Switching Nevirapine Immediate Release( IR) Based Regimen to Nevirapine Extended Release (XR) Based Regimen in Human Immunodeficiency Virus One (HIV-1) Infected Patients

An Open Label, Phase IIIb, Randomised Parallel Group Study to Assess the Efficacy and Safety of Switching HIV-1 Infected Patients Successfully Treated With a Nevirapine IR Based Regiment to Nevirapine XR 400 mg QD or Remaining on Nevirapine IR 200 mg BID Based Program

The primary objective of this study is to demonstrate the efficacy of nevirapine extended release (NVP XR) based regimen for HIV-1 infected patients who were receiving nevirapine immediate release (NVP IR) based regimen for at least 18 prior weeks of therapy.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nevirapine XR; Drug: Nevirapine XR; Drug: Nevirapine IR

• Study Type: Interventional
• Enrollment (Actual): 445
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bobigny, France
    • 1100.1526.3306A Boehringer Ingelheim Investigational Site
  • Bordeaux, France
    • 1100.1526.3311A Boehringer Ingelheim Investigational Site
  • La Roche sur Yon, France
    • 1100.1526.3307A Boehringer Ingelheim Investigational Site
  • Le Kremlin-Bicêtre Cedex, France
    • 1100.1526.3312A Boehringer Ingelheim Investigational Site
  • Lyon Cedex 3, France
    • 1100.1526.3301A Boehringer Ingelheim Investigational Site
  • Marseille cedex 9, France
    • 1100.1526.3310A Boehringer Ingelheim Investigational Site
  • Montpellier cedex 5, France
    • 1100.1526.3308A Boehringer Ingelheim Investigational Site
  • Nantes, France
    • 1100.1526.3302A Boehringer Ingelheim Investigational Site
  • Nice cedex 3, France
    • 1100.1526.3304A Boehringer Ingelheim Investigational Site
• Germany
  • Berlin, Germany
    • 1100.1526.4902 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1100.1526.4903 Boehringer Ingelheim Investigational Site
  • Bochum, Germany
    • 1100.1526.4904 Boehringer Ingelheim Investigational Site
  • Bonn, Germany
    • 1100.1526.4905 Boehringer Ingelheim Investigational Site
  • Düsseldorf, Germany
    • 1100.1526.4906 Boehringer Ingelheim Investigational Site
  • Frankfurt, Germany
    • 1100.1526.4909 Boehringer Ingelheim Investigational Site
  • Frankfurt/Main, Germany
    • 1100.1526.4908 Boehringer Ingelheim Investigational Site
  • Freiburg, Germany
    • 1100.1526.4901 Boehringer Ingelheim Investigational Site
  • Hamburg, Germany
    • 1100.1526.4910 Boehringer Ingelheim Investigational Site
  • Hamburg, Germany
    • 1100.1526.4911 Boehringer Ingelheim Investigational Site
  • Hamburg, Germany
    • 1100.1526.4912 Boehringer Ingelheim Investigational Site
  • Hannover, Germany
    • 1100.1526.4913 Boehringer Ingelheim Investigational Site
  • Köln, Germany
    • 1100.1526.4907 Boehringer Ingelheim Investigational Site
  • Köln, Germany
    • 1100.1526.4914 Boehringer Ingelheim Investigational Site
  • München, Germany
    • 1100.1526.4915 Boehringer Ingelheim Investigational Site
• United Kingdom
  • London, United Kingdom
    • 1100.1526.4403 Boehringer Ingelheim Investigational Site
  • London, United Kingdom
    • 1100.1526.4405 Boehringer Ingelheim Investigational Site
  • Manchester, United Kingdom
    • 1100.1526.4404 Boehringer Ingelheim Investigational Site
  • Tooting, London, United Kingdom
    • 1100.1526.4402 Boehringer Ingelheim Investigational Site
• United States
  • California
    • Beverly Hills, California, United States
      • 1100.1526.1012 Boehringer Ingelheim Investigational Site
    • Beverly Hills, California, United States
      • 1100.1526.1014 Boehringer Ingelheim Investigational Site
    • Long Beach, California, United States
      • 1100.1526.1011 Boehringer Ingelheim Investigational Site
    • Los Angeles, California, United States
      • 1100.1526.1013 Boehringer Ingelheim Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States
      • 1100.1526.1001 Boehringer Ingelheim Investigational Site
    • Washington, District of Columbia, United States
      • 1100.1526.1004 Boehringer Ingelheim Investigational Site
  • Florida
    • Clearwater, Florida, United States
      • 1100.1526.1006 Boehringer Ingelheim Investigational Site
    • Miami, Florida, United States
      • 1100.1526.1002 Boehringer Ingelheim Investigational Site
    • Miami Beach, Florida, United States
      • 1100.1526.1005 Boehringer Ingelheim Investigational Site
  • Michigan
    • Berkley, Michigan, United States
      • 1100.1526.1003 Boehringer Ingelheim Investigational Site
  • Texas
    • Austin, Texas, United States
      • 1100.1526.1007 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

