VERxVE Study on Efficacy and Safety of Nevirapine XR in Comparison to Nevirapine IR With Truvada in Naive HIV+ Patients
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: nevirapine IR; nevirapine XR
Intervention description: 200 mg BID; 400 mg QD
Intervention MeSH terms: Nevirapine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 1068.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the efficacy of 400 mg QD nevirapine
      extended release (NVP XR) formulation versus 200 mg BID nevirapine immediate release (NVP IR)
      in ARV therapy naïve HIV-1 infected patients after 48 weeks of treatment. Secondary
      objectives are to evaluate safety and pharmacokinetics of NVP XR and NVP IR.
    

Eligibility criteria:

        Inclusion criteria:

          1. Signed informed consent in accordance with Good Clinical Practice and local regulatory
             requirements prior to trial participation

          2. HIV-1 infected males or females >= 18 years of age with positive serology (ELISA)
             confirmed by Western blot

          3. No previous antiretroviral treatment

          4. Males with CD4+ counts >50 - <400 cells/ml or females with CD4+ counts >50-<250
             cells/ml

          5. Adequate renal function defined as a calculated creatinine clearance (CLCr) greater
             than or equal to 50 mL/min according to the Cockcroft-Gault formula as follows:

             Male: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in
             mg/dl) = CLCr (mL/min).

             Female: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in
             mg/dl) x 0.85 = CLCr (mL/min).

          6. Karnofsky score >70 (see Appendix 10.4)

          7. An HIV-1 viral load of 1,000 copies/mL

          8. Willingness to initiate CD4+ cell count-guided chemoprophylaxis to prevent important
             opportunistic infections as defined in Appendix 10.2

          9. Willingness to abstain from ingesting substances which may alter plasma study drug
             levels by interaction with the cytochrome P450 system (listed in Appendix 10.3) during
             the study.

         10. For centers participating in the PK substudy only: Written informed consent in
             accordance with GCP and local legislation for participation in the PK substudy.
             Refusal to participate in the PK substudy is not an exclusion criterion for
             participation in the trial. Only study centers with previous experience and equipped
             in handling PK samples are eligible for participation in the substudy.

        Exclusion criteria:

          1. Active drug abuse or chronic alcoholism at the investigator's discretion

          2. Active hepatitis B or C disease, defined as HBsAg-positive and HBV-DNA-positive or
             HCV-RNA-positive

          3. Female patients of child-bearing potential who: are pregnant 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 Note: During participation in this study,
             females and males have to use barrier methods of contraception in addition or instead
             of ethinyl estradiol containing oral contraceptives.

          4. Laboratory parameters >DAIDS Grade 2

          5. ALT/AST > DAIDS Grade 1

          6. Hypersensitivity to any ingredients of the test products

          7. Previous use of Viramune® (nevirapine) or any other antiretroviral agents (does not
             include use of single dose NVP for the prevention of mother to child transmission)

          8. Resistance to NNRTIs or either one of the components of Truvada® (emtricitabine or
             tenofovir disoproxil fumarate) or lamivudine (3TC) based on HIV-1 genotypic resistance
             testing report obtained at screening

          9. Patients who are receiving other concomitant treatments which are not permitted, as
             described in the prescribing information

         10. Use of investigational medications (any experimental agent other than the study
             regimen) within 30 days before study entry or during the trial

         11. Use of immunomodulatory drugs within 30 days before study entry or during the trial
             (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2)

         12. Patients who have been diagnosed with malignant disease

         13. Patients who in the opinion of the investigator are not candidates for inclusion in
             the study

         14. Patient with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's
             Sarcoma (KS), and/or any lymphoma

         15. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment
             for at least 12 weeks at screening visit