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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00389207
First received: October 17, 2006
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: nevirapine bid
Drug: nevirapine qd
Drug: atazanavir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Open Label Study Evaluating the Lipid Profile Difference and Efficacy of a Combined Therapy Including Tenofovir, Emtricitabine + Atazanavir / r or NVP in Naive HIV - 1 Infected Patients.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Treatment Response at Week 48 [ Time Frame: From baseline to Week 48 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Treatment Response at Week 48 (TLOVR Algorithm) [ Time Frame: From baseline to Week 48 ] [ Designated as safety issue: No ]
    Treatment response is defined as a VL <50 copies/mL measured at two consecutive visits up to Week 48 and without subsequent rebound or change of ARV therapy up to Week 48, based on time to loss of virologic response (TLOVR) algorithm, as a sensitivity analysis for the primary analysis.

  • Proportion of Patients With VL < 50 Copies/ml [ Time Frame: From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT ] [ Designated as safety issue: No ]
    VL <50 copies/mL among observed patients on treatment at each visit, with the final visit at Week 144 or end of trial (EOT) for the patient

  • Proportion of Patients With VL < 400 Copies/ml [ Time Frame: From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT ] [ Designated as safety issue: No ]
    VL <400 copies/mL among observed patients on treatment at each visit, with the final visit at Week 144 or end of trial (EOT)

  • Change in CD4+ Count From Baseline [ Time Frame: From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT ] [ Designated as safety issue: No ]
    Change in CD4+ cell count from baseline among patients on treatment at each visit, with the final visit at Week 144 or EOT

  • Change in Framingham Score From Baseline [ Time Frame: From baseline to Weeks 48, 96 and 144/EOT ] [ Designated as safety issue: No ]
    Change in the estimated risk of cardiovascular disease using the Framingham algorithm from baseline to after 48, 96 and 144 weeks, last observation carried forward (LOCF). The score is based on age, gender, systolic blood pressure, total cholesterol, high density lipoprotein cholesterol and smoking status. Scores range from 0 to 21 with higher scores indicating a greater risk.

  • Change in Mental Health Summary (MHS) Score From Baseline [ Time Frame: From baseline to Weeks 48, 96 and 144/EOT ] [ Designated as safety issue: No ]
    Quality of life (QoL) assessment by change in MHS score from baseline to after 48, 96 and 144 weeks (observed cases), from the Medical Outcomes Study HIV Health Survey (MOS-HIV), a 35-item self-administered questionnaire including 10 scales covering: health perceptions, pain, physical functioning, role functioning, social and cognitive functioning, mental health, energy/fatigue, health distress, and QoL. The MHS is a weighted average of the 10 scales and ranges from 0 to 100 with higher scores indicating better QoL.

  • Change in Physical Health Summary (PHS) Score From Baseline [ Time Frame: From baseline to Weeks 48, 96 and 144/EOT ] [ Designated as safety issue: No ]
    QoL assessment by change in PHS score from baseline to after 48, 96 and 144 weeks (observed cases), from the MOS-HIV, a 35-item self-administered questionnaire including 10 scales covering: health perceptions, pain, physical functioning, role functioning, social and cognitive functioning, mental health, energy/fatigue, health distress, and QoL. The PHS is a weighted average of the 10 scales and ranges from 0 to 100 with higher scores indicating better QoL.

  • Number of Patients Hospitalized [ Time Frame: From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT ] [ Designated as safety issue: No ]
    Cost effectiveness assessment by number of patients hospitalized

  • Non-scheduled Physician Visits [ Time Frame: From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT ] [ Designated as safety issue: No ]
    Cost effectiveness assessment by number of patients with non-scheduled physician visits

  • Genotypic Resistance Associated With Virologic Failure [ Time Frame: From baseline to Week 48 ] [ Designated as safety issue: No ]
    Number of treatment-emergent drug-associated substitutions in patients with virological failure up to Week 48. The total number of genotypic mutations in those patients who were virologic failures is given, not the number of patients with mutations.