HIV infected subjects treated with a Viramune based regimen.

A subject that meets the following inclusion criteria will be eligible for participation in this study:

1. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation.
2. HIV-1 infected males or females of at least 18 years.
3. Treatment with Viramune regimen for at least the preceding 18 weeks.
4. Background therapy with lamivudine/ abacavir(3TC/ABC) (Kivexa® in EU; Epzicom in US), emtricitabine/tenofovir( FTC/TDF) (Truvada) or lamivudine/zidovudine 3TC/AZT (Combivir®).
5. An HIV viral load < 50 copies/mL in preceding 3 months.
6. An HIV viral load of < 50 copies/mL at screening (Visit 1).
7. Acceptable screening laboratory values that indicate adequate baseline organ function with the following exceptions: alanine aminotrnasferase (ALT) and asparatate aminotransferase (AST) < 2.5 × upper limit of normal (ULN) Division of Acquired Immunodeficiency Syndrome (DAIDS Grade 1).
8. Willingness to abstain from ingesting medications that are listed as contraindicated in the Summary of Product Characteristics (SPC) or package insert (or PI) or Investigator's Brochure during the study.
9. Karnofsky performance score of < 70

Exclusion criteria:

Subjects who meet one or more of the following criteria will be excluded from the study:

1. Current treatment with an HIV protease inhibitor
2. Participation in another trial or use of an investigational medicine within two months prior to Day 1 of this study

3. Female patients of child-bearing potential who:

   1. Have a positive serum pregnancy test at screening.
   2. Are breast feeding.
   3. Are planning to become pregnant
   4. Are not willing to use a double-barrier methods (simultaneous use of two different methods such as diaphragm with spermicidal substance and condom) of contraception, or require ethinyl estradiol administration. Barrier methods of contraception include diaphragm with spermicidal substance, condom for females, cervical caps and condoms..
4. Laboratory parameters > DAIDS grade 2 Coagulation prothrombin time (PT), partial thromboplastin time (PTT), International Normalized ratio (INR) Hematology (absolute platelets, white blood cells (WBC), absolute neutrophil count, hemoglobin) Biochemistry (total bilirubin, amylase, serum creatinine, fasting glucose, lactate, alkaline phosphatase)
5. Laboratory parameters > DAIDS grade 3 Total triglycerides (total cholesterol no restriction)
6. Hypersensitivity to any ingredients of the test products
7. Active drug abuse or chronic alcoholism.
8. Hepatic cirrhosis stage Child-Pugh B or C
9. History of severe or acute illness within 60 days prior to Day 1, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the trial
10. Inability to comply with protocol requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NVP IR; 200 mg orally twice a day (po BID)	Drug: Nevirapine XR; Nevirapine XR; Drug: Nevirapine XR; Nevirapine extended release; Drug: Nevirapine IR; Nevirapine Immediate Release
Experimental: NVP XR; 400 mg orally once a day (po QD)	Drug: Nevirapine XR; Nevirapine XR; Drug: Nevirapine XR; Nevirapine extended release

