3 TPV/RTV Doses in Multiple ARV Experienced Patients - Tipranavir Dose Defining Study

Double-blind, Randomized, Dose Optimization Trial of Three Doses of Tipranavir Boosted With Low Dose Ritonavir (TPV/RTV) in Multiple Antiretroviral Drug-experienced Subjects

A dose defining study of the protease inhibitor tipranavir (TPV), boosted with low dose ritonavir (RTV). Three dose combinations of TPV/RTV are administered to multiple antiretroviral experienced patients and the dose that achieves the best efficacy and safety as determined by evaluation of 2, 8, and 24-week virologic response and adverse event and laboratory profile measures would be selected for further clinical study.

Inclusion criteria:

• Signed informed consent prior to trial participation.
• Human immunodeficiency virus 1 (HIV-1) infected males or females > 18 years of age.
• At least 3 months experience taking Nucleoside reverse transcriptase inhibitors (NRTIs), Non-nucleoside reverse transcriptase inhibitor (NNRTIs), and Protease inhibitors (PIs).
• Current PI-based Antiretroviral (ARV) medication regimen for at least 3 months prior to randomization, and at least 3 months experience taking at least one other PI-based regimen.
• HIV-1 viral load ≥1000 copies/mL at screening.
• Genotypic resistance report indicating one or more primary PI resistance mutation(s), including 30N, 46I/L, 48V, 50V, 82A/F/T, 84V or 90M.
• Availability of 2 or more non-PI ARV medications by genotypic resistance testing, i.e. 2 drugs tested as "no evidence of resistance" or "possible resistance".
• Acceptable screening laboratory values that indicate adequate baseline organ function.
• Laboratory values are considered to be acceptable if severity is no higher than Grade 3 Gamma glutamyl transferase (GGT), Grade 2 cholesterol or triglycerides, and no higher than Grade 1 for all other tests based on the "Division of Acquired Immune Deficiency Syndrome" of National Institute of Health, USA - DAIDS - Grading Scale. All laboratory values outside these limits are subject to approval by Boehringer Ingelheim (BI).
• Further inclusion criteria apply.

Exclusion criteria:

• ARV medication naïve.

• Only one or no available ARV medications as determined by genotypic resistance testing.

• Female subjects who:

  • have a positive serum pregnancy test at screening or during the study;
  • are breast feeding;
  • are planning to become pregnant;
  • are not willing to use two methods of contraception to include at least one barrier method (e.g. latex condom plus spermicidal jelly/foam).

• Any active opportunistic infection within 60 days before study entry.

• Active Hepatitis B (HCB) or Hepatitis C (HCV) disease defined as HBsAg positive or HCV RNA positive with Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) > Grade 1.

• Prior tipranavir use.

• Use of investigational medications within 30 days before study entry or during the trial.Some expanded access drugs may be acceptable; must be approved by BI. Tenofovir, investigational at time of preparation of this protocol, is acceptable.

• Use of concomitant drugs which may significantly reduce plasma levels of the study medications.

• Further exclusion criteria apply.