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

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.

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).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: tipranavir; Drug: ritonavir; Drug: saquinavir; Drug: amprenavir; Drug: lopinavir

• Study Type: Interventional
• Enrollment: 328
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia
      • Boehringer Ingelheim Investigational Site
    • Darlinghurst, New South Wales, Australia
      • St. Vincent's Hospital
• Belgium
  • Antwerpen, Belgium
    • Instituut Tropische Geneeskunde
  • Bruxelles, Belgium
    • Centre Hospitalier Universitaire St. Pierre
  • Gent, Belgium
    • U.Z. Gent
• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster University Medical Centre
    • Toronto, Ontario, Canada
      • Toronto General Hospital
    • Toronto, Ontario, Canada
      • Canadian Immunodeficiency Research Collaborative Inc.
    • Toronto, Ontario, Canada
      • Boehringer Ingelheim Investigational Site
  • Quebec
    • Monteal, Quebec, Canada
      • McGill University Health Centre, Suite A5-140
    • Montreal, Quebec, Canada
      • Montreal Chest Institute - McGill University Health Centre
    • Montreal, Quebec, Canada
      • Boehringer Ingelheim Investigational Site
• Denmark
  • Hvidovre, Denmark
    • Hvidovre Hospital
  • København Ø, Denmark
    • Rigshospitalet
  • Odense C, Denmark
    • Odense Universitetshospital
• France
  • Bordeaux cedex, France
    • Hôpital Pellegrin
  • Caen, France
    • Hopital Cote de Nacre
  • Clamart, France
    • Hôpital Antoine Béclère
  • Lyon Cedex 2, France
    • Hopital de l'Hotel Dieu
  • Nantes, France
    • Hôpital Hotel Dieu
  • Nice cedex 3, France
    • Hopital de l'Archet
  • Paris, France
    • Hôpital Saint Antoine
  • Paris, France
    • Hopital Europeen Georges Pompidou
  • Paris, France
    • Hôpital de la Pité Salpêtrière
  • Paris cedex 18, France
    • Hopital Bichat Claude Bernard
  • Rennes cedex 9, France
    • Hôpital de Pontchaillou
  • Strasbourg, France
    • Hôpital Civil
  • Vandoeuvre les nancy, France
    • Hôpital Brabois
  • Villejuif, France
    • Hopital Paul Brousse
• Germany
  • Aachen, Germany
    • Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • EPIMED GmbH
  • Berlin, Germany
    • Universitätsklinikum Charité
  • Bonn, Germany
    • Medizinische Universitätsklinik Bonn
  • Düsseldorf, Germany
    • Boehringer Ingelheim Investigational Site
  • Düsseldorf, Germany
    • Universitätsklinikum Düsseldorf
  • Erlangen, Germany
    • Universitätsklinik Erlangen-Nürnberg
  • Essen, Germany
    • Universitätsklinikum Essen
  • Frankfurt/Main, Germany
    • Klinikum der Johann Wolfgang Goethe-Universität
  • Freiburg, Germany
    • Boehringer Ingelheim Investigational Site
  • Freiburg, Germany
    • Universitätsklinkum Freiburg
  • Hamburg, Germany
    • ifi Institut für interdisziplinäre Infektiologie
  • Hamburg, Germany
    • Universitätsklinik Hamburg-Eppendorf
  • Hannover, Germany
    • Med. Hochschule Hannover
  • Heidelberg, Germany
    • Universitätsklinikum Heidelberg
  • Köln, Germany
    • Klinik I für Innere Medizin der
  • Mannheim, Germany
    • Facharzt für Innere Medizin,
  • München, Germany
    • Boehringer Ingelheim Investigational Site
  • München, Germany
    • Medizinische Poliklinik
  • Osnabrück, Germany
    • Klinium Natruper Holz
  • Stuttgart, Germany
    • Boehringer Ingelheim Investigational Site
• Greece
  • Athens, Greece
    • Evangelismos Hospital
  • Athens, Greece
    • 1st Social Insurance Foundation (IKA) Pentelis
  • Athens, Greece
    • Andreas Syggros Hosp.
  • Athens, Greece
    • General Hospital "G. Gennimatas"
  • Athens, Greece
    • Korgialenio-Benakio-Hellenic Red Cross General Hospital
  • Athens, Greece
    • Sismanoglio Hospital
  • Patras, Greece
    • University Hospital of Patras
  • Piraeus, Greece
    • "Tzanio" Hospital
  • Thessaloniki, Greece
    • AHEPA Hospital
• Italy
  • Milano, Italy
    • Fondazione S. Raffaele del Monte Tabor
  • Torino, Italy
    • Ospedale Amedeo di Savoia
• Netherlands
  • Amsterdam, Netherlands
    • Slotervaart Hospital
  • Amsterdam, Netherlands
    • OLVG
  • Den Haag, Netherlands
    • Medical Centre Haaglanden
  • Rotterdam, Netherlands
    • Erasmus Medical Centre
• Portugal
  • Cascais, Portugal
    • Hospital Condes Castro Guimarães
  • Coimbra, Portugal
    • Hospitais da universidade de Coimbra
  • Lisbon, Portugal
    • Department of Infeccious Diseases
  • Porto, Portugal
    • Hospital de Sao Joao
• Switzerland
  • Basel, Switzerland
    • Universitätsspital Basel
  • St. Gallen, Switzerland
    • Kantonsspital St. Gallen
  • Zürich, Switzerland
    • Universitätsspital Zürich
• United Kingdom
  • London, United Kingdom
    • Royal Free Hospital
  • London, United Kingdom
    • St Mary's Hospital
  • London, United Kingdom
    • SSAT/Crusaid Institute
• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Boehringer Ingelheim Investigational Site
  • California
    • Berkeley, California, United States
      • Boehringer Ingelheim Investigational Site
    • Fountain Valley, California, United States
      • Boehringer Ingelheim Investigational Site
    • Los Angeles, California, United States
      • Boehringer Ingelheim Investigational Site
    • San Francisco, California, United States
      • Boehringer Ingelheim Investigational Site
    • San Francisco, California, United States
      • Kaiser Permanente Medical Center
    • San Francisco, California, United States
      • San Francisco VAMC
  • Connecticut
    • Norwalk, Connecticut, United States
      • Boehringer Ingelheim Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States
      • Washington DC VA Medical Center
  • Florida
    • Fort Lauderdale, Florida, United States
      • North Broward Hospital District
    • Fort Myers, Florida, United States
      • Boehringer Ingelheim Investigational Site
    • Miami, Florida, United States
      • Boehringer Ingelheim Investigational Site
    • Orlando, Florida, United States
      • Boehringer Ingelheim Investigational Site
    • Sarasota, Florida, United States
      • Boehringer Ingelheim Investigational Site
    • Tampa, Florida, United States
      • Boehringer Ingelheim Investigational Site
    • Vero Beach, Florida, United States
      • Boehringer Ingelheim Investigational Site
  • Georgia
    • Atlanta, Georgia, United States
      • Boehringer Ingelheim Investigational Site
    • Macon, Georgia, United States
      • Mercer University School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States
      • University of Kentucky Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States
      • Boehringer Ingelheim Investigational Site
    • Springfield, Massachusetts, United States
      • Boehringer Ingelheim Investigational Site
  • Michigan
    • Detroit, Michigan, United States
      • Henry Ford Hospital
  • New Mexico
    • Santa Fe, New Mexico, United States
      • Boehringer Ingelheim Investigational Site
  • New York
    • Albany, New York, United States
      • Albany Medical College
    • New York, New York, United States
      • Boehringer Ingelheim Investigational Site
    • Stony Brook, New York, United States
      • University of New York, Stony Brook
  • North Carolina
    • Durham, North Carolina, United States
      • Duke University Medical Center
    • Huntersville, North Carolina, United States
      • Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States
      • UT Southwestern
    • Houston, Texas, United States
      • Boehringer Ingelheim Investigational Site
  • Virginia
    • Annandale, Virginia, United States
      • Boehringer Ingelheim Investigational Site
  • Washington
    • Tacoma, Washington, United States
      • Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim Study Coordinator, Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2003
• Primary Completion (Actual): January 27, 2004

Study Registration Dates

• First Submitted: March 19, 2003
• First Submitted That Met QC Criteria: March 20, 2003
• First Posted (Estimated): March 21, 2003

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Ritonavir; Lopinavir; Tipranavir; Amprenavir; Saquinavir
• Other Study ID Numbers: 1182.51