Nevirapine vs. Atazanavir Boosted With Ritonavir on a Background of Truvada in Human Immunodeficiency Virus (HIV) Infected Naive Patients (NEwArT)

Boehringer Ingelheim154 enrolled

Overview

The aim of this clinical trial is to compare the efficacy and safety of ritonavir (RTV)-boosted atazanavir with nevirapine, each on a background of emtricitabine and tenofovir disoproxil fumarate (DF).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

154

Conditions

HIV Infections

Interventions

tenofovir DF 300 mg QDDRUG

300 mg QD

tenofovir DF 300 mg QDDRUG

300 mg QD

emtricitabine 200 mg QDDRUG

200 mg QD

emtricitabine 200 mg QD

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 greater than or equal to 18 years of age with documented positive serology Enzyme-linked Immuno Sorbert Assay (ELISA) confirmed by Western blot 3. No prior nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) use of more than 10 days AND 4. No prior use of other classes of antiretrovirals (ARVs) of more than 2 weeks duration 5. Males with CD4+ count less than 400 cells/mm cubed or females with CD4+ count less than 250 cells/mm cubed 6. NVP and ATV/r susceptibility on screening HIV-1 genotypic resistance assay 7. Adequate renal function defined as a calculated creatinine clearance greater than or equal to50 ml/min according to the Cockcroft-Gault formula 8. Karnofsky score greater than or equal to 70 (see Appendix 10.7) 9. Acceptable medical history, as assessed by the investigator Exclusion criteria: 1. History of active drug or alcohol abuse within 2 years prior to study entry (at the investigators discretion) 2. Hepatic cirrhosis with stage Child-Pugh B or C hepatic impairment 3. Female patients of child-bearing potential who: have a positive serum pregnancy test at screening, 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 greater than Division of Aids (National Institute of Health, USA) (DAIDS) grade 2 (triglycerides greater than DAIDS grade 3, total cholesterol no restrictions, see Appendix 10.1) 5. Active hepatitis B or C disease, defined as HBsAg-positive or Hepatitis C Virus (HCV) RNA positive with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ALT/AST greater than2.5x Upper Limit of Normal (ULN) (greater than DAIDS grade 1) 6. Known hypersensitivity to any ingredients in nevirapine or atazanavir 7. Patients who are receiving concomitant treatments which are not permitted, as listed in Appendix 10.6 8. Use of other investigational medications within 30 days before study entry or during the trial 9. 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) 10. Patients with Progressive Multifocal Leukoencephalopathy (PML), visceral Kaposi's Sarcoma (KS), and/or any lymphoma 11. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at the screening visit 12. Patients who are receiving systemic chemotherapy

Locations (19)

1100.1512.28 Boehringer Ingelheim Investigational Site

Beverly Hills, California, United States

Outcomes

Primary Outcomes

Number of Participants With Virologic Response (VR)

VR is defined as HIV viral load of \<50 copies/ml measured at two consecutive visits PRIOR TO Week 48 and without subsequent rebound or change of ARV therapy prior to Week 48.

Time frame: baseline to week 48

Secondary Outcomes

Number of Participants With Virologic Response According to the Time to Loss of Virologic Response (TLOVR) Algorithm

HIV viral load \<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.

Time frame: baseline to week 48

Number of Participants With HIV Viral Load < 50 Copies/ml at Week 48

HIV viral load \<50 copies/ml measured at Week 48 among observed cases on-treatment.

Time frame: baseline to week 48

Number of Participants With Virologic Success (FDA Definition)

HIV viral load \<50 copies/ml measured in the Week 48 window whereby patients withdrawing early and patients without a Week 48 assessment are considered failures. Includes all participants in full analysis set (FAS).

Time frame: baseline to week 48

Time to Virologic Response (First Confirmed Viral Load < 50 Copies/ml), All Participants

Time to response whereby patients withdrawing early were censored after their withdrawal

Time frame: baseline to week 48

Time to Virologic Response (First Confirmed Viral Load < 50 Copies/ml), Only Participants With Confirmed Viral Load < 50 Copies/ml

Time frame: baseline to week 48

Number of Participants With Loss of Virologic Response Following Confirmed Virologic Response

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Nevirapine 200 mg BIDDRUG

200 mg BID

Atazanavir 300 mgDRUG

300 mg QD

Ritonavir 100 mgDRUG

100 mg QD

1100.1512.20 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

1100.1512.15 Boehringer Ingelheim Investigational Site

Denver, Colorado, United States

1100.1512.26 Boehringer Ingelheim Investigational Site

Washington D.C., District of Columbia, United States

1100.1512.17 Boehringer Ingelheim Investigational Site

Fort Lauderdale, Florida, United States

1100.1512.14 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

1100.1512.23 Boehringer Ingelheim Investigational Site

Vero Beach, Florida, United States

1100.1512.29 Boehringer Ingelheim Investigational Site

Maywood, Illinois, United States

1100.1512.11 Boehringer Ingelheim Investigational Site

Neptune City, New Jersey, United States

1100.1512.25 Boehringer Ingelheim Investigational Site

Newark, New Jersey, United States

...and 9 more locations

HIV viral load \> 50 copies/ml on two consecutive measurements separated by at least 2 weeks, after confirmed virologic response (2 consecutive HIV viral load values \< 50 copies/ml)

Time frame: baseline to week 24 and week 48

Number of Participants With HIV Viral Load < 50 Copies/ml at Week 2 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 2

Number of Participants With HIV Viral Load < 50 Copies/ml at Week 4 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 4

Number of Participants With HIV Viral Load < 50 Copies/ml at Week 6 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 6

