Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

Ritonavir withdrawal, atazanavir 200 mg/12h

Telaprevir interactions

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring Chronic hepatitis C, HIV-infection, Drug interaction

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Hospital Universitario Virgen del Rocio

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Telaprevir interactions

Arm Description

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 Intervention: Ritonavir will be withdrawn and the atazanavir dose increased to 200 mg/12h for days 1 to 7.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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT01818856

First Posted

December 29, 2012

Last Updated

April 19, 2013

Sponsor

Hospitales Universitarios Virgen del Rocío

Collaborators

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01818856

Brief Title

Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2013

Overall Recruitment Status

Completed

Study Start Date

December 2012 (undefined)

Primary Completion Date

April 2013 (Actual)

Study Completion Date

April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Hospitales Universitarios Virgen del Rocío

Collaborators

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C, Chronic, HIV Infection

Keywords

Chronic hepatitis C, HIV-infection, Drug interaction

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Telaprevir interactions

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Ritonavir withdrawal, atazanavir 200 mg/12h

Other Intervention Name(s)

Reyataz, Norvir, Incivo

Intervention Type

Drug

Intervention Name(s)

Telaprevir interactions

Other Intervention Name(s)

Incivo, Reyataz, Norvir

Primary Outcome Measure Information:

Title

Changes in pharmacokinetic parameters of TVR

Description

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.

Time Frame

7 - 10 days

Secondary Outcome Measure Information:

Title

Changes in pharmacokinetic parameters of ATV

Description

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.

Time Frame

7 - 10 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Luis F Lopez-Cortes, MD, PhD.

Organizational Affiliation

Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla. Spain.

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital Universitario Virgen del Rocio

City

Seville

ZIP/Postal Code

41013

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

25801562

Citation

Gutierrez-Valencia A, Ruiz-Valderas R, Ben-Marzouk-Hidalgo OJ, Torres-Cornejo A, Espinosa N, Castillo-Ferrando JR, Viciana P, Lopez-Cortes LF. Telaprevir and ribavirin interaction: higher ribavirin levels are not only due to renal dysfunction during triple therapy. Antimicrob Agents Chemother. 2015;59(6):3257-62. doi: 10.1128/AAC.04795-14. Epub 2015 Mar 23.

Results Reference

derived

PubMed Identifier

24145880

Citation

Gutierrez-Valencia A, Ruiz-Valderas R, Torres-Cornejo A, Viciana P, Espinosa N, Castillo-Ferrando JR, Lopez-Cortes LF. Role of ritonavir in the drug interactions between telaprevir and ritonavir-boosted atazanavir. Clin Infect Dis. 2014 Jan;58(2):268-73. doi: 10.1093/cid/cit693. Epub 2013 Oct 21.

Results Reference

derived

Hepatitis C, Chronic, HIV Infection

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial