Study to Evaluate the Influence of Nevirapine to Atazanavir in Steady State Equilibrium in HIV Patients - Full Text View

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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Nevirapine Ritonavir Atazanavir Atazanavir sulfate

U.S. FDA Resources

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:

Atazanavir (Reyataz): capsules 150 mg (2 capsules/24h)

Ritonavir (Norvir): capsules 100 mg (1 capsule/24h)

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 (Adult)
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


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:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Atazanavir Sulfate Nevirapine HIV Protease Inhibitors	Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Cytochrome P-450 CYP3A Inducers Cytochrome P-450 Enzyme Inducers

ClinicalTrials.gov processed this record on September 26, 2016