Interaction Between Paroxetine and Telaprevir

NCT ID: NCT01841502

Last Updated: 2020-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-31

Study Completion Date

2014-09-30

Brief Summary

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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

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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

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Hepatitis C Infection Depression

Keywords

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telaprevir paroxetine interaction pharmacokinetics

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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paroxetine alone

paroxetine 20 mg tablet once daily oral

Group Type ACTIVE_COMPARATOR

Paroxetine

Intervention Type DRUG

paroxetine 20 mg once daily

paroxetine + telaprevir

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

Group Type EXPERIMENTAL

Paroxetine

Intervention Type DRUG

paroxetine 20 mg once daily

telaprevir

Intervention Type DRUG

telaprevir 1125 mg twice daily

Interventions

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Paroxetine

paroxetine 20 mg once daily

Intervention Type DRUG

telaprevir

telaprevir 1125 mg twice daily

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen, LP

INDUSTRY

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Burger, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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Academic Medical Centre Amsterdam

Amsterdam, , Netherlands

Site Status

GGD Amsterdam

Amsterdam, , Netherlands

Site Status

Reinier de Graaf Groep

Delft, , Netherlands

Site Status

University Medical Centre Groningen

Groningen, , Netherlands

Site Status

Radboud University Nijmegen Medical Centre

Nijmegen, , Netherlands

Site Status

Maasstadziekenhuis

Rotterdam, , Netherlands

Site Status

University Medical Centre Utrecht

Utrecht, , Netherlands

Site Status

Countries

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Netherlands

Related Links

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Other Identifiers

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AKF UMCN 12.02

Identifier Type: -

Identifier Source: org_study_id