HIV Infections
Conditions
Brief summary
This is an open-label, randomized, parallel group pharmacokinetics trial of tipranavir/ritonavir (TPV/RTV), alone or in combination with RTV-boosted saquinavir (SQV), amprenavir (APV) or lopinavir (LPV), plus an optimized background regimen, in multiple antiretroviral (ARV) experienced HIV-1 patients. The primary objective is to determine the safety and pharmacokinetics of: TPV/RTV given with an optimized background regimen (OBR) and TPV/RTV given in combination with saquinavir, amprenavir, or Kaletra® and an optimized background regimen (OBR).
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent prior to trial participation. * Human Immunodeficiency Virus type 1 (HIV-1) infected males or females ≥18 years of age. * Acceptable laboratory screening values in Trial 1182.12 (RESIST 1) or 1182.48 (RESIST 2), excluding genotype. * Genotypic resistance report from screening visit of study RESIST 1 or RESIST 2 indicating at least three mutations at protease codons 33, 82, 84, and 90. * At least 3 consecutive months experience taking ARVs from each of the classes of Nucleoside reverse transcriptase inhibitors (NRTI), Non-nucleoside reverse transcriptase inhibitor 1 (NNRTI), and Protease Inhibitor (PI) at some point in treatment history, with at least 2 PI-based regimens, one of which must be part of the current regimen, and current PI-based Anti-retroviral (ARV) medication regimen for at least 3 months prior to randomization. * HIV-1 viral load ≥1000 copies/mL at screening. * Further inclusion criteria apply.
Exclusion criteria
* Anti-retroviral (ARV) medication naïve. * Patients on recent drug holiday, defined as off ARV medications for at least 7 consecutive days within the last 3 months. * Female patients of child-bearing potential 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 a use barrier method of contraception, or * require ethinyl estradiol administration. * Prior tipranavir use. * Use of investigational medications within 30 days before study entry or during the trial. * Further
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change of the 2nd Protease Inhibitor (PI) (APV, LPV. SQV) mean concentration (C12h) | Day 14 to Day 28 |
| Occurrence of adverse events; Proportion of patients with laboratory abnormalities; Proportion of patients with SAEs | week 4 |
Secondary
| Measure | Time frame |
|---|---|
| Assessment of patient adherence | Week 1 to 4 |
| Area under the Curve (AUC(0-12h)) of the 2nd PI (APV, LPV. SQV); Maximum concentration (Cmax) of the 2nd PI (APV, LPV. SQV); Concentration (C12h) of the 2nd PI (APV, LPV. SQV) | week 2 and 4 |
| Change in AUC(0-12h) of TPV from week 2; Change in Cmax of TPV from week 2; Change in C12h of TPV from week 2 | week 4 |
| Mean concentration (C12h) of TPV (TPV/r group); Mean concentration (C12h) of RTV (TPV/r group) | Week 1 and 2 |
| AUC(0-12h) of RTV; Cmax of RTV; C12h of RTV | week 2 and 4 |
| Change in viral load; Proportion of virologic responders | week 2, 4, 8, 16 and 24 |
| Change in AUC(0-12h) of RTV from week 2; Change in Cmax of RTV from week 2; Change in C12h of RTV from week 2 | week 4 |
| Mean concentration (C12h) of TPV (PI/TPV/r group); Mean concentration (C12h) of RTV (PI/TPV/r group) | Week 3 and 4 |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Greece, Italy, Netherlands, Portugal, Switzerland, United Kingdom, United States
Outcome results
None listed