Clinical trial NCT00056641: Dual Boosted - Protease Inhibitor (PI) Pharmacokinetics (PK) Trial (Tipranavir / Ritonavir) in Highly Treatment-experienced HIV-1 Infected Patients
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2003-03-21
Enrollment: 328
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Change of the 2nd Protease Inhibitor (PI) (APV, LPV. SQV) mean concentration (C12h)
timeFrame: Day 14 to Day 28
measure: Occurrence of adverse events; Proportion of patients with laboratory abnormalities; Proportion of patients with SAEs
timeFrame: week 4
Secondary outcomes:
measure: Mean concentration (C12h) of TPV (TPV/r group); Mean concentration (C12h) of RTV (TPV/r group)
timeFrame: Week 1 and 2
measure: Mean concentration (C12h) of TPV (PI/TPV/r group); Mean concentration (C12h) of RTV (PI/TPV/r group)
timeFrame: Week 3 and 4
measure: Assessment of patient adherence
timeFrame: Week 1 to 4
measure: 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)
timeFrame: week 2 and 4
measure: 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
timeFrame: week 4
measure: 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
timeFrame: week 4
measure: AUC(0-12h) of RTV; Cmax of RTV; C12h of RTV
timeFrame: week 2 and 4
measure: Change in viral load; Proportion of virologic responders
timeFrame: week 2, 4, 8, 16 and 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Arizona
city: Berkeley
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Fountain Valley
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: San Francisco
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: San Francisco
country: United States
facility: San Francisco VAMC
state: California
city: Norwalk
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Connecticut
city: Washington
country: United States
facility: Washington DC VA Medical Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: North Broward Hospital District
state: Florida
city: Fort Myers
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Sarasota
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: Boehringer Ingelheim Investigational Site
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: Macon
country: United States
facility: Mercer University School of Medicine
state: Georgia
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Boston
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
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: New York
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New York
city: Stony Brook
country: United States
facility: University of New York, 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: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
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: Tacoma
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Washington
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: Antwerpen
country: Belgium
facility: Instituut Tropische Geneeskunde
city: Bruxelles
country: Belgium
facility: Centre Hospitalier Universitaire St. Pierre
city: Gent
country: Belgium
facility: U.Z. Gent
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Canadian Immunodeficiency Research Collaborative Inc.
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Monteal
country: Canada
facility: McGill University Health Centre, Suite A5-140
state: Quebec
city: Montreal
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Montreal Chest Institute - McGill University Health Centre
state: Quebec
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Bordeaux cedex
country: France
facility: Hôpital Pellegrin
city: Caen
country: France
facility: Hôpital Côte de Nacre
city: Clamart
country: France
facility: Hôpital Antoine Beclère
city: Lyon Cedex 2
country: France
facility: Hôpital de l'Hôtel Dieu
city: Nantes
country: France
facility: Hôpital Hôtel Dieu
city: Nice cedex 3
country: France
facility: Hôpital de l'Archet
city: Paris cedex 18
country: France
facility: Hôpital Bichat Claude Bernard
city: Paris
country: France
facility: Hôpital de la Pité Salpêtrière
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Rennes cedex 9
country: France
facility: Hôpital de Pontchaillou
city: Strasbourg
country: France
facility: Hôpital civil
city: Vandoeuvre les nancy
country: France
facility: Hôpital brabois
city: Villejuif
country: France
facility: Hôpital Paul Brousse
city: Aachen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: Epimed GmbH
city: Berlin
country: Germany
facility: Universitätsklinikum Charité
city: Bonn
country: Germany
facility: Medizinische Universitätsklinik Bonn
city: Düsseldorf
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Erlangen
country: Germany
facility: Universitätsklinik Erlangen-Nürnberg
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt/Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität
city: Freiburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: Universitätsklinkum Freiburg
city: Hamburg
country: Germany
facility: ifi Institut für interdisziplinäre Infektiologie
city: Hamburg
country: Germany
facility: Universitätsklinik Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Med. Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Köln
country: Germany
facility: Klinik I für Innere Medizin der
city: Mannheim
country: Germany
facility: Facharzt für Innere Medizin,
city: München
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: Medizinische Poliklinik
city: Osnabrück
country: Germany
facility: Klinium Natruper Holz
city: Stuttgart
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1st Social Insurance Foundation (IKA) Pentelis
city: Athens
country: Greece
facility: Andreas Syggros Hosp.
city: Athens
country: Greece
facility: Evangelismos Hospital
city: Athens
country: Greece
facility: General Hospital "G. Gennimatas"
city: Athens
country: Greece
facility: Korgialenio-Benakio-Hellenic Red Cross General Hospital
city: Athens
country: Greece
facility: Sismanoglio Hospital
city: Patras
country: Greece
facility: University Hospital of Patras
city: Piraeus
country: Greece
facility: "Tzanio" Hospital
city: Thessaloniki
country: Greece
facility: AHEPA Hospital
city: Milano
country: Italy
facility: Fondazione S. Raffaele del Monte Tabor
city: Torino
country: Italy
facility: Ospedale Amedeo di Savoia
city: Amsterdam
country: Netherlands
facility: OLVG
city: Amsterdam
country: Netherlands
facility: Slotervaart Hospital
city: Den Haag
country: Netherlands
facility: Medical Centre Haaglanden
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Cascais
country: Portugal
facility: Hospital Condes Castro Guimarães
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Lisbon
country: Portugal
facility: Department of Infeccious Diseases
city: Porto
country: Portugal
facility: Hospital de São João
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: SSAT/Crusaid Institute
city: London
country: United Kingdom
facility: St Mary's Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: