Nevirapine or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir in Human Immunodeficiency Virus (HIV)-1-infected Treatment Naive Adults

NCT00389207 | Completed Phase 3 Results

• 2 other identifiers: 1100.14702005-004330-40
• Study Type: interventional
• Target: 576
• Locations: 10 countries
• Sites: 68

Brief Summary

Primary purpose of this study is to compare the efficacy and safety of two different nevirapine (Viramune) dosing regimens (once daily (QD) and twice daily (BID) application) and of atazanavir/ritonavir (Reyataz/Norvir), all on an emtricitabine/tenofovir disoproxil fumarate (DF) (Truvada) background. Patients will receive either nevirapine (NVP) 200 mg twice daily, or NVP 400 mg once daily , or ritonavir-boosted atazanavir (ATZ/r), all in combination with emtricitabine (FTC) and tenofovir DF (TDF). All patients receiving NVP will start at 200 mg once daily for 2 weeks, because it has been demonstrated that this lead-in dosing regimen reduces the frequency of NVP-induced rash. At Visit 3 (Week 2), patients increase the NVP dose to either 200 mg twice daily or to 400 mg once daily. Patients receiving ATZ/r will be treated with ATZ 300 mg once daily, boosted by 100 mg ritonavir (RTV) once daily. Background antiretroviral therapy for all patients consists of one tablet of Truvada. Treatment duration is 48 weeks (primary endpoint) with an extension to 144 weeks. Patients may also participate in the metabolic sub-study, comparing NVP and ATZ/r for signs and symptoms of lipodystrophy and serum lipid/glycaemic abnormalities.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Treatment Response at Week 48

  Treatment response is defined as a viral load (VL) \<50 copies/mL measured at two consecutive visits prior to Week 48 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 48.

  From baseline to Week 48

Secondary Outcomes (33)

• Treatment Response at Week 48 (TLOVR Algorithm)

  From baseline to Week 48

• Proportion of Patients With VL < 50 Copies/ml

  From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT

• Proportion of Patients With VL < 400 Copies/ml

  From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT

• Change in CD4+ Count From Baseline

  From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT

• Change in Framingham Score From Baseline

  From baseline to Weeks 48, 96 and 144/EOT

Study Arms (3)

NVP bid

ACTIVE COMPARATOR

nevirapine (NVP) 200 mg BID in combination with emtricitabine (FTC) and tenofovir DF (TDF)

Drug: nevirapine bid

NVP qd

EXPERIMENTAL

nevirapine (NVP) 400 mg QD in combination with emtricitabine (FTC) and tenofovir DF (TDF)

Drug: nevirapine qd

ATZ/r

ACTIVE COMPARATOR

ritonavir-boosted atazanavir in combination with emtricitabine (FTC) and tenofovir DF (TDF)

Drug: atazanavir

Interventions

nevirapine bid DRUG

nevirapine twice daily

NVP bid

nevirapine qd DRUG

nevirapine once daily

NVP qd

atazanavir DRUG

atazanavir once daily

ATZ/r

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent in accordance with Good Clinical Practice (GCP) and local regulatory requirements prior to trial participation
• HIV-1-infected males or females \>= 18 years of age with positive serology confirmed by Western blot
• No previous antiretroviral treatment (of more than 7 days)
• Males with CD4+ counts of \< 400 cells/mm3 and females with CD4+ counts of \< 250 cells/mm3
• NVP- and ATZ/r susceptibility based on HIV-1 genotypic resistance report
• Adequate renal function defined as a calculated creatinine clearance (CLCr) \>= 50 ml/min according to the Cockcroft-Gault formula
• Karnofsky score \>= 70
• Acceptable medical history, as assessed by the investigator

You may not qualify if:

