Dose Ranging Trial of Tipranavir/Ritonavir in Treatment-Experienced HIV Infected Individuals
Summary
The purpose of this research study is to determine which of three different dose combinations of tipranavir and ritonavir, when taken with a standard approved anti-HIV drug therapy, is most effective and safe. Tipranavir is an investigational protease inhibitor which has been demonstrated to have in vitro activity against HIV-1.
Description
This study will be conducted in HIV+, multiple ARV medication experienced patients. All patients must have received treatment from each of three ARV classes: NRTIs, NNRTIs and PIs, have received at least two PI-based ARV regimens (may include the current regimen) with a viral load greater than or equal to 1000 copies/mL at the time of study entry. The two separate PI-based regimens must each have been taken for at least 3 months. At least one resistance-conferring PI-mutation (from a pre-established panel) must be present. Baseline genotypic screening will be performed and will be used in conjunction with ARV medication history to determine new background therapy for each individual subject to use.
Following genotypic screening at baseline, qualifying subjects will be randomized to one of three blinded treatment regimens. Subjects will discontinue their current protease inhibitor and initiate TPV/RTV for 2 weeks of functional monotherapy. Thereafter, the background ARV medications will be optimized and subjects will remain on blinded TPV/RTV plus optimized background therapy for the duration of the trial. Trial duration ranges between 12-32 weeks, depending on when the subject is entered into the trial and the interim analyses for determination of optimized TPV/RTV regimen is completed. On determination of the optimal TPV/RTV dose, subjects may opt to continue open-label treatment.
Study Design
Allocation: Randomized, Control: Dose Comparison, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Conditions
HIV Infections
Intervention
Protease inhibitor tipranavir
Location
Phoenix Body Positive
Phoenix
Arizona
United States
85006
Status
Completed
Source
Boehringer Ingelheim Pharmaceuticals
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00034866
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Saquinavir
An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases.
Antiretroviral Therapy, Highly Active
Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.
Antipain
An oligopeptide produced by various bacteria which acts as a protease inhibitor.
Ritonavir
An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV.
Hiv Protease
Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.
Clinical Trials
The objective of this study is to demonstrate the safety and efficacy of tipranavir/ritonavir versus an active control arm in highly treatment experienced Human immunodeficiency virus-1 in...
Demonstrate the safety and efficacy of Tipranavir/Ritonavir versus an active treatment regimen in highly treatment experienced Human Immunodeficiency virus 1(HIV-1) infected patients.
3 TPV/RTV Doses in Multiple ARV Experienced Patients - Tipranavir Dose Defining Study
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 exp...
Tipranavir is a drug with a high antiretroviral activity, also in presence of major mutations in the protease gene. However, its necessity of being co-administered with 400 mg of ritonavir...
Emergency Use Program for HTE HIV+ Patients Who Need Tipranavir Treatment
To provide early access to tipranavir and evaluate the safety and tolerance of tipranavir combined with low dose of ritonavir in patients with progressive, HIV-1 disease who have failed or...
PubMed Articles
Abstract Ritonavir-related adverse events have been reported in patients taking tipranavir/ritonavir at the licensed dosage of 500/200 mg twice daily (bid). The aim of this open-label, prospective,...
Abstract Background: In highly antiretroviral-experienced patients with a multidrug-resistant human immunodeficiency virus (HIV) infection, recommended regimens should preferentially contain 3 active...
Full-length HIV-1 Gag determines protease inhibitor.
OBJECTIVE: There is evidence that gag contributes to protease inhibitor susceptibility in treatment-experienced patients. Moreover, protease inhibitor resistance-associated mutations can arise in gag...
Discovery of novel P3-oxo inhibitor of hepatitis C virus NS3/4A serine protease.
A novel series of P3 oxo-modified macrocyclic hepatitis C virus NS3/4A serine protease inhibitor was designed, synthesized and biologically evaluated. The hydroxy-substituted inhibitor 10 demonstrated...
Serine protease inhibitor mediated peptide bond re-synthesis in diverse protein molecules.
Protease inhibitors have been extensively used in research to prevent unwanted degradation of proteins during purification and analysis. Here, we report a remarkable discovery of protease inhibitor me...
