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

Clinical Pilot Trial to Evaluate the Influence of Nevirapine in Exposure to Atazanavir in Steady State Equilibrium in HIV-infected Adult Patients.

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Atazanavir (Reyataz); Drug: Ritonavir (Norvir); Drug: Nevirapine (Viramune)

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

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
    • Calella, Barcelona, Spain, 08370
      • Hospital Sant Jaume de Calella

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nevirapine-atazanavir; Atazanavir/ritonavir 300/100 mg once daily for ≥2 weeks. Nevirapine was added at a dose of 200 mg once daily from days 0 to 14, and 200 mg twice daily from days 14 to 28.	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*)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint of the study will be the atazanavir plasma concentration	at baseline and week 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with atazanavir plasma concentrations < 0.15 mg/L	at baseline and week 4
Proportion of patients with nevirapine plasma concentrations > 6.0 mg/L	at baseline and week 4
Incidence of adverse events and anomalies in the laboratory tests (haemogram, AST / ALT / FA / GGT, bilirubin, creatinine, urea).	during the 8 weeks of follow-up

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital
• Collaborators: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; Hospital San Jaime de Calella
• Investigators: 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

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: July 24, 2006
• First Submitted That Met QC Criteria: July 24, 2006
• First Posted (Estimate): July 25, 2006

Study Record Updates

• Last Update Posted (Actual): December 4, 2019
• Last Update Submitted That Met QC Criteria: December 3, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Nevirapine; Pharmacokinetics; Atazanavir; Interactions
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Nevirapine; Ritonavir; Atazanavir Sulfate
• Other Study ID Numbers: NEVIATAZ; 2006-001140-31