HIV infection
Conditions
Interventions
Trade Name: Aptivus® (tipranavir) 250mg soft capsules
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: tipranavir
CAS Number: 174484-41-4
Current Sponsor code: TPV
Concentration unit: mg millig
Sponsors
Boehringer Ingelheim France SAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. HIV-1 infected male or female > 18 years of age. 2. Three-class (NRTI, NNRTI, and PI) treatment-experienced patients (a minimum of 3-months duration for each class) with resistance to more than one PI on the screening virtual phenotype resistance testing. 3. Patient’s optimized background regimen must contain one of the following ARV options: • A minimum of two genotypically active nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) reported as “maximal response” or “sensitive” on the screening virtual phenotype report. • A minimum of one genotypically active NRTI reported as “maximal response” or “sensitive” on the screening virtual phenotype report plus Enfuvirtide if not used previously. • A minimum of one genotypically active NRTI reported as “maximal response” or “sensitive” on the screening virtual phenotype report plus an integrase inhibitor if not used previously and if available through an expanded access program and allowed by local regulatory authorities. • A minimum of one genotypically active NRTI reported as “maximal response” or “sensitive” on the screening virtual phenotype report plus the CCR5 chemokine receptor antagonist Maraviroc (Pfizer) if available through an expanded access program, not used previously and allowed by local regulatory authorities. • Zero or one genotypically active NRTI reported as “maximal response” or “sensitive” on the screening virtual phenotype report plus two of the following drugs, Enfuvirtide, integrase inhibitor and Maraviroc if available, not used previously and allowed by local regulatory authorities. For patients who had previously taken 3TC (lamivudine) or FTC (emtricitabine), these drugs are not considered as sensitive regardless of the virtual phenotype report. 4. Patient has been on their current (failing) PI-containing regimen for at least 8 weeks prior to randomization. 5. An HIV-1 viral load of =1,000 copies/mL at screening. 6. A CD4+ cell count of = 50 cells/mm3 at screening. 7. Karnofsky performance score of = 70 (Appendix 10.7). 8. Acceptable screening laboratory values that indicate adequate baseline organ function. Laboratory values are considered acceptable if the following apply: • ALT =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous use of TPV or DRV. 2. Full genotypic resistance (reported as “minimal response”) to TPV or DRV on screening virtual phenotype: • “Minimal response” is defined by the fold change above the Virco upper clinical cutoff values. 3. Female patient of child-bearing potential who: • has a positive serum pregnancy test at screening or during the study, • is breast feeding, • is planning to become pregnant, • is not willing to use barrier methods of contraception or requires ethinyl estradiol administration. Barrier methods of contraception include diaphragm with spermicidal substance, condom for females, cervical caps and condoms. 4. History of Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any malignancy. 5. Any AIDS defining illness (Appendix 10.3.1) that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit. 6. Use of immunomodulatory drugs (such as interferon, cyclosporin, hydroxyurea and interleukin 2) within 30 days prior to randomization. 7. Current use of systemic cytotoxic chemotherapy. 8. Inability to adhere to the requirements of the protocol, including active substance abuse as assessed by the investigator. 9. All contraindications listed in the product monographs of Aptivus, Prezista and Norvir.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary endpoint of this study is time to virologic failure using VL < 50 copies/mL to determine virologic response (and VL = 500 to determine virologic rebound). ;Secondary Objective: • The key secondary endpoint for this study will be treatment response at week 48, using VL < 50 as the response criterion with the Non-Completers equals Failures (NCF) approach for handling patients that discontinue study drug early. Other secondary endpoints will include: • An Intent-To-Treat (ITT) analysis of virologic response (ITT virologic response) at week 48 with VL < 50 as the response criterion. • Response at each visit using VL < 50 copies/mL, VL < 400 copies/mL and 1 log10 copies/mL drop from baseline in VL as the response criteria using all 3 methods for handling drug discontinuations (censored (primary), NCF (key secondary), and ITT (secondary)) ;Primary end point(s): The primary endpoint of this study is time to virologic failure using VL < 50 copies/mL to determine virologic response (and VL = 500 to determine virologic rebound). | — |
Countries
Belgium, France, Germany, Greece, Italy, Portugal, Spain
Outcome results
None listed