- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01841502
Interaction Between Paroxetine and Telaprevir (ROLEX)
The ROLE of ParoXetine in Patients Taking Telaprevir-based Hepatitis C Therapy: Lack of a Drug-drug Interaction? (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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Amsterdam, Netherlands
- Academic Medical Centre Amsterdam
-
Amsterdam, Netherlands
- GGD Amsterdam
-
Delft, Netherlands
- Reinier de Graaf Groep
-
Groningen, Netherlands
- University Medical Centre Groningen
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Nijmegen, Netherlands
- Radboud University Nijmegen Medical Centre
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Rotterdam, Netherlands
- Maasstadziekenhuis
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Utrecht, Netherlands
- University Medical Centre Utrecht
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
day -1 and day 14
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
Day -1 and Day 14
|
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
|
Day -1 to Day 28
|
short term HCV RNA response
Time Frame: week 4
|
At week 4 HCV RNA will be determined
|
week 4
|
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
|
Day 14
|
Collaborators and Investigators
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Hepatitis
- Hepatitis C
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antidepressive Agents, Second-Generation
- Cytochrome P-450 CYP2D6 Inhibitors
- Paroxetine
Other Study ID Numbers
- AKF UMCN 12.02
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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