ROLEX: Interaction Between Paroxetine and Telaprevir

Sponsor

Radboud University Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT01841502

Collaborator

Janssen, LP (Industry)

Enrollment

Locations

Arms

Duration (Months)

0.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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 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

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

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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 1, 2013

Actual Primary Completion Date :

Sep 1, 2014

Actual Study Completion Date :

Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: paroxetine alone paroxetine 20 mg tablet once daily oral	Drug: Paroxetine paroxetine 20 mg once daily
Experimental: paroxetine + telaprevir paroxetine 20 mg tablet once daily + telaprevir 1125 mg (3 tablets 375mg) twice daily oral	Drug: Paroxetine paroxetine 20 mg once daily Drug: telaprevir telaprevir 1125 mg twice daily

Arm

Intervention/Treatment

Active Comparator: paroxetine alone

paroxetine 20 mg tablet once daily oral

Drug: Paroxetine

paroxetine 20 mg once daily

Experimental: paroxetine + telaprevir

paroxetine 20 mg tablet once daily + telaprevir 1125 mg (3 tablets 375mg) twice daily oral

Drug: Paroxetine

paroxetine 20 mg once daily

Drug: telaprevir

telaprevir 1125 mg twice daily

Outcome Measures

Primary Outcome Measures

paroxetine area under the curve (AUC) [day -1 and day 14]
paroxetine AUC will be compared intrasubject: day 14 + telaprevir / day -1 (without telaprevir)

Secondary Outcome Measures

paroxetine Cmax and C24 [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 [Day -1 to Day 28]
Adverse events will be scored during the study
short term HCV RNA response [week 4]
At week 4 HCV RNA will be determined
telaprevir area under the curve (AUC) [Day 14]
Telaprevir pharmacokinetics (PK) will be determined with paroxetine concomitant use. To be compared to historical data

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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)

Contacts and Locations

Locations

	Site	City	Country
1	Academic Medical Centre Amsterdam	Amsterdam	Netherlands
2	GGD Amsterdam	Amsterdam	Netherlands
3	Reinier de Graaf Groep	Delft	Netherlands
4	University Medical Centre Groningen	Groningen	Netherlands
5	Radboud University Nijmegen Medical Centre	Nijmegen	Netherlands
6	Maasstadziekenhuis	Rotterdam	Netherlands
7	University Medical Centre Utrecht	Utrecht	Netherlands