Interaction Between Paroxetine and Telaprevir (ROLEX)
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|ClinicalTrials.gov Identifier: NCT01841502|
Recruitment Status : Terminated (Telaprevir will not be used in NL, no more inclusions are expected.)
First Posted : April 26, 2013
Last Update Posted : October 28, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Hepatitis C Infection Depression||Drug: Paroxetine Drug: telaprevir||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The ROLE of ParoXetine in Patients Taking Telaprevir-based Hepatitis C Therapy: Lack of a Drug-drug Interaction? (ROLEX)|
|Study Start Date :||May 2013|
|Actual Primary Completion Date :||September 2014|
|Actual Study Completion Date :||September 2014|
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 daily
telaprevir 1125 mg twice daily
- 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)
- paroxetine Cmax and C24 [ Time Frame: Day -1 and Day 14 ]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 ]Adverse events will be scored during the study
- short term HCV RNA response [ Time Frame: week 4 ]At week 4 HCV RNA will be determined
- telaprevir area under the curve (AUC) [ Time Frame: Day 14 ]Telaprevir pharmacokinetics (PK) will be determined with paroxetine concomitant use. To be compared to historical data
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01841502
|Academic Medical Centre Amsterdam|
|Reinier de Graaf Groep|
|University Medical Centre Groningen|
|Radboud University Nijmegen Medical Centre|
|University Medical Centre Utrecht|
|Principal Investigator:||David Burger, PharmD, PhD||Radboud University|