Study to Evaluate the Influence of Nevirapine to Atazanavir in Steady State Equilibrium in HIV Patients

This study has been completed.
Sponsor:
Collaborators:
Fundacio Lluita Contra la SIDA
Hospital San Jaime de Calella
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00355719
First received: July 24, 2006
Last updated: June 16, 2009
Last verified: June 2009
  Purpose

The purpose of this study is to evaluate the influence of nevirapine in exposure to atazanavir boosted with ritonavir, in steady state equilibrium, in HIV-infected adult patients.


Condition Intervention Phase
HIV Infections
Drug: Atazanavir (Reyataz)
Drug: Ritonavir (Norvir)
Drug: Nevirapine (Viramune)
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Pilot Trial to Evaluate the Influence of Nevirapine in Exposure to Atazanavir in Steady State Equilibrium in HIV-Infected Adult Patients.

Resource links provided by NLM:


Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • The primary endpoint of the study will be the atazanavir plasma concentration [ Time Frame: at baseline and week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with atazanavir plasma concentrations < 0.15 mg/L [ Time Frame: at baseline and week 4 ] [ Designated as safety issue: No ]
  • Proportion of patients with nevirapine plasma concentrations > 6.0 mg/L [ Time Frame: at baseline and week 4 ] [ Designated as safety issue: No ]
  • Incidence of adverse events and anomalies in the laboratory tests (haemogram, AST / ALT / FA / GGT, bilirubin, creatinine, urea). [ Time Frame: during the 8 weeks of follow-up ] [ Designated as safety issue: Yes ]

Enrollment: 14
Study Start Date: January 2007
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Atazanavir (Reyataz)
    Atazanavir (Reyataz): capsules 150 mg (2 capsules/24h)
    Drug: Ritonavir (Norvir)
    Ritonavir (Norvir): capsules 100 mg (1 capsule/24h)
    Drug: Nevirapine (Viramune)
    Nevirapine (Viramune): tablets 200 mg (1 tablet/12h*)
Detailed Description:

In recent years, new treatment strategies have appeared aimed at reducing the risk of treatment-derived toxicity without compromising efficacy.

Of the recent antiretroviral drugs, atazanavir is a protease inhibitor (PI) whose pharmacokinetic profile allows it to be given in a single daily take with a scant impact on lipid metabolism. This second characteristic makes atazanavir a good alternative for patients with a high vascular risk. However, one of its drawbacks is that it may present clinically relevant interactions with other drugs.

Another antiretroviral agent with a scant impact on lipid metabolism is nevirapine. Different studies have described an improvement in lipid profile, as well as a less atherogenic tendency in patients treated with nevirapine. Moreover, the combination of nevirapine with PI drugs in the context of nucleoside-sparing strategies may permit a suitable control of viral replication, and an improvement in the mitochondrial toxicity derived from treatment with NTRI, which may possibly result in a minor incidence or in a clinical improvement of lipodystrophy.

The combination of atazanavir with nevirapine may be of major interest in HIV-infected patients that have had a cardiovascular event (secondary prevention) or are at a high risk of having one (primary prevention). Similarly, this combination of drugs may be promising as a nucleoside-sparing strategy. However, according to preliminary data, the joint administration of nevirapine with atazanavir may lead to a reduction in the atazanavir plasma concentration. Thus, before evaluating the clinical utility of this combination of drugs, pharmacokinetic studies evaluating the existence of significant pharmacokinetic interactions between both are necessary

  Eligibility

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

Inclusion Criteria:

  • Age >=18 years.
  • Patients infected by HIV-1 (at least one documented positive Western-Blot).
  • Stable antiretroviral treatment with atazanavir boosted with ritonavir (300/100 mg QD) for at least 14 days.
  • Absence of acute infections and/or tumours in the three months prior to inclusion.
  • Subject able to follow the treatment period.
  • Transaminase values (AST/ALT) below 5 times the upper limit of the interval of normality.
  • In women, negative pregnancy test or not of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or undertaking to use a barrier contraceptive method during the study.
  • Signature of the informed consent.
  • Undetectable viral load.

Exclusion Criteria:

  • Failure to comply with any of the inclusion criteria.
  • Record of allergic hypersensitivity or intolerance to the investigational medication.
  • Any clinical or historic observation that might interfere in the pharmacokinetics of the medication, such as gastrointestinal diseases or surgery (except herniotomy or appendectomy), alterations in the composition of plasma proteins, any indication of hepatic or renal dysfunction.
  • Patients that have been given tenofovir, omeprazole or other proton pump inhibitors or any other medication with relevant interactions with atazanavir within the two weeks prior to the screening visit.
  • Active consumption of alcohol (> 50 g/day) or illegal drugs (except cannabis).
  • Suspicion of unsuitable antiretroviral treatment compliance.
  • Pregnancy or breastfeeding.
  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: NCT00355719

Locations
Spain
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital Sant Jaume de Calella
Calella, Barcelona, Spain, 08370
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
Hospital San Jaime de Calella
Investigators
Principal Investigator: Bonaventura Clotet, MD,PhD LLuita contra la Sida Foundation-HIV Unit
Principal Investigator: Jose Molto, MD,PhD LLuita contra la Sida Foundation-HIV Unitat
Principal Investigator: Josep Mª LLibre, MD,PhD Lluita contra la Sida Foundation- HIV Unit
Principal Investigator: Sílvia Valero Hospital Sant Jaume de Calella
  More Information

No publications provided

Responsible Party: LLuita Sida Foundation
ClinicalTrials.gov Identifier: NCT00355719     History of Changes
Other Study ID Numbers: NEVIATAZ, 2006-001140-31
Study First Received: July 24, 2006
Last Updated: June 16, 2009
Health Authority: Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:
Nevirapine
Atazanavir
Pharmacokinetics
Interactions

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Atazanavir
Nevirapine
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014