Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir

Study Overview
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Brief Summary
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Hypothesis: the Telaprevir(TVR) plasma levels (750 mg q8h or 1125 mg/12h )will not be affected when co-administered with un-boosted Atazanavir (ATV) 200 mg q12h plus two analogues (NRTIs) in HCV/HIV-co-infected patients.

Detailed Description
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Objectives Primary Outcome Measures: evaluate the changes in the plasma pharmacokinetic parameters (Cmax, Cmin, AUC, t 1/2, and Cl) of Telaprevir (TVR) administered at 750 mg/8h together with un-boosted Atazanavir (200 mg/12h), taking as reference the pharmacokinetic parameters observed when TVR is administered with Atazanavir/ritonavir (300/100 mg/day) To assess the changes in the plasma pharmacokinetic parameters of Atazanavir administered as 200 mg/12h with respect to its administration as 300/100 mg/day when administered together with TVR (750 mg/8h or 1125 mh/12h). Method: open labelled clinical trial with a planned duration of 24 weeks in which 14 HIV/Hepatitis C virus genotype 1 patients under treatment with pegylated α-interferon, Ribavirin and Telaprevir will be enrolled. A 24 hours pharmacokinetic profile will be obtained after a supervised drug intake while taking TVR and ATV/rtv. Afterwards, the patients will take un-boosted ATV 200 mg bid for 7 - 10 days. Subsequently, a new pharmacokinetic profile will be obtained.

Official Title
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Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir in HIV/HCV-co-infected Patients Under Treatment for Genotype 1 Chronic Hepatitis C.

Conditions
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Hepatitis C, Chronic, HIV Infection

Intervention / Treatment
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* Drug: Ritonavir withdrawal, atazanavir 200 mg/12h
* Drug: Telaprevir interactions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years old co-infected with HIV and genotype 1 HCV under treatment with pegylated α-interferon, Ribavirin and Telaprevir according to the recommendations of the Spanish Agency of Medicines and Health Products. Informed consent of the patient. Exclusion Criteria: The usual exclusion criteria in clinical practice to start the treatment with these drugs (pegylated α-interferon, Ribavirin, Telaprevir and atazanavir) according to the Spanish and international recommendations (Spanish Agency of Medicines and Health Products,European Association for the Study of the Liver Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2011. Consensus Document of Gesida/Spanish Plan on Aids regarding the antiretroviral treatment in adults infected with the human immunodeficiency virus [Updated January 2012]). Concomitant use of drugs or medicinal products that could alter the pharmacokinetics of TVR or ATV. Medical records suggesting malabsorption or presence of diarrhea (>3 depositions/day) that could interfere with the absorption of the studied drugs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telaprevir interactions<br>Telaprevir 750 mg/8h or 1125 mg/12h (+ pegIFN alfa and ribavirin) plus Atazanavir/ritonavir 300/100 mg/24. Pharmacokinetic profile on day 0. Intervention: Ritonavir will be withdrawn and the atazanavir dose increased to 200 mg/12h for days 1 to 7. On day 8: a morning dose of Telaprevir (750 mg or 1125 mg) plus Atazanavir 200 mg. Pharmacokinetic profile for 12 hours | Drug: Ritonavir withdrawal, atazanavir 200 mg/12h<br> <br> * Other names: Incivo;Drug: Telaprevir interactions<br> <br> * Other names: Norvir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in pharmacokinetic parameters of TVR | The Telaprevir peak concentrations (Cmax), trough levels (Cmin) at 8 or 12 hours, the areas under the curves over the dosing interval (AUC0-τ), and half-life during the elimination phase (t½ β) will be compared between days 0 and 7 as geometric mean ratios (GMRs) and their 90% CIs using day 0 values as reference. The differences in pharmacokinetic parameters between the regimens will be considered significant when the interval between low and high 90% CI did not include the value 1.0. | 7 - 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in pharmacokinetic parameters of ATV | The Atazanavir peak concentrations (Cmax), trough levels (Cmin) at 12 or 24 hours, the areas under the curves over the dosing interval (AUC0-τ), and half-life during the elimination phase (t½ β) will be summarized as geometric means (GM) and will be compared between days 0 and 7 as geometric mean ratios (GMRs) and their 90% CIs using day 0 values as reference. The differences in pharmacokinetic parameters between the regimens will be considered significant when the interval between low and high 90% CI did not include the value 1.0. | 7 - 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic hepatitis C, HIV-infection, Drug interaction