Interaction Between Paroxetine and Telaprevir (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.
Hepatitis C Infection
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||The ROLE of ParoXetine in Patients Taking Telaprevir-based Hepatitis C Therapy: Lack of a Drug-drug Interaction? (ROLEX)|
- paroxetine area under the curve (AUC) [ Time Frame: day -1 and day 14 ] [ Designated as safety issue: No ]paroxetine AUC will be compared intrasubject: day 14 + telaprevir / day -1 (without telaprevir)
- paroxetine Cmax and C24 [ Time Frame: Day -1 and Day 14 ] [ Designated as safety issue: No ]Comparison of Cmax and C24 of paroxetine intrasubject. Day 14 (+telaprevir) / Day -1 (without telaprevir)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Day -1 to Day 28 ] [ Designated as safety issue: Yes ]Adverse events will be scored during the study
- short term HCV RNA response [ Time Frame: week 4 ] [ Designated as safety issue: No ]At week 4 HCV RNA will be determined
- telaprevir area under the curve (AUC) [ Time Frame: Day 14 ] [ Designated as safety issue: No ]Telaprevir pharmacokinetics (PK) will be determined with paroxetine concomitant use. To be compared to historical data
|Study Start Date:||May 2013|
|Estimated Study Completion Date:||May 2014|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Active Comparator: paroxetine alone
paroxetine 20 mg tablet once daily oral
paroxetine 20 mg once daily
Experimental: paroxetine + telaprevir
paroxetine 20 mg tablet once daily + telaprevir 1125 mg (3 tablets 375mg) twice daily oral
paroxetine 20 mg once dailyDrug: telaprevir
telaprevir 1125 mg twice daily
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.
|Contact: David Burger, PharmD, PhD||+31 24 email@example.com|
|Contact: Birgit Jacobs, PharmD||+31 24 firstname.lastname@example.org|
|Contact: K Lindenburg, MD|
|Principal Investigator: K Lindenburg, MD|
|Academic Medical Centre Amsterdam||Recruiting|
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|Principal Investigator: M van der Valk, MD, PhD|
|Sub-Investigator: Reesink, MD|
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|Principal Investigator: Brouwer, MD, PhD|
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|Contact: van Assen, MD, PhD|
|Principal Investigator: van Assen, MD, PhD|
|Radboud University Nijmegen Medical Centre||Recruiting|
|Contact: D Burger, PharmD, PhD|
|Sub-Investigator: J Drenth, MD, PhD|
|Contact: den Hollander, MD, PhD|
|Principal Investigator: den Hollander, MD|
|University Medical Centre Utrecht||Not yet recruiting|
|Contact: J Arends, MD. PhD|
|Principal Investigator: J Arends, MD, PhD|
|Principal Investigator:||David Burger, PharmD, PhD||Radboud University|