VERxVE Study on Efficacy and Safety of Nevirapine XR in Comparison to Nevirapine IR With Truvada in Naive HIV+ Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00561925
First received: November 20, 2007
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: nevirapine IR
Drug: nevirapine XR
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomised, Double Blind, Double Dummy, Parallel Group, Active Controlled Trial to Evaluate the Antiviral Efficacy of 400 mg QD neVirapine Extended Release Formulation in Comparison to 200 mg BID neVirapinE Immediate Release in Combination With Truvada® in Antiretroviral Therapy naïve HIV-1 Infected Patients (VERxVE)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population [ Time Frame: week 48 ] [ Designated as safety issue: No ]
    Primary endpoint was the number of patients with a sustained virologic response through week 48 using LLOQ = 50 copies/mL


Secondary Outcome Measures:
  • Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population [ Time Frame: week 0 to 144 ] [ Designated as safety issue: No ]
  • Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population [ Time Frame: week 144 ] [ Designated as safety issue: No ]
    Endpoint was the number of patients with a sustained virologic response through week 144 using LLOQ = 50 copies/mL

  • Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population [ Time Frame: week 0 to 144 ] [ Designated as safety issue: No ]
  • Comparison of HIV-1 Viral Load (log10 Copies/mL) Change From Baseline at Week 144, Full Analysis Set Population [ Time Frame: baseline, week 144 ] [ Designated as safety issue: No ]
  • Comparison of CD4+ Cell Count (Cells/Cubic Millimeter) Change From Baseline at Week 144, Full Analysis Set Population [ Time Frame: baseline, week 144 ] [ Designated as safety issue: No ]
  • Occurrence of Rashes [ Time Frame: until last patient completed 144 weeks (up to 193 weeks) ] [ Designated as safety issue: No ]
    Frequency of patients with drug related rash events by functional grouping

  • Occurrence of Elevations in Laboratory Measurement by DAIDS Grade [ Time Frame: until last patient completed 144 weeks (up to 193 weeks) ] [ Designated as safety issue: No ]
  • Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication [ Time Frame: week 0 to 144 ] [ Designated as safety issue: No ]
  • Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities [ Time Frame: week 0 to 72 ] [ Designated as safety issue: No ]
  • Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities [ Time Frame: week 0 to 72 ] [ Designated as safety issue: No ]
  • Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events [ Time Frame: week 0 to 72 ] [ Designated as safety issue: No ]
  • Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash [ Time Frame: week 0 to 72 ] [ Designated as safety issue: No ]
  • Relative Bioavailability Trough C_pre,ss,1 [ Time Frame: week 132 ] [ Designated as safety issue: No ]
    Relative bioavailability measured of trough concentrations. Analysis based on adjusted by-treatment geometric means, the adjusted geometric mean ratio of NVP XR : NVP IR and it's 90% confidence interval with p-value and the inter-individual geometric coefficient of variation.

  • Occurrence of Hepatic Events [ Time Frame: until last patient completed 144 weeks (up to 193 weeks) ] [ Designated as safety issue: No ]
    Frequency of patients with hepatitis symptoms


Enrollment: 1068
Study Start Date: November 2007
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: nevirapine XR
400 mg QD
Drug: nevirapine XR
400 mg QD
Active Comparator: nevirapine IR
200 mg BID
Drug: nevirapine IR
200 mg BID

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00561925

  Show 202 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional 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: NCT00561925     History of Changes
Other Study ID Numbers: 1100.1486, 2007-003654-29
Study First Received: November 20, 2007
Results First Received: December 13, 2011
Last Updated: March 7, 2014
Health Authority: Argentina: Administración Nacional de Medicamentos, Alimentos y Tecnologia Médica (A.N.M.A.T.)
Australia: Responsilble Ethics Committee
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada (TPD)
France: AFSSAPS
Germany: BfArM (Bundesagentur fuer Arzneimittel und Medizinalprodukte)
Great Britain: MHRA
Ireland: Irish Medicines Board
Italy: Comitato Etico Interaziendale delle ASL di Torino
Mexico: Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS)
Netherlands: Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Republic of Botswana: Ministry of Health Harvard University Research Ethics Commitee
Romania: National Medicines Agency, Bucharest
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
South Africa: MCC (Medicines Control Council)
Spain: Agencia Espanola del Medicamento y Productos Sanitarios
Switzerland: Swissmedic
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 20, 2014