Hepatitis C InfectionPhase 2ROLEXNCT01841502
Interaction Between Paroxetine and Telaprevir
A Phase 2 study testing Paroxetine and telaprevir in people with Hepatitis C Infection and Depression, run by Radboud University Medical Center at 7 sites in Netherlands.
Trial summary
Hepatitis C (HCV) infected patients are often in need for an antidepressant. The introduction of Direct Acting Antivirals such as telaprevir has greatly improved treatment outcome of HCV infected patients.Telaprevir has been studied with one antidepressant, escitalopram: plasma concentrations of the antidepressant… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C Infection, Depression
- What is being tested?
- Paroxetine and telaprevir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 7 sitesNetherlands
- Study dates
- May 2013to Sep 2014
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is at least 18 and not older than 65 years at screening.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- Subject has a chronic HCV infection with genotype 1.
- Subject is eligible for telaprevir containing HCV treatment.
- Subject is on a stable dose of 20 mg paroxetine once daily for at least 4 weeks.
Who cannot join
- Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- Pregnant female (as confirmed by a human chorionic gonadotropin (HCG) test performed less than 6 weeks before Day -1) or breast-feeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout.
- Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- Inability to understand the nature and extent of the trial and the procedures required.
- Participation in a drug trial within 60 days prior to the first dose of telaprevir.
- Use of relevant concomitant medication, as assessed by a hospital pharmacist (member of the study team).
- Hemoglobin < 12 g/dL (females) or < 13 g/dL (males) (7.4 respectively 8.0 mM).
- Poor- or ultrarapid metabolizer CYP2D6 (based on genetic testing)
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Netherlands7 sites
Academic Medical Centre Amsterdam
Amsterdam
GGD Amsterdam
Amsterdam
Reinier de Graaf Groep
Delft
University Medical Centre Groningen
Groningen
Radboud University Nijmegen Medical Centre
Nijmegen
Maasstadziekenhuis
Rotterdam
University Medical Centre Utrecht
Utrecht
About this study
Official title: The ROLE of ParoXetine in Patients Taking Telaprevir-based Hepatitis C Therapy: Lack of a Drug-drug Interaction? (ROLEX)
Hepatitis C (HCV) infected patients are often in need for an antidepressant. The introduction of Direct Acting Antivirals such as telaprevir has greatly improved treatment outcome of HCV infected patients.Telaprevir has been studied with one antidepressant, escitalopram: plasma concentrations of the antidepressant were reduced by 35% and without dose adjustment this may lead to inadequate treatment of depressive symptoms. There is a need for more data on telaprevir drug interactions with other antidepressants.
For a number of reasons, paroxetine may be a good candidate for use together with telaprevir-containing HCV treatment.
The interaction between paroxetine and telaprevir has not been studied before.
Read the detailed description
HCV infected patients are often in need for an antidepressant. Inadequate treatment of depression during HCV treatment has a negative effect on adherence to HCV treatment, with suboptimal response as a potential result.
The introduction of Direct Acting Antivirals such as telaprevir has greatly improved treatment outcome of HCV infected patients. Telaprevir, however, causes some significant drug-drug interactions and hence co-administration of other medications should preferably only be done based on clinical evidence that such a combination is safe.
Telaprevir has been studied with one antidepressant, escitalopram: plasma concentrations of the antidepressant were reduced by 35% and without dose adjustment this may lead to inadequate treatment of depressive symptoms. Dose titration of escitalopram may be needed but it may take several weeks before a patient has reached a therapeutic dose.
There is a need for more data on telaprevir drug interactions with other antidepressants. First, the data above show that a negative interaction occurs with escitalopram and dose-titration of the antidepressant may take too long to prevent the (re-)occurrence of depressive symptoms. Second, not all patients benefit from escitalopram and those with (prior) treatment failure on escitalopram may require an alternative agent. Third, although escitalopram is generally well-tolerated, side effects may occur and necessitate treatment discontinuation. Finally, especially in the previous intravenous drug users on methadone, escitalopram might not be the antidepressant of choice, since escitalopram as well as methadone are drugs that can lead to QTc interval prolongation and have a risk of Torsades de Pointes.
For a number of reasons, paroxetine may be a good candidate for use together with telaprevir-containing HCV treatment. First, paroxetine has been shown to prevent depressive symptoms in patients initiating HCV treatment with elevated depressive symptoms at baseline. Second, paroxetine is an inhibitor of and is metabolized by CYP2D6 while telaprevir is an inhibitor of and is metabolized by CYP3A, and therefore no drug-drug interaction is expected. Third, paroxetine is one of the most widely prescribed antidepressants with a well-established efficacy and safety profile.
- Conditions
- Hepatitis C Infection, Depression
- Being tested
- Paroxetine, telaprevir
- Keywords
- telaprevir, paroxetine, interaction, pharmacokinetics
- Medical subject headings
- Hepatitis C, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParoxetineDrug
paroxetine 20 mg once daily
telaprevirDrug
telaprevir 1125 mg twice daily
| Study group | Role | What they receive |
|---|---|---|
| paroxetine alone | Active comparator | paroxetine 20 mg tablet once daily oral Receives: Drug: Paroxetine |
| paroxetine + telaprevir | Experimental | paroxetine 20 mg tablet once daily + telaprevir 1125 mg (3 tablets 375mg) twice daily oral Receives: Drug: Paroxetine; Drug: telaprevir |
What is being measured
The primary outcome is the main question the study is designed to answer.
paroxetine area under the curve (AUC)
paroxetine AUC will be compared intrasubject: day 14 + telaprevir / day -1 (without telaprevir)
Measured: day -1 and day 14
Secondary outcomes (4)
paroxetine Cmax and C24
Comparison of Cmax and C24 of paroxetine intrasubject. Day 14 (+telaprevir) / Day -1 (without telaprevir)
Measured: Day -1 and Day 14
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Adverse events will be scored during the study
Measured: Day -1 to Day 28
short term HCV RNA response
At week 4 HCV RNA will be determined
Measured: week 4
telaprevir area under the curve (AUC)
Telaprevir pharmacokinetics (PK) will be determined with paroxetine concomitant use. To be compared to historical data
Measured: Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2013 (estimated)
- Study startMay 2013
- Primary completionSep 2014
- Study completionSep 2014
Why it stopped: Telaprevir will not be used in NL, no more inclusions are expected.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis C InfectionStudies 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 2
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen, LP
- Responsible party
- Sponsor
- Investigators
- David Burger, PharmD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01841502
- Sponsor's protocol ID
- AKF UMCN 12.02
- Acronym
- ROLEX
- Status last verified
- Dec 2020
- First submitted
- 2 Apr 2013
- Last updated
- 8 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The ROLE of ParoXetine in Patients Taking Telaprevir-based Hepatitis C Therapy: Lack of a Drug-drug Interaction? (ROLEX)
- ClinicalTrials.gov ID
- NCT01841502
- Acronym / sponsor ID
- ROLEX / AKF UMCN 12.02
- Conditions
- Hepatitis C Infection, Depression
- Keywords
- telaprevir, paroxetine, interaction, pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Telaprevir will not be used in NL, no more inclusions are expected.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Janssen, LP
- Study start
- May 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 26 Apr 2013 (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.
Hepatitis C (HCV) infected patients are often in need for an antidepressant. The introduction of Direct Acting Antivirals such as telaprevir has greatly improved treatment outcome of HCV infected patients.Telaprevir has been studied with one antidepressant, escitalopram: plasma concentrations of the antidepressant were reduced by 35% and without dose adjustment this may lead to inadequate treatment of depressive symptoms. There is a need for more data on telaprevir drug interactions with other antidepressants.
For a number of reasons, paroxetine may be a good candidate for use together with telaprevir-containing HCV treatment.
The interaction between paroxetine and telaprevir has not been studied before.
Detailed description
HCV infected patients are often in need for an antidepressant. Inadequate treatment of depression during HCV treatment has a negative effect on adherence to HCV treatment, with suboptimal response as a potential result.
