Clinical trial NCT00819052: Switching Nevirapine Immediate Release( IR) Based Regimen to Nevirapine Extended Release (XR) Based Regimen in Human Immunodeficiency Virus One (HIV-1) Infected Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-01-08
Enrollment: 445
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Comparison of Virologic Response at Week 24 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 24
Secondary outcomes:
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population
timeFrame: week 2
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population
timeFrame: week 4
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population
timeFrame: week 8
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population
timeFrame: week 12
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 400 Copies/mL, Full Analysis Set Population
timeFrame: week 24
measure: 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
timeFrame: week 0 to 24
measure: Summary of CD4 Count (Cells/Cubic Millimeter) at Baseline, Full Analysis Set Population
timeFrame: week 0
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 2, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 2
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 4, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 4
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 8, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 8
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 12, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 12
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 24, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 24
measure: Comparison of CD4 Count (Cells/Cubic Millimeter) Change From Baseline at Week 24, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 24
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 48
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 60
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 72
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 84
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 96
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 108
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 120
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 132
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: week 144
measure: Number of Participants With Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
timeFrame: last available visit, up to 144 weeks
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 48, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 48
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 60, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 60
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 72, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 72
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 84, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 84
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 96, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 96
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 108, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 108
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 120, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 120
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 132, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 132
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 144, Observed Cases, Full Analysis Set Population
timeFrame: baseline, week 144
measure: Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Last Available Visit, Observed Cases, Full Analysis Set Population
timeFrame: baseline, last available visit (up to 144 weeks)
measure: Proportion of Virologic Response (Viral Load <400 Copies/mL) Trough Week 144
timeFrame: week 144
measure: Change From Baseline in VL (HIV-1 Viral Load) at Each Visit
timeFrame: week 48, 60, 72, 84, 96, 108, 120, 132, 144, last available visit
measure: Changes in Safety Parameters Related to Treatment
timeFrame: until week 144
measure: Occurence of Rashes
timeFrame: 144 weeks
measure: Occurence of Hepatic Events
timeFrame: 144 weeks
measure: New AIDS or AIDS-related Progression Event or Death
timeFrame: 144 weeks
measure: Time to Loss of Virologic Response
timeFrame: 48 weeks
measure: Genotypic Resistance Associated With Virologic Failure
timeFrame: 48 weeks
measure: Trough Plasma Concentration
timeFrame: Day 1 to week 48
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: 1100.1526.1012 Boehringer Ingelheim Investigational Site
state: California
city: Beverly Hills
country: United States
facility: 1100.1526.1014 Boehringer Ingelheim Investigational Site
state: California
city: Long Beach
country: United States
facility: 1100.1526.1011 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1100.1526.1013 Boehringer Ingelheim Investigational Site
state: California
city: Washington
country: United States
facility: 1100.1526.1001 Boehringer Ingelheim Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: 1100.1526.1004 Boehringer Ingelheim Investigational Site
state: District of Columbia
city: Clearwater
country: United States
facility: 1100.1526.1006 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami Beach
country: United States
facility: 1100.1526.1005 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1100.1526.1002 Boehringer Ingelheim Investigational Site
state: Florida
city: Berkley
country: United States
facility: 1100.1526.1003 Boehringer Ingelheim Investigational Site
state: Michigan
city: Austin
country: United States
facility: 1100.1526.1007 Boehringer Ingelheim Investigational Site
state: Texas
city: Bobigny
country: France
facility: 1100.1526.3306A Boehringer Ingelheim Investigational Site
city: Bordeaux
country: France
facility: 1100.1526.3311A Boehringer Ingelheim Investigational Site
city: La Roche sur Yon
country: France
facility: 1100.1526.3307A Boehringer Ingelheim Investigational Site
city: Le Kremlin-Bicêtre Cedex
country: France
facility: 1100.1526.3312A Boehringer Ingelheim Investigational Site
city: Lyon Cedex 3
country: France
facility: 1100.1526.3301A Boehringer Ingelheim Investigational Site
city: Marseille cedex 9
country: France
facility: 1100.1526.3310A Boehringer Ingelheim Investigational Site
city: Montpellier cedex 5
country: France
facility: 1100.1526.3308A Boehringer Ingelheim Investigational Site
city: Nantes
country: France
facility: 1100.1526.3302A Boehringer Ingelheim Investigational Site
city: Nice cedex 3
country: France
facility: 1100.1526.3304A Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1100.1526.4902 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1100.1526.4903 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 1100.1526.4904 Boehringer Ingelheim Investigational Site
city: Bonn
country: Germany
facility: 1100.1526.4905 Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: 1100.1526.4906 Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: 1100.1526.4908 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1100.1526.4909 Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: 1100.1526.4901 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1100.1526.4910 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1100.1526.4911 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1100.1526.4912 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1100.1526.4913 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 1100.1526.4907 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 1100.1526.4914 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1100.1526.4915 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1100.1526.4403 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1100.1526.4405 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 1100.1526.4404 Boehringer Ingelheim Investigational Site
city: Tooting, London
country: United Kingdom
facility: 1100.1526.4402 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: