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

Phase 4

Completed

• Conditions: HIV Infections
• Interventions: Drug: tenofovir DF 300 mg QD; Drug: emtricitabine 200 mg QD; Drug: Nevirapine 200 mg BID; Drug: Atazanavir 300 mg; Drug: Ritonavir 100 mg

• Registration Number: NCT00552240
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2007-09
• Study First Submitted: 2007-09-28
• Study First Submitted QC: 2007-10-31
• Study First Posted: 2007-11-01
• Primary Completion: 2010-03
• Results First Submitted: 2011-03-16
• Results First Submitted QC: 2011-04-21
• Results First Posted: 2011-05-23
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-09
• Last Update Posted: 2014-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 154

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NVP 200mg bis indie (BID)	tenofovir DF 300 mg QD	after receiving nevirapine (NVP) 200 mg quaue die (QD) for 2 weeks, pt titrated to NVP 200 mg bis in die (BID) combined with emtricitabine 200 mg QD/ tenofovir DF 300 mg QD (fixed dose combination Truvada) for 48 weeks
Atazanavir 300 mg QD/ritonavir 100 mg QD	tenofovir DF 300 mg QD	patients to receive atazanavir 300 mg QD boosted with ritonavir 100 mg QD combined with emtricitabine 200 mg QD/ tenofovir DF 300 mg QD (fixed dose combination Truvada) for 48 weeks
NVP 200mg bis indie (BID)	emtricitabine 200 mg QD	after receiving nevirapine (NVP) 200 mg quaue die (QD) for 2 weeks, pt titrated to NVP 200 mg bis in die (BID) combined with emtricitabine 200 mg QD/ tenofovir DF 300 mg QD (fixed dose combination Truvada) for 48 weeks
NVP 200mg bis indie (BID)	Nevirapine 200 mg BID	after receiving nevirapine (NVP) 200 mg quaue die (QD) for 2 weeks, pt titrated to NVP 200 mg bis in die (BID) combined with emtricitabine 200 mg QD/ tenofovir DF 300 mg QD (fixed dose combination Truvada) for 48 weeks
Atazanavir 300 mg QD/ritonavir 100 mg QD	emtricitabine 200 mg QD	patients to receive atazanavir 300 mg QD boosted with ritonavir 100 mg QD combined with emtricitabine 200 mg QD/ tenofovir DF 300 mg QD (fixed dose combination Truvada) for 48 weeks
Atazanavir 300 mg QD/ritonavir 100 mg QD	Atazanavir 300 mg	patients to receive atazanavir 300 mg QD boosted with ritonavir 100 mg QD combined with emtricitabine 200 mg QD/ tenofovir DF 300 mg QD (fixed dose combination Truvada) for 48 weeks
Atazanavir 300 mg QD/ritonavir 100 mg QD	Ritonavir 100 mg	patients to receive atazanavir 300 mg QD boosted with ritonavir 100 mg QD combined with emtricitabine 200 mg QD/ tenofovir DF 300 mg QD (fixed dose combination Truvada) for 48 weeks

