2014 Jul;69(7):1911-5. doi: 10.1093/jac/dku060. Epub 2014 Mar 6.
PubMed 24610312
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01663922
- Acronym / sponsor ID
- SSAT 045
- Conditions
- Hepatitis C
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- St Stephens Aids TrustUniversity, hospital or other
- Collaborators
- University of Liverpool, University of Turin, Italy
- Study start
- Aug 2012
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 13 Aug 2012 (estimated)
- Results
- Posted 29 Sep 2014
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 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.
Detailed 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| St John's Wort, then Boceprevir | Experimental | Drug: Boceprevir, Drug: St John's WortD 1-14 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 22-35 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 31-35 Boceprevir 800mg tds D 52-56 Boceprevir 800mg tds |
| Boceprevir, then St John's Wort | Experimental | Drug: Boceprevir, Drug: St John's WortD 10-14 Boceprevir 800mg tds D 22-35 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 31-35 Boceprevir 800mg tds D 43-56 St. John's Wort 2 x 300mg (Ucalm(r)) QD |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
- Male or non-pregnant, non-lactating females
- Between 18 to 65 years, inclusive
- Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
- Women of childbearing potential (WOCBP), who are sexually active, must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least one month after the study in addition to the consistent and correct use of a condom. Examples of adequate methods of contraception for females in this trial are diaphragm with spermicide, substance and intra-uterine device. Hormonal contraceptives should not be considered a method of contraception and should be avoided if containing drospirenone.
Key exclusion criteria (12 listed)
- Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
- Any significant acute or chronic medical illness
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
- Positive blood screen for hepatitis B and/or C antibodies
- Positive blood screen for HIV-1 and 2 antibodies
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 |
|---|---|---|
| BoceprevirAlso: Boceprevir 800 mg three times dailyBoceprevir as Victrelis(r) 200mg capsules | Drug | Boceprevir, then St John's Wort, St John's Wort, then Boceprevir |
| St John's WortAlso: Ucalm (R) tablets, two tablets given once dailyEach Ucalm(r) tablet contains 300mg of St Johns Wort extract | Drug | Boceprevir, then St John's Wort, St John's Wort, then Boceprevir |
Primary outcome
Pharmacokinetic of Boceprevir in the Presence of Ucalm (St John's Wort)
Time frame: 6 months
Pharmacokinetic parameters (maximum and trough concentrations, and area under concentratof boceprevir and SJW will be evaluated when given in combination at steady-state to evaluate possible differences in concentrations during co-administration versus drug given alone. The pharmacokinetic parameters calculated for boceprevir and SJW will be Ctrough,the maximum observed plasma concentration (Cmax), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve. All pharmacokinetic parameters will be calculated using non-compartmental modelling techniques (WinNonlin®) and all statistical calculations performed within-participant changes in the assessed pharmacokinetic parameters (drug alone vs drug combination) will be evaluated by calculating geometric mean ratios.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24610312Jackson A, D'Avolio A, Moyle G, Bonora S, Di Perri G, Else L, Simiele M, Singh GJ, Back D, Boffito M. Pharmacokinetics of the co-administration of boceprevir and St John's wort to male and female healthy volunteers. J Antimicrob Chemother. 2014 Jul;69(7):1911-5. doi: 10.1093/jac/dku060. Epub 2014 Mar 6.
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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.
Marta Boffito principal investigator
HIV Consultant
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 Boceprevir and St John's Wort in people with Hepatitis C, run by St Stephens Aids Trust at 1 site in United Kingdom.
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 9 inclusion and 12 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 29 Sep 2014. 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 Kingdom. 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?
Yes. Results are posted in the registry (first posted 29 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Pharmacokinetic of Boceprevir in the Presence of Ucalm (St John's Wort) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01663922, which also lists 1 linked publication.
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 29 Sep 2014.