Clinical trial NCT00275444: 3 TPV/RTV Doses in Multiple ARV Experienced Patients - Tipranavir Dose Defining Study
Official title: Double-blind, Randomized, Dose Optimization Trial of Three Doses of Tipranavir Boosted With Low Dose Ritonavir (TPV/RTV) in Multiple Antiretroviral Drug-experienced Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-01-12
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Virologic response after 2 weeks of functional monotherapy
timeFrame: At week 2
Secondary outcomes:
measure: Virologic response after 8 and 24 weeks of therapy and adverse event and laboratory safety measures.
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Arizona
city: Fountain Valley
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Long Beach
country: United States
facility: Living Hope Clinical Trials, Inc.
state: California
city: Los Angeles
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Washington
country: United States
facility: Vincent Lombardi Cancer Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Miami
country: United States
facility: 1501 N.W. 9th Ave
state: Florida
city: Orlando
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: South Miami
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: Hillsborough County Health Dept.
state: Florida
city: Vero Beach
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Georgia
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Macon
country: United States
facility: Mercer University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: CORE Center
state: Illinois
city: Chicago
country: United States
facility: Rush-Presbytarian-St Luke's Medical Center
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: HIV Outpatient Program (H.O.P)
state: Louisiana
city: Baltimore
country: United States
facility: John's Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Kansas City
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Las Vegas
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Nevada
city: Hillsborough
country: United States
facility: ID Care
state: New Jersey
city: Santa Fe
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Stony Brook
country: United States
facility: University of New York at Stony Brook
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Huntersville
country: United States
facility: Boehringer Ingelheim Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Columbia
country: United States
facility: Boehringer Ingelheim Investigational Site
state: South Carolina
city: Houston
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Texas
city: Annandale
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Virginia
city: Darlinghurst
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: New South Wales
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Ottawa
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Chest Institute - McGill University Health Centre
state: Quebec
city: Le Kremlin Bicêtre cedex
country: France
facility: Hôpital de Bicêtre
city: Montpellier cedex 5
country: France
facility: Hôpital de Chauliac
city: Nantes cedex 1
country: France
facility: Hôpital Hôtel Dieu
city: Paris cedex 10
country: France
facility: Hôpital Saint Louis
city: Paris cedex 13
country: France
facility: Hôpital de la pitié Salpetrière
city: Paris cedex 18
country: France
facility: Hôpital Bichat Claude Bernard
city: Berlin
country: Germany
facility: Epimed GmbH
city: Frankfurt/Main
country: Germany
facility: Klinikum der J.-W.-Goethe-Universität
city: Köln
country: Germany
facility: Klinik I für Innere Medizin der
city: München
country: Germany
facility: Medizinische Poliklinik
city: Milano
country: Italy
facility: Fondazione Centro S. Raffaele del Monte Tabor
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Barcelona
country: Spain
facility: Hospital Clínico y Provincial de Barcelona - HIV
city: Madrid
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: Hospital La Paz.
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal.
city: London
country: United Kingdom
facility: 4th Floor Research Office (St Stephens Centre)
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: