Interaction Between Paroxetine and Telaprevir (ROLEX)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Radboud University
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01841502
First received: April 2, 2013
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Hepatitis C Infection
Depression
Drug: Paroxetine
Drug: telaprevir
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 16
Study Start Date: May 2013
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01841502

Contacts
Contact: David Burger, PharmD, PhD +31 24 3616405 d.burger@akf.umcn.nl
Contact: Birgit Jacobs, PharmD +31 24 3616405 b.jacobs@akf.umcn.nl

Locations
Netherlands
GGD Amsterdam Recruiting
Amsterdam, Netherlands
Contact: K Lindenburg, MD         
Principal Investigator: K Lindenburg, MD         
Academic Medical Centre Amsterdam Recruiting
Amsterdam, Netherlands
Contact: M van der Valk, MD, PhD         
Principal Investigator: M van der Valk, MD, PhD         
Sub-Investigator: Reesink, MD         
Reinier de Graaf Groep Not yet recruiting
Delft, Netherlands
Contact: Brouwer, MD, PhD         
Principal Investigator: Brouwer, MD, PhD         
University Medical Centre Groningen Not yet recruiting
Groningen, Netherlands
Contact: van Assen, MD, PhD         
Principal Investigator: van Assen, MD, PhD         
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands
Contact: D Burger, PharmD, PhD         
Sub-Investigator: J Drenth, MD, PhD         
Maasstadziekenhuis Recruiting
Rotterdam, Netherlands
Contact: den Hollander, MD, PhD         
Principal Investigator: den Hollander, MD         
University Medical Centre Utrecht Not yet recruiting
Utrecht, Netherlands
Contact: J Arends, MD. PhD         
Principal Investigator: J Arends, MD, PhD         
Sponsors and Collaborators
Radboud University
Janssen, LP
Investigators
Principal Investigator: David Burger, PharmD, PhD Radboud University
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01841502     History of Changes
Other Study ID Numbers: AKF UMCN 12.02
Study First Received: April 2, 2013
Last Updated: June 20, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
telaprevir
paroxetine
interaction
pharmacokinetics

Additional relevant MeSH terms:
Depression
Depressive Disorder
Hepatitis
Hepatitis A
Hepatitis C
Behavioral Symptoms
Mood Disorders
Mental Disorders
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Paroxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 15, 2014