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Virologic Response at Week 24 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Primary endpoint was the number of patients with a sustained virologic response through week 24	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 2	week 2
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 4	week 4
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 8	week 8
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 12	week 12
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 24	week 24
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		week 0 to 24
Summary of CD4 Count (Cells/Cubic Millimeter) at Baseline, Full Analysis Set Population		week 0
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 2, Observed Cases, Full Analysis Set Population		baseline, week 2
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 4, Observed Cases, Full Analysis Set Population		baseline, week 4
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 8, Observed Cases, Full Analysis Set Population		baseline, week 8
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 12, Observed Cases, Full Analysis Set Population		baseline, week 12
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 24, Observed Cases, Full Analysis Set Population		baseline, week 24
Comparison of CD4 Count (Cells/Cubic Millimeter) Change From Baseline at Week 24, Observed Cases, Full Analysis Set Population		baseline, week 24
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 48	week 48
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 60	week 60
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 72	week 72
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 84	week 84
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 96	week 96
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 108	week 108
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 120	week 120
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 132	week 132
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response through week 144	week 144
Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population	Endpoint was the number of patients with a sustained virologic response at their last available visit	last available visit, up to 144 weeks
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 48, Observed Cases, Full Analysis Set Population		baseline, week 48
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 60, Observed Cases, Full Analysis Set Population		baseline, week 60
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 72, Observed Cases, Full Analysis Set Population		baseline, week 72
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 84, Observed Cases, Full Analysis Set Population		baseline, week 84
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 96, Observed Cases, Full Analysis Set Population		baseline, week 96
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 108, Observed Cases, Full Analysis Set Population		baseline, week 108
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 120, Observed Cases, Full Analysis Set Population		baseline, week 120
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 132, Observed Cases, Full Analysis Set Population		baseline, week 132
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 144, Observed Cases, Full Analysis Set Population		baseline, week 144
Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Last Available Visit, Observed Cases, Full Analysis Set Population		baseline, last available visit (up to 144 weeks)
Proportion of Virologic Response (Viral Load <400 Copies/mL) Trough Week 144	Endpoint was the number of patients with a sustained virologic response through week 144	week 144
Change From Baseline in VL (HIV-1 Viral Load) at Each Visit		week 48, 60, 72, 84, 96, 108, 120, 132, 144, last available visit
Changes in Safety Parameters Related to Treatment	Occurence of investigations related to treatment	until week 144
Occurence of Rashes	drug-related rashes by severity	144 weeks
Occurence of Hepatic Events		144 weeks
New AIDS or AIDS-related Progression Event or Death		144 weeks
Time to Loss of Virologic Response	Kaplan-Meier Estimates of time to loss of virologic response defined as the time between the start of treatment and the time of treatment failure, up to and including the time when the last patient was on treatment for 48 weeks.	48 weeks
Genotypic Resistance Associated With Virologic Failure	Genotypic resistance associated with virologic failure. This endpoint was not analysed due to lack of data.	48 weeks
Trough Plasma Concentration	Trough plasma concentrations of Nevirapine at steady state after multiple oral administrations of Nevirapine treatments from day 1 (visit 2) to week 48 (visit 9).	Day 1 to week 48

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: January 7, 2009
• First Submitted That Met QC Criteria: January 7, 2009
• First Posted (Estimate): January 8, 2009

Study Record Updates

• Last Update Posted (Estimate): November 10, 2014
• Last Update Submitted That Met QC Criteria: November 7, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine
• Other Study ID Numbers: 1100.1526; 2008-004681-55 (EudraCT Number: EudraCT)