Number of Participants With HIV Viral Load < 50 Copies/ml at Week 8 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 8

Number of Participants With HIV Viral Load < 50 Copies/ml at Week 12 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 12

Number of Participants With HIV Viral Load < 50 Copies/ml at Week 24 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 24

Number of Participants With HIV Viral Load < 50 Copies/ml at Week 36 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 36

Number of Participants With HIV Viral Load < 50 Copies/ml at Week 48 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 48

Number of Participants With HIV Viral Load < 400 Copies/ml at Week 2 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 2

Number of Participants With HIV Viral Load < 400 Copies/ml at Week 4 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 4

Number of Participants With HIV Viral Load < 400 Copies/ml at Week 6 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 6

Number of Participants With HIV Viral Load < 400 Copies/ml at Week 8 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 8

Number of Participants With HIV Viral Load < 400 Copies/ml at Week 12 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 12

Number of Participants With HIV Viral Load < 400 Copies/ml at Week 24 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 24

Number of Participants With HIV Viral Load < 400 Copies/ml at Week 36 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 36

Number of Participants With HIV Viral Load < 400 Copies/ml at Week 48 of Treatment

Results within time windows, patients on-treatment

Time frame: baseline to week 48

Number of Patients With Virologic Rebound to >400 Copies/ml

HIV viral load \>400 copies/ml on two consecutive measurements separated by at least 2 weeks, after confirmed virologic response (2 consecutive HIV viral load values \< 50 copies/ml)

Time frame: baseline to week 48

AIDS Progression and Death: Number of Patients With a Treatment-emergent AIDS Defining Illness or an AIDS-defining Illness Leading to Death

AIDS defining illnesses include: Aspergillosis, Bartonellosis, Candidiasis, Cervical cancer, Chagas disease, Coccidiodomycosis, Cryptococcosis, Cytomegalovirus retinus, encephalopathy, Herpes Simplex Virus, Histoplasmosis, Isosporiasis, Kaposi's sarcoma, Leishmaniasis, Microsporidiosis, Mycobacterium avium complex, mycobacterium (non-tuberculous), Nocardiosis, Pneumocystis carinii pneumonia, Pneumonia, Progressive Multifocal Leukoencephalopathy, Rhodococcus equi, Salmonella, Toxoplasmosis, Wasting. Number of cases (no time-to analysis was performed due to small numbers).

Time frame: baseline to week 48

Change in CD4+ Cell Count From Baseline to Week 2.

Patients on-treatment, data within time windows

Time frame: baseline to week 2

Change in CD4+ Cell Count From Baseline to Week 4.

Patients on-treatment, data within time windows

Time frame: baseline to week 4

Change in CD4+ Cell Count From Baseline to Week 6.

Patients on-treatment, data within time windows

Time frame: baseline to week 6

Change in CD4+ Cell Count From Baseline to Week 8.

Patients on-treatment, data within time windows

Time frame: baseline to week 8

Change in CD4+ Cell Count From Baseline to Week 12.

Patients on-treatment, data within time windows

Time frame: baseline to week 12

Change in CD4+ Cell Count From Baseline to Week 24.

Patients on-treatment, data within time windows

Time frame: baseline to week 24

Change in CD4+ Cell Count From Baseline to Week 36.

Patients on-treatment, data within time windows

Time frame: baseline to week 36

Change in CD4+ Cell Count From Baseline to Week 48.

Patients on-treatment, data within time windows

Time frame: baseline to week 48

Change in Fasting Plasma Total Cholesterol Level

Time frame: baseline to week 48

Change in Fasting Plasma Triglycerides Level

Time frame: baseline to week 48

Change in Fasting High Density Lipoprotein (HDL) Cholesterol Level

Time frame: baseline to week 48

Change in Fasting Low Density Lipoprotein (LDL)Cholesterol Level

Time frame: baseline to week 48

Change in Fasting Total Cholesterol to High Density Lipoprotein (HDL) Ratio

Time frame: baseline to week 48

Change in Framingham Score

Framingham prediction of 10-year risk of Coronary Heart Disease (CHD) outcomes (myocardial infarction \[MI\] or CHD death) based on the patient's gender, age, systolic blood pressure, total cholesterol, HDL-c and smoking status. The scale for the estimated risk ranges from 0 to 30%.

Time frame: baseline to week 48

Change in Revised Framingham Score According to the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group

Time frame: baseline to week 48

Change in Glomerular Filtration Rate (GFR) From Baseline to Week 48

using 4-variable Modification of Diet in Renal Disease (MDRD) formula

Time frame: baseline to week 48

Percentage Adherence by Pill Count

Number of pills not returned / number of treatment days in percent (%)

Time frame: baseline to week 48

Number of Participants With Genotypic Resistance at the Time of Virologic Failure.

Genotypic resistance was measured by the following: Plasma samples for HIV-1 resistance were analyzed using a standard clinical assay that generates a virtual phenotypic interpretation of HIV-1 sequence data and predicts susceptibility or resistance of the isolate to approved ARVs. This analysis has not been performed.

Time frame: baseline to week 48

Incidence of Patients With AIDS Progression at Each Visit

Cumulative incidence of patients with AIDS progression are shown

Time frame: baseline to week 52

Proportion of Patients Reporting CNS Side Effects of Any Severity

Time frame: baseline to week 52

Proportion of Patients Reporting Hepatic Events of Any Severity

Time frame: baseline to week 52

Proportion of Patients Reporting Rash of Any Severity

Time frame: baseline to week 52

Proportion of Patients With DAIDS Grade >= 2 Laboratory Abnormalities

Time frame: baseline to week 52