Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Luis F. Lopez-Cortes, Hospitales Universitarios Virgen del Rocío
ClinicalTrials.gov Identifier:
NCT01818856
First received: December 29, 2012
Last updated: April 19, 2013
Last verified: April 2013

December 29, 2012
April 19, 2013
December 2012
April 2013   (final data collection date for primary outcome measure)
Changes in pharmacokinetic parameters of TVR [ Time Frame: 7 - 10 days ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01818856 on ClinicalTrials.gov Archive Site
Changes in pharmacokinetic parameters of ATV [ Time Frame: 7 - 10 days ] [ Designated as safety issue: No ]
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.
Same as current
Not Provided
Not Provided
 
Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir
Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir in HIV/HCV-co-infected Patients Under Treatment for Genotype 1 Chronic Hepatitis C.

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.

Objectives

  1. 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)
  2. 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.

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis C, Chronic
  • HIV Infection
  • Drug: Ritonavir withdrawal, atazanavir 200 mg/12h
    Other Names:
    • Reyataz
    • Norvir
    • Incivo
  • Drug: Telaprevir interactions
    Other Names:
    • Incivo
    • Reyataz
    • Norvir
Experimental: Telaprevir interactions

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

Interventions:
  • Drug: Ritonavir withdrawal, atazanavir 200 mg/12h
  • Drug: Telaprevir interactions
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
April 2013
April 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01818856
LLC-TEL-2012-1, 2012-002515-25
Yes
Luis F. Lopez-Cortes, Hospitales Universitarios Virgen del Rocío
Hospitales Universitarios Virgen del Rocío
Bristol-Myers Squibb
Principal Investigator: Luis F Lopez-Cortes, MD, PhD. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla. Spain.
Hospitales Universitarios Virgen del Rocío
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP