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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Nevirapine XR
* Drug: Nevirapine XR
* Drug: Nevirapine IR


Participation Criteria
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Eligibility Criteria
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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: Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation. HIV-1 infected males or females of at least 18 years. Treatment with Viramune regimen for at least the preceding 18 weeks. Background therapy with lamivudine/ abacavir(3TC/ABC) (Kivexa® in EU; Epzicom in US), emtricitabine/tenofovir( FTC/TDF) (Truvada) or lamivudine/zidovudine 3TC/AZT (Combivir®). An HIV viral load < 50 copies/mL in preceding 3 months. An HIV viral load of < 50 copies/mL at screening (Visit 1). 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). 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. Karnofsky performance score of < 70 Exclusion criteria: Subjects who meet one or more of the following criteria will be excluded from the study: Current treatment with an HIV protease inhibitor Participation in another trial or use of an investigational medicine within two months prior to Day 1 of this study 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 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.. 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) Laboratory parameters > DAIDS grade 3 Total triglycerides (total cholesterol no restriction) Hypersensitivity to any ingredients of the test products Active drug abuse or chronic alcoholism. Hepatic cirrhosis stage Child-Pugh B or C 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 Inability to comply with protocol requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |