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

Boehringer Ingelheim

Status and phase: Completed; Phase 4

Conditions: HIV Infections

Treatments: Drug: Atazanavir 300 mg; Drug: tenofovir DF 300 mg QD; Drug: Ritonavir 100 mg; Drug: emtricitabine 200 mg QD; Drug: Nevirapine 200 mg BID

Study type: Interventional

Funder types: Industry

Identifiers

NCT00552240

1100.1512

Details and patient eligibility

About

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).

Enrollment: 154 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

154 participants in 2 patient groups

NVP 200mg bis indie (BID)

Active Comparator group

Description:

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

Treatment:

Drug: Nevirapine 200 mg BID

Drug: emtricitabine 200 mg QD

Drug: tenofovir DF 300 mg QD

Drug: emtricitabine 200 mg QD

Drug: tenofovir DF 300 mg QD

Atazanavir 300 mg QD/ritonavir 100 mg QD

Active Comparator group

Description:

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

Treatment:

Drug: emtricitabine 200 mg QD

Drug: tenofovir DF 300 mg QD

Drug: emtricitabine 200 mg QD

Drug: tenofovir DF 300 mg QD

Drug: Ritonavir 100 mg

Drug: Atazanavir 300 mg