• Active drug abuse or chronic alcoholism at the investigator's discretion
• Hepatic cirrhosis stage Child-Pugh B or C
• Female patients of child-bearing potential who:
• have a positive serum pregnancy test at screening or during the study,
• are breast feeding,
• are planning to become pregnant,
• are not willing to use a barrier method of contraception, or are not willing to use methods of contraception other than ethinyl estradiol containing oral contraceptives
• Laboratory parameters Division of Acquired Immunodeficiency Syndrome (DAIDS) \> grade 2 (triglycerides \> DAIDS grade 3; total cholesterol no restrictions)
• Active hepatitis B or C disease, defined as HBsAg-positive or Hepatitis C-Virus-Ribo Nucleic Acid (HCV-RNA)- positive with Aspartate Transaminase/Alanine Transaminase (AST/ALT) \> 2.5x Upper Limit of Normal (ULN) (DAIDS grade 1)
• Hypersensitivity to any ingredients of the test products
• Have therapy with nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cisplatin, pentamidine, tacrolimus, cyclosporine) or potential competitors of renal excretion (e.g., cidofovir, acyclovir, valacyclovir, ganciclovir, valganciclovir, probenecid, high-dose non-steroidal anti-inflammatory drugs (i.e., ibuprofen)) within 3 months prior to study screening or are expected to receive these during the study
• Patients who are receiving other concomitant treatments which are not permitted
• Use of other investigational medications within 30 days before study entry or during the trial
• Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2, chronic treatment with prednisone)
• Patients with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (68)

1100.1470.54004 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1100.1470.54002 Boehringer Ingelheim Investigational Site

Córdoba, Argentina

Location

1100.1470.54003 Boehringer Ingelheim Investigational Site

Mar del Plata, Argentina

Location

1100.1470.54001 Boehringer Ingelheim Investigational Site

Rosario, Argentina

Location

1100.1470.49001 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1100.1470.49002 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1100.1470.49003 Boehringer Ingelheim Investigational Site

Bochum, Germany

Location

1100.1470.49018 Boehringer Ingelheim Investigational Site

Bonn, Germany

Location

1100.1470.49014 Boehringer Ingelheim Investigational Site

Düsseldorf, Germany

Location

1100.1470.49008 Boehringer Ingelheim Investigational Site

Erlangen, Germany

Location

1100.1470.49035 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

1100.1470.49036 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

1100.1470.49033 Boehringer Ingelheim Investigational Site

Freiburg/Breisgau, Germany

Location

1100.1470.49016 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1100.1470.49031 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1100.1470.49037 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1100.1470.49020 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1100.1470.49038 Boehringer Ingelheim Investigational Site