  • Treatment-emergent AIDS-defining Illness [ Time Frame: From baseline to Week 144 ] [ Designated as safety issue: No ]
    Treatment-emergent AIDS-defining illness (tr.-emerg. AIDS-def.illness) including worsening during treatment

  • Treatment-emergent AIDS-defining Illness Leading to Death [ Time Frame: From baseline to Week 144 ] [ Designated as safety issue: No ]
    Patients with an AIDS-defining illness leading to death broken out by treatment. Statistical analysis shows time to death from AIDS-defining illness.

  • Lipodystrophy [ Time Frame: From baseline to Week 144 ] [ Designated as safety issue: No ]
    Number of patients with AE lipodystrophy

  • Serum Lipid Abnormalities [ Time Frame: From baseline to Week 144 ] [ Designated as safety issue: No ]
    Number of patients with AE elevated serum lipids (i.e. hypercholesterolaemia)

  • Glycaemic Abnormalities [ Time Frame: From baseline to Week 144 ] [ Designated as safety issue: No ]
    Number of patients with AE elevated serum glucose

  • Treatment Response at Week 96 [ Time Frame: From baseline to Week 96 ] [ Designated as safety issue: No ]
    Treatment response is defined as a viral load (VL) <50 copies/mL measured at two consecutive visits prior to Week 96 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 96.

  • Treatment Response at Week 144 [ Time Frame: From baseline to Week 144 ] [ Designated as safety issue: No ]
    Treatment response is defined as a viral load (VL) <50 copies/mL measured at two consecutive visits prior to Week 144 and without subsequent rebound or change of antiretroviral (ARV) therapy prior to Week 144.

  • Proportion of Patients With Virological Rebound With VL >=50 Copies/mL After CVR (Confirmed Virological Response) at Week 24, 48, 96, 144 [ Time Frame: at Week 24, 48, 96, 144 ] [ Designated as safety issue: No ]
    The analyses of virologic rebound were performed on the original values at each visit(ORGV) rather than calculated results within time windows (CAL)

  • Proportion of Patients With Virological Rebound With VL >=400 Copies/mL After CVR at Week 24, 48, 96, 144 [ Time Frame: at Week 24, 48, 96, 144 ] [ Designated as safety issue: No ]
    The analyses of virologic rebound were performed on the original values at each visit(ORGV) rather than calculated results within time windows (CAL)

  • Proportion of Patients With Virologic Failure at Week 48, 96, 144 [ Time Frame: at Week 48, 96, 144 ] [ Designated as safety issue: No ]
  • Time to Treatment Response (First Confirmed VL<50 Copies/mL) [ Time Frame: baseline to week 144 ] [ Designated as safety issue: No ]
    Time to treatment response was defined as the time from start of treatment until the first measurement of the first confirmed virological response

  • Time to Loss of Virologic Response (Rebound) [ Time Frame: Baseline to week 144 ] [ Designated as safety issue: No ]
    Time to loss of virologic response (TLOVR) was defined as the time from start of treatment to the first measurement showing VL ≥ 50 copies/mL in the first virologic rebound, after having a confirmed virological response.

  • Time to Treatment Failure [ Time Frame: baseline to week 144 ] [ Designated as safety issue: No ]
    Treatment failure is defined as the occurrence of the first of at least one of the following events: early discontinuation of trial drug, change in ARV therapy, failure to achieve an HIV RNA count < 50 copies/mL up to Visit 10 (week 48) or loss of virologic response

  • Change in the Calculated Glomerular Filtration Rate (GFR) at Week 48, 96 and 144 [ Time Frame: From baseline to Week 48, 96, 144 ] [ Designated as safety issue: No ]
    Calculations based on the MDRD algorithm.