The introduction of Direct Acting Antivirals such as telaprevir has greatly improved treatment outcome of HCV infected patients. Telaprevir, however, causes some significant drug-drug interactions and hence co-administration of other medications should preferably only be done based on clinical evidence that such a combination is safe.
Telaprevir has been studied with one antidepressant, escitalopram: plasma concentrations of the antidepressant were reduced by 35% and without dose adjustment this may lead to inadequate treatment of depressive symptoms. Dose titration of escitalopram may be needed but it may take several weeks before a patient has reached a therapeutic dose.
There is a need for more data on telaprevir drug interactions with other antidepressants. First, the data above show that a negative interaction occurs with escitalopram and dose-titration of the antidepressant may take too long to prevent the (re-)occurrence of depressive symptoms. Second, not all patients benefit from escitalopram and those with (prior) treatment failure on escitalopram may require an alternative agent. Third, although escitalopram is generally well-tolerated, side effects may occur and necessitate treatment discontinuation. Finally, especially in the previous intravenous drug users on methadone, escitalopram might not be the antidepressant of choice, since escitalopram as well as methadone are drugs that can lead to QTc interval prolongation and have a risk of Torsades de Pointes.
For a number of reasons, paroxetine may be a good candidate for use together with telaprevir-containing HCV treatment. First, paroxetine has been shown to prevent depressive symptoms in patients initiating HCV treatment with elevated depressive symptoms at baseline. Second, paroxetine is an inhibitor of and is metabolized by CYP2D6 while telaprevir is an inhibitor of and is metabolized by CYP3A, and therefore no drug-drug interaction is expected. Third, paroxetine is one of the most widely prescribed antidepressants with a well-established efficacy and safety profile.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| paroxetine alone | Active comparator | Drug: Paroxetineparoxetine 20 mg tablet once daily oral |
| paroxetine + telaprevir | Experimental | Drug: Paroxetine, Drug: telaprevirparoxetine 20 mg tablet once daily + telaprevir 1125 mg (3 tablets 375mg) twice daily oral |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject is at least 18 and not older than 65 years at screening.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- Subject has a chronic HCV infection with genotype 1.
- Subject is eligible for telaprevir containing HCV treatment.
- Subject is on a stable dose of 20 mg paroxetine once daily for at least 4 weeks.
Key exclusion criteria (8 listed)
- Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- Pregnant female (as confirmed by a human chorionic gonadotropin (HCG) test performed less than 6 weeks before Day -1) or breast-feeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout.
- Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- Inability to understand the nature and extent of the trial and the procedures required.
- Participation in a drug trial within 60 days prior to the first dose of telaprevir.
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 |
|---|---|---|
| Paroxetineparoxetine 20 mg once daily | Drug | paroxetine + telaprevir, paroxetine alone |
| telaprevirtelaprevir 1125 mg twice daily | Drug | paroxetine + telaprevir |
Primary outcome
paroxetine area under the curve (AUC)
Time frame: day -1 and day 14
paroxetine AUC will be compared intrasubject: day 14 + telaprevir / day -1 (without telaprevir)
4 secondary outcomes
paroxetine Cmax and C24
Time frame: Day -1 and Day 14
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: Day -1 to Day 28
short term HCV RNA response
Time frame: week 4
telaprevir area under the curve (AUC)
Time frame: Day 14
Results and safety
The study was stopped early (reason given: Telaprevir will not be used in NL, no more inclusions are expected.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
- dissertation page 185-192Link provided by the sponsor.
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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.
David Burger, PharmD, PhD principal investigator
Radboud University Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paroxetine and telaprevir in people with Hepatitis C Infection and Depression, run by Radboud University Medical Center at 7 sites in Netherlands.
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 5 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: stopped early, as of the sponsor's last update on 8 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Telaprevir will not be used in NL, no more inclusions are expected.). Results are not available in the source record.
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?
paroxetine area under the curve (AUC) (time frame: day -1 and day 14). 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 8 Dec 2020.