Dual Boosted - Protease Inhibitor (PI) Pharmacokinetics (PK) Trial (Tipranavir / Ritonavir) in Highly Treatment-experienced HIV-1 Infected Patients

Study Overview
=================
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).

Official Title
-----------------
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 Patients.

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: tipranavir
* Drug: ritonavir
* Drug: saquinavir
* Drug: amprenavir
* Drug: lopinavir


Participation Criteria
=================
Eligibility Criteria
-----------------
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 exclusion criteria apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tipranavir|nan|
|Drug: ritonavir|nan|
|Drug: saquinavir|nan|
|Drug: amprenavir|nan|
|Drug: lopinavir|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean concentration (C12h) of TPV (TPV/r group); Mean concentration (C12h) of RTV (TPV/r group) |  | Week 1 and 2 | 
| Mean concentration (C12h) of TPV (PI/TPV/r group); Mean concentration (C12h) of RTV (PI/TPV/r group) |  | Week 3 and 4 | 
| 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 | 
| 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 | 
| 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 |