  • Proportion of Patients With >= DAIDS Grade 2 Laboratory Abnormalities [ Time Frame: week 148 ] [ Designated as safety issue: No ]
  • Proportion of Patients Reporting Rash of Any Severity [ Time Frame: week 148 ] [ Designated as safety issue: No ]
    Proportion of Patients reporting rash of any severity

  • Proportion of Patients Reporting Hepatic Events of Any Severity [ Time Frame: week 148 ] [ Designated as safety issue: No ]
    Proportion of Patients reporting hepatic events of any severity

  • Proportion of Patients Reporting CNS (Central Nervous System) Side Effects of Any Severity [ Time Frame: week 148 ] [ Designated as safety issue: No ]
    Proportion of Patients reporting CNS (central nervous system) side effects of any severity

  • Change of Cholesterol Values From Baseline to Week 48, 96, 144 [ Time Frame: baseline to week 48, 96, 144 ] [ Designated as safety issue: No ]
    Changes frombaseline in total cholesterol, LDL-cholesterol(LDL-c) and HDL

  • Changes of Apolipoprotein Values From Baseline to Week 48, 96, 144 [ Time Frame: baseline to week 48, 96, 144 ] [ Designated as safety issue: No ]
    Changes frombaseline apolipoprotein A1 & B

  • Change of hsCRP From Baseline to Week 48, 96, 144 [ Time Frame: baseline to week 48, 96, 144 ] [ Designated as safety issue: No ]
    Change of hsCRP from baseline to week 48, 96, 144

  • Change of Total Triglycerides From Baseline to Week 48, 96, 144 [ Time Frame: baseline to week 48, 96, 144 ] [ Designated as safety issue: No ]
    Change of total triglycerides from baseline to week 48, 96, 144

  • Change of Total Cholesterol to HDL-cholesterol Ratio From Baseline to Week 48, 96, 144 [ Time Frame: baseline to week 48, 96, 144 ] [ Designated as safety issue: No ]
    Change of Total cholesterol to HDL-cholesterol ratio from baseline to week 48, 96, 144


Enrollment: 576
Study Start Date: October 2006
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: NVP bid
nevirapine (NVP) 200 mg BID in combination with emtricitabine (FTC) and tenofovir DF (TDF)
Drug: nevirapine bid
nevirapine twice daily
Experimental: NVP qd
nevirapine (NVP) 400 mg QD in combination with emtricitabine (FTC) and tenofovir DF (TDF)
Drug: nevirapine qd
nevirapine once daily
Active Comparator: ATZ/r
ritonavir-boosted atazanavir in combination with emtricitabine (FTC) and tenofovir DF (TDF)
Drug: atazanavir
atazanavir once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Inclusion Criteria:

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

Exclusion criteria:

Exclusion Criteria:

  1. Active drug abuse or chronic alcoholism at the investigator's discretion
  2. Hepatic cirrhosis stage Child-Pugh B or C
  3. 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
  4. Laboratory parameters Division of Acquired Immunodeficiency Syndrome (DAIDS) > grade 2 (triglycerides > DAIDS grade 3; total cholesterol no restrictions)
  5. 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)
  6. Hypersensitivity to any ingredients of the test products
  7. 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
  8. Patients who are receiving other concomitant treatments which are not permitted
  9. Use of other investigational medications within 30 days before study entry or during the trial
  10. 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)
  11. Patients with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma
  12. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit
  13. Patients who are receiving systemic treatment for malignant disease
  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: NCT00389207

  Show 68 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00389207     History of Changes
Other Study ID Numbers: 1100.1470, 2005-004330-40
Study First Received: October 17, 2006
Results First Received: January 13, 2012
Last Updated: December 9, 2013
Health Authority: Argentina: A.N.M.A.T. (Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica)
Germany: Federal Institute for Drugs and Medical Devices
Great Britain: MHRA
Italy: Comitato Etico dell'Azienda Osp. Riuniti di Bergamo - Bergamo
Mexico: Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency, Bucharest
Spain: Agencia Espanola del Medicamento y Productos Sanitarios
Switzerland: Swissmedic Schweizerisches Heilmittelinstitut (Swiss Agency for Therapeutic Products)

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

ClinicalTrials.gov processed this record on September 14, 2014