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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00819052
• Other study ID #: 1100.1526
• Secondary ID: 2008-004681-55
• Status: Completed
• Phase: Phase 3
• First received: January 7, 2009
• Last updated: November 7, 2014
• Start date: December 2008
• Est. completion date: January 2012

Study information

• Verified date: November 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: AFSSAPSGermany: BfArM-Bundesinstitut fuer Arzneimittel und Medizinprodukte (Federal Authorities for Drugs and Medical Products)Great Britain: MHRAUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 445
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections

Intervention

Drug:
• Nevirapine XR
Nevirapine XR
• Nevirapine XR
Nevirapine extended release
• Nevirapine IR
Nevirapine Immediate Release

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Summary of CD4 Count (Cells/Cubic Millimeter) at Baseline, Full Analysis Set Population		week 0	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 2, Observed Cases, Full Analysis Set Population		baseline, week 2	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 4, Observed Cases, Full Analysis Set Population		baseline, week 4	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 8, Observed Cases, Full Analysis Set Population		baseline, week 8	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 12, Observed Cases, Full Analysis Set Population		baseline, week 12	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 24, Observed Cases, Full Analysis Set Population		baseline, week 24	No
Secondary	Comparison of CD4 Count (Cells/Cubic Millimeter) Change From Baseline at Week 24, Observed Cases, Full Analysis Set Population		baseline, week 24	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 48, Observed Cases, Full Analysis Set Population		baseline, week 48	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 60, Observed Cases, Full Analysis Set Population		baseline, week 60	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 72, Observed Cases, Full Analysis Set Population		baseline, week 72	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 84, Observed Cases, Full Analysis Set Population		baseline, week 84	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 96, Observed Cases, Full Analysis Set Population		baseline, week 96	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 108, Observed Cases, Full Analysis Set Population		baseline, week 108	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 120, Observed Cases, Full Analysis Set Population		baseline, week 120	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 132, Observed Cases, Full Analysis Set Population		baseline, week 132	No
Secondary	Change From Baseline in CD4 Count (Cells/Cubic Millimeter) at Week 144, Observed Cases, Full Analysis Set Population		baseline, week 144	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	Changes in Safety Parameters Related to Treatment	Occurence of investigations related to treatment	until week 144	No
Secondary	Occurence of Rashes	drug-related rashes by severity	144 weeks	No
Secondary	Occurence of Hepatic Events		144 weeks	No
Secondary	New AIDS or AIDS-related Progression Event or Death		144 weeks	No
Secondary	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	No
Secondary	Genotypic Resistance Associated With Virologic Failure	Genotypic resistance associated with virologic failure.; This endpoint was not analysed due to lack of data.	48 weeks	No
Secondary	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	No

External Links

•   Link