Dose Ranging Trial of Tipranavir/Ritonavir in Treatment-Experienced HIV Infected Individuals

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00034866
First received: May 2, 2002
Last updated: September 19, 2005
Last verified: September 2005
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Protease inhibitor tipranavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Estimated Enrollment: 165
Study Start Date: April 2002
Estimated Study Completion Date: October 2002
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent prior to trial participation.
  2. HIV-1 infected males or females >= 18 years of age.
  3. At least 3 months experience taking NRTIs, NNRTI(s), and PIs.
  4. Current PI-based 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.
  5. HIV-1 viral load >= 1000 copies/mL at screening.
  6. Genotypic resistance report indicating one or more primary PI resistance mutation(s), including 30N, 46I/L, 48V, 50V, 82A/F/T, 84V or 90M, with not more than one of 82 A/F/T or 84V or 90M.
  7. 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 GGT, Grade 2 cholesterol or triglycerides, and no higher than Grade 1 for all other tests based on the DAIDS Grading Scale. All laboratory values outside these limits are subject to approval by BI.
  8. Acceptable medical history, as assessed by the investigator, with chest X-ray and ECG within 1 year of study participation.
  9. Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system, such as: grapefruit or Seville oranges or their products; herbal preparations containing St. John’s Wort or milk thistle, and garlic supplements.
  10. A prior AIDS defining event is acceptable as long as it has resolved or the subject has been on stable treatment for at least 2 months.

Exclusion Criteria:

  1. ARV medication naïve.
  2. 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 barrier methods of contraception (e.g. latex condom plus spermicidal jelly/foam).
  3. Any active opportunistic infection within 60 days before study entry.
  4. Active Hepatitis B or C disease defined as HBsAg positive or HCV RNA positive with AST/ALT >Grade 1.
  5. Prior tipranavir use.
  6. 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.
  7. Use of concomitant drugs which may significantly reduce plasma levels of the study medications.
  8. Use of immunomodulatory drugs (e.g. interferon, cyclosporin, hydroxyurea, interleukin-2).
  9. Active substance abuse.
  10. Inability to swallow TPV or RTV capsules.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00034866

  Show 51 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00034866     History of Changes
Other Study ID Numbers: BI 1182.52
Study First Received: May 2, 2002
Last Updated: September 19, 2005
Health Authority: United States: Food and Drug Administration

Keywords provided by Boehringer Ingelheim:
HIV
treatment experienced
Boehringer
tipranavir
ritonavir

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protease Inhibitors
Ritonavir
HIV Protease Inhibitors
Tipranavir
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014