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

• ClinicalTrials.gov Identifier: NCT00355719
• Recruitment Status: Completed
• First Posted: July 25, 2006
• Last Update Posted: December 4, 2019
• 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
• Information provided by (Responsible Party): Germans Trias i Pujol Hospital

Tracking Information

• First Submitted Date: July 24, 2006
• First Posted Date: July 25, 2006
• Last Update Posted Date: December 4, 2019
• Study Start Date: January 2007
• Actual Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 8, 2007): The primary endpoint of the study will be the atazanavir plasma concentration [ Time Frame: at baseline and week 4 ]
• Original Primary Outcome Measures (submitted: July 24, 2006): The primary endpoint of the study will be the atazanavir plasma concentration

Current Secondary Outcome Measures (submitted: June 16, 2009)

• Proportion of patients with atazanavir plasma concentrations < 0.15 mg/L [ Time Frame: at baseline and week 4 ]
• Proportion of patients with nevirapine plasma concentrations > 6.0 mg/L [ Time Frame: at baseline and week 4 ]
• 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 ]

Original Secondary Outcome Measures (submitted: July 24, 2006)

• Proportion of patients with atazanavir plasma concentrations < 0.15 mg/L
• Proportion of patients with atazanavir plasma concentrations > 3.4 mg/L
• Incidence of adverse events and anomalies in the laboratory tests (haemogram, AST / ALT / FA / GGT, bilirubin, creatinine, urea).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Influence of Nevirapine to Atazanavir in Steady State Equilibrium in HIV Patients
• Official Title: Clinical Pilot Trial to Evaluate the Influence of Nevirapine in Exposure to Atazanavir in Steady State Equilibrium in HIV-infected Adult Patients.
• Brief Summary: 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.

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
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infections

Intervention

• 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*)

Study Arms

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.

Interventions:

• Drug: Atazanavir (Reyataz)
• Drug: Ritonavir (Norvir)
• Drug: Nevirapine (Viramune)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 6, 2008): 14
• Original Enrollment (submitted: July 24, 2006): 15
• Actual Study Completion Date: February 2008
• Actual Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT00355719
• Other Study ID Numbers: NEVIATAZ; 2006-001140-31
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Germans Trias i Pujol Hospital
• Study 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: 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

• PRS Account: Germans Trias i Pujol Hospital
• Verification Date: December 2019