Primary Outcome Measures

Name	Time	Method
Number of Participants With Virologic Response (VR)	baseline to week 48	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With HIV Viral Load < 400 Copies/ml at Week 36 of Treatment	baseline to week 36	Results within time windows, patients on-treatment
Change in CD4+ Cell Count From Baseline to Week 2.	baseline to week 2	Patients on-treatment, data within time windows
Number of Participants With Virologic Response According to the Time to Loss of Virologic Response (TLOVR) Algorithm	baseline to week 48	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.
Number of Participants With HIV Viral Load < 400 Copies/ml at Week 24 of Treatment	baseline to week 24	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 50 Copies/ml at Week 48	baseline to week 48	HIV viral load \<50 copies/ml measured at Week 48 among observed cases on-treatment.
Number of Participants With Virologic Success (FDA Definition)	baseline to week 48	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 to Virologic Response (First Confirmed Viral Load < 50 Copies/ml), All Participants	baseline to week 48	Time to response whereby patients withdrawing early were censored after their withdrawal
Number of Participants With Loss of Virologic Response Following Confirmed Virologic Response	baseline to week 24 and week 48	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)
Change in CD4+ Cell Count From Baseline to Week 6.	baseline to week 6	Patients on-treatment, data within time windows
Change in CD4+ Cell Count From Baseline to Week 8.	baseline to week 8	Patients on-treatment, data within time windows
Change in CD4+ Cell Count From Baseline to Week 36.	baseline to week 36	Patients on-treatment, data within time windows
Change in Fasting Plasma Total Cholesterol Level	baseline to week 48
Change in Fasting Plasma Triglycerides Level	baseline to week 48
Time to Virologic Response (First Confirmed Viral Load < 50 Copies/ml), Only Participants With Confirmed Viral Load < 50 Copies/ml	baseline to week 48
Number of Participants With HIV Viral Load < 50 Copies/ml at Week 2 of Treatment	baseline to week 2	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 50 Copies/ml at Week 4 of Treatment	baseline to week 4	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 50 Copies/ml at Week 6 of Treatment	baseline to week 6	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 50 Copies/ml at Week 8 of Treatment	baseline to week 8	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 50 Copies/ml at Week 12 of Treatment	baseline to week 12	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 50 Copies/ml at Week 24 of Treatment	baseline to week 24	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 50 Copies/ml at Week 36 of Treatment	baseline to week 36	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 50 Copies/ml at Week 48 of Treatment	baseline to week 48	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 400 Copies/ml at Week 2 of Treatment	baseline to week 2	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 400 Copies/ml at Week 4 of Treatment	baseline to week 4	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 400 Copies/ml at Week 6 of Treatment	baseline to week 6	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 400 Copies/ml at Week 8 of Treatment	baseline to week 8	Results within time windows, patients on-treatment
Number of Participants With HIV Viral Load < 400 Copies/ml at Week 12 of Treatment	baseline to week 12	Results within time windows, patients on-treatment
Change in CD4+ Cell Count From Baseline to Week 12.	baseline to week 12	Patients on-treatment, data within time windows
Number of Participants With HIV Viral Load < 400 Copies/ml at Week 48 of Treatment	baseline to week 48	Results within time windows, patients on-treatment
Number of Patients With Virologic Rebound to >400 Copies/ml	baseline to week 48	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)
AIDS Progression and Death: Number of Patients With a Treatment-emergent AIDS Defining Illness or an AIDS-defining Illness Leading to Death	baseline to week 48	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).
Change in CD4+ Cell Count From Baseline to Week 4.	baseline to week 4	Patients on-treatment, data within time windows
Change in CD4+ Cell Count From Baseline to Week 24.	baseline to week 24	Patients on-treatment, data within time windows
Change in CD4+ Cell Count From Baseline to Week 48.	baseline to week 48	Patients on-treatment, data within time windows
Change in Fasting High Density Lipoprotein (HDL) Cholesterol Level	baseline to week 48
Change in Fasting Low Density Lipoprotein (LDL)Cholesterol Level	baseline to week 48
Change in Fasting Total Cholesterol to High Density Lipoprotein (HDL) Ratio	baseline to week 48
Change in Framingham Score	baseline to week 48	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%.
Change in Revised Framingham Score According to the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group	baseline to week 48
Change in Glomerular Filtration Rate (GFR) From Baseline to Week 48	baseline to week 48	using 4-variable Modification of Diet in Renal Disease (MDRD) formula
Percentage Adherence by Pill Count	baseline to week 48	Number of pills not returned / number of treatment days in percent (%)
Number of Participants With Genotypic Resistance at the Time of Virologic Failure.	baseline to week 48	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.
Incidence of Patients With AIDS Progression at Each Visit	baseline to week 52	Cumulative incidence of patients with AIDS progression are shown
Proportion of Patients Reporting CNS Side Effects of Any Severity	baseline to week 52
Proportion of Patients Reporting Hepatic Events of Any Severity	baseline to week 52
Proportion of Patients Reporting Rash of Any Severity	baseline to week 52
Proportion of Patients With DAIDS Grade >= 2 Laboratory Abnormalities	baseline to week 52

Trial Locations

Locations (19)

1100.1512.24 Boehringer Ingelheim Investigational Site; 🇺🇸 Houston, Texas, United States

1100.1512.20 Boehringer Ingelheim Investigational Site; 🇺🇸 Los Angeles, California, United States

1100.1512.17 Boehringer Ingelheim Investigational Site; 🇺🇸 Fort Lauderdale, Florida, United States

1100.1512.16 Boehringer Ingelheim Investigational Site; 🇺🇸 Houston, Texas, United States

1100.1512.29 Boehringer Ingelheim Investigational Site; 🇺🇸 Maywood, Illinois, United States

1100.1512.21 Boehringer Ingelheim Investigational Site; 🇺🇸 Philadelphia, Pennsylvania, United States

1100.1512.25 Boehringer Ingelheim Investigational Site; 🇺🇸 Newark, New Jersey, United States

1100.1512.28 Boehringer Ingelheim Investigational Site; 🇺🇸 Beverly Hills, California, United States

1100.1512.18 Boehringer Ingelheim Investigational Site; 🇺🇸 Somers Point, New Jersey, United States

1100.1512.19 Boehringer Ingelheim Investigational Site; 🇺🇸 Fort Worth, Texas, United States

1100.1512.30 Boehringer Ingelheim Investigational Site; 🇺🇸 Dallas, Texas, United States

1100.1512.27 Boehringer Ingelheim Investigational Site; 🇺🇸 Annandale, Virginia, United States

1100.1512.11 Boehringer Ingelheim Investigational Site; 🇺🇸 Neptune, New Jersey, United States

1100.1512.13 Boehringer Ingelheim Investigational Site; 🇺🇸 Charleston, South Carolina, United States

1100.1512.23 Boehringer Ingelheim Investigational Site; 🇺🇸 Vero Beach, Florida, United States

1100.1512.26 Boehringer Ingelheim Investigational Site; 🇺🇸 Washington, District of Columbia, United States

1100.1512.15 Boehringer Ingelheim Investigational Site; 🇺🇸 Denver, Colorado, United States

1100.1512.14 Boehringer Ingelheim Investigational Site; 🇺🇸 Orlando, Florida, United States

1100.1512.22 Boehringer Ingelheim Investigational Site; 🇺🇸 Winston-Salem, North Carolina, United States