Magdeburg, Germany

Location

1100.1470.49034 Boehringer Ingelheim Investigational Site

München, Germany

Location

1100.1470.49000 Boehringer Ingelheim Investigational Site

Ulm, Germany

Location

1100.1470.49032 Boehringer Ingelheim Investigational Site

Würzburg, Germany

Location

1100.1470.39001 Boehringer Ingelheim Investigational Site

Bergamo, Italy

Location

1100.1470.39003 Boehringer Ingelheim Investigational Site

Bologna, Italy

Location

1100.1470.39012 Ospedale Sant'Anna

Como, Italy

Location

1100.1470.39006 Boehringer Ingelheim Investigational Site

Ferrara, Italy

Location

1100.1470.39010 Boehringer Ingelheim Investigational Site

Lecco, Italy

Location

1100.1470.39004 Boehringer Ingelheim Investigational Site

Torino, Italy

Location

1100.1470.39009 Boehringer Ingelheim Investigational Site

Torrette Di Ancona, Italy

Location

1100.1470.39007 Boehringer Ingelheim Investigational Site

Varese, Italy

Location

1100.1470.55006 Boehringer Ingelheim Investigational Site

Aguascalientes, Mexico

Location

1100.1470.55004 Boehringer Ingelheim Investigational Site

Col Obregón, Mexico

Location

1100.1470.55008 Boehringer Ingelheim Investigational Site

Col. Los Filtros, San Luis Potosí, Mexico

Location

1100.1470.55001 Boehringer Ingelheim Investigational Site

Col. Toriello Guerra, Mexico

Location

1100.1470.55007 Boehringer Ingelheim Investigational Site

Guadalajara Jal., Mexico

Location

1100.1470.55003 Boehringer Ingelheim Investigational Site

Tlalpan-México D,F, Mexico

Location

1100.1470.48003 Boehringer Ingelheim Investigational Site

Bydgoszcz, Poland

Location

1100.1470.48001 Boehringer Ingelheim Investigational Site

Chorzów, Poland

Location

1100.1470.48002 Boehringer Ingelheim Investigational Site

Szczecin, Poland

Location

1100.1470.48004 Boehringer Ingelheim Investigational Site

Warsaw, Poland

Location

1100.1470.35102 Boehringer Ingelheim Investigational Site

Cascais, Portugal

Location

1100.1470.35101 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

1100.1470.35103 Boehringer Ingelheim Investigational Site

Porto, Portugal

Location

1100.1470.40001 Boehringer Ingelheim Investigational Site

Bucharest, Romania

Location

1100.1470.40002 Boehringer Ingelheim Investigational Site

Bucharest, Romania

Location

1100.1470.34013 Boehringer Ingelheim Investigational Site

Alcalá de Henares (Madrid), Spain

Location

1100.1470.34008 Boehringer Ingelheim Investigational Site

Badalona, Spain

Location

1100.1470.34002 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1100.1470.34003 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1100.1470.34004 Boehringer Ingelheim Investigational Site

Donostia / San Sebastian, Spain

Location

1100.1470.34009 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat, Spain

Location

1100.1470.34010 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1100.1470.34012 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1100.1470.34014 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1100.1470.34015 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1100.1470.34019 Boehringer Ingelheim Investigational Site

Málaga, Spain

Location

1100.1470.34007 Boehringer Ingelheim Investigational Site

Sabadell (Barcelona), Spain

Location

1100.1470.34006 Boehringer Ingelheim Investigational Site

Santa Cruz de Tenerife, Spain

Location

1100.1470.34011 Boehringer Ingelheim Investigational Site

Vigo, Spain

Location

1100.1470.41004 Boehringer Ingelheim Investigational Site

Bern, Switzerland

Location

1100.1470.41001 Boehringer Ingelheim Investigational Site

Lugano, Switzerland

Location

1100.1470.41003 Boehringer Ingelheim Investigational Site

Sankt Gallen, Switzerland

Location

1100.1470.41002 Boehringer Ingelheim Investigational Site

Zurich, Switzerland

Location

1100.1470.44004 Boehringer Ingelheim Investigational Site

Birmingham, United Kingdom

Location

1100.1470.44001 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1100.1470.44002 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1100.1470.44005 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1100.1470.44006 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1100.1470.44003 Boehringer Ingelheim Investigational Site

Manchester, United Kingdom

Location

Related Publications (2)

• Seclen E, Soriano V, Gonzalez MM, Martin-Carbonero L, Gellermann H, Distel M, Kadus W, Poveda E. Impact of baseline HIV-1 tropism on viral response and CD4 cell count gains in HIV-infected patients receiving first-line antiretroviral therapy. J Infect Dis. 2011 Jul 1;204(1):139-44. doi: 10.1093/infdis/jir218.

  PMID: 21628668 DERIVED

• Soriano V, Arasteh K, Migrone H, Lutz T, Opravil M, Andrade-Villanueva J, Antunes F, Di Perri G, Podzamczer D, Taylor S, Domingo P, Gellermann H, de Rossi L; ARTEN investigators. Nevirapine versus atazanavir/ritonavir, each combined with tenofovir disoproxil fumarate/emtricitabine, in antiretroviral-naive HIV-1 patients: the ARTEN Trial. Antivir Ther. 2011;16(3):339-48. doi: 10.3851/IMP1745.

  PMID: 21555816 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Atazanavir Sulfate

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2006
• First Posted: October 18, 2006
• Study Start: October 1, 2006
• Primary Completion: February 1, 2011
• Last Updated: January 27, 2014
• Results First Posted: March 26, 2012

Record last verified: 2013-12

Locations

AR (4); IT (8); ES (14); DE (17); CH (4); PL (4); GB (6); RO (2); ME (6); PT (3)