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Clinical Trials

MainTitle

SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavir/r IN Race/Gender HIV+ Patients Randomized to TDM or SoC

This study has been terminated
Sponsor
Boehringer Ingelheim


Information provided by (Responsible Party)
Boehringer Ingelheim
ClinicalTrials.gov Identifier
NCT00440271

First received: February 26, 2007
Last updated: June 17, 2014
Last Verified: January 2014
History of Changes
Purpose

Purpose

The primary purpose of this study is to:

  1. Demonstrate the safety and efficacy of tipranavir/ritonavir (TPV/r) among a racially diverse HIV+ population (males and females) who are three-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI)) experienced with documented resistance to more than one PI.
  2. Determine pharmacokinetic data in this racially and gender diverse population.
  3. Determine the potential utility of using therapeutic drug monitoring (TDM) in improving
efficacy outcomes.

Condition Intervention Phase
HIV Infections

Drug : tipranavir
Drug : ritonavir
Drug : Optimized Background Regimen (OBR)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavi/r IN Race/Gender HIV+ Patients Randomized to Therapeutic Drug Monitoring or Standard of Care

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures

  • Treatment Response at Week 48 [ Time Frame: after 48 weeks of treatment ]
    percentage of participants whose viral load <50 copies/mL at Week 48
Secondary Outcome Measures:
  • Percentage of Participants Whose Viral Load <50 Copies/mL at Each Visit Including Visits at Weeks 24 and 48 [ Time Frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48) ]
  • Percentage of Participants Whose Viral Load <400 Copies/mL at Each Visit Including Visits at Weeks 24 and 48 [ Time Frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48) ]
  • Percentage of Participants Whose ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48 [ Time Frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48) ]
  • Change in Viral Load From Baseline at Each Visit [ Time Frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48) ]
  • Time to Treatment Failure [ Time Frame: after Day 1 of treatment ]
    For patients who never achieve a confirmed virologic response, time to treatment failure is defined as 0. For patients who achieve a confirmed virologic response, time to treatment failure is the earliest time of either: death, permanent discontinuation of the study drug or loss to follow-up, introduction of a new anti-retroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background drug, but not the study drug, or first occurrence of a VL >50 copies/mL at two consecutive measurements after having achieved a VL <50 copies/mL.
  • Time to New AIDS or AIDS Related Progression Event or Death [ Time Frame: after Day 1 of treatment ]
  • Change in CD4+ and CD8+ Cell Counts From Baseline at Each Visit Including Visits at Week 24 and Week 48 [ Time Frame: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48) ]
  • Change in Ratio of CD38+/CD8+ From Baseline to Week 48 [ Time Frame: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48) ]
  • Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48 [ Time Frame: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48) ]
  • Patients Adherence With Study Medication Based on Pill Count [ Time Frame: after 4 weeks of treatment ]
  • Occurrence of TPV Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured [ Time Frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48) ]
  • Occurrence of TPV Trough Concentration >120 μM [ Time Frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48) ]
  • Post-dose TPV and RTV Concentrations at Week 4 [ Time Frame: Week 4 ]

Enrollment: 33
Study Start Date: February 2007
Estimated Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Other: Standard of Care (SoC)
Standard of Care (SOC) Arm = Tipranavir/ritonavir (TPV/r) capsules taken orally at a dose of 500 mg/200 mg twice a day (BID) plus optimized background regimen (OBR). No TPV/r dose changes were permitted.
Drug: tipranavir
Drug: ritonavir
Drug: Optimized Background Regimen (OBR)

Patients received between two and four active anti-retroviral medications based on resistance testing results, as background treatment, and remained on these for the duration of the trial.

Other Name:
  • Nucleoside Reverse Transcriptase Inhibitors (NRTIs),
  • Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs),
  • Enfuvirtide,
  • Maraviroc,
  • Raltegravir

Other: Therapeutic Drug Monitoring (TDM)
Therapeutic Drug Monitoring (TDM) Arm = Patients began by receiving standard of care (SOC) tipranavir/ritonavir (TPV/r) capsules orally at a dose of 500 mg/200 mg twice a day (BID) plus optimized background regimen (OBR) followed, if needed, by TPV or ritonavir (RTV) dose adjustments at Week 4, 6, 10, 14, 18, 22, 26 and 30 based on viral response, phenotypic inhibitory quotient (IQ), and TPV trough concentrations.
Drug: tipranavir
Drug: ritonavir
Drug: Optimized Background Regimen (OBR)

Patients received between two and four active anti-retroviral medications based on resistance testing results, as background treatment, and remained on these for the duration of the trial.

Other Name:
  • Nucleoside Reverse Transcriptase Inhibitors (NRTIs),
  • Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs),
  • Enfuvirtide,
  • Maraviroc,
  • Raltegravir

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:
Main inclusion criteria for the study are:

    1. HIV-1 infected adults, men and women at least 18 years of age.
    2. 3-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI)) treatment-experienced (min of 3-months duration for each class) with resistance to more than one PI (on screening resistance testing). NNRTI-naïve patients who have genotypically documented NNRTI-resistance mutations on past or screening resistance testing would be eligible.
    3. CD4+ T lymphocyte count >=50 cells/mm3.
    4. HIV-1 viral load >=1,000 copies/mL at screening.
    5. The antiretroviral (ARV) study treatment regimen must consist of TPV/r in combo with an optimized background regimen (OBR) of 2-4 agents: N(t)RTIs (NRTI or NtRTI), enfuvirtide (ENF), and/or, where available, a trial approved expanded access program (EAP) investigational agent.
    6. Acceptable screening laboratory values that indicate adequate baseline organ function.
    7. Acceptable medical history with a chest X-ray without evidence of active disease and an electrocardiogram (ECG) without clinically important abnormalities within one year of the study.
    8. A reliable method of barrier contraception will be used by all female patients who are of childbearing potential.


Exclusion Criteria:

    Main exclusion criteria for the study are:
    1. Known hypersensitivity to the tipranavir (TPV) or ritonavir (RTV).
    2. ARV medication naïve.
    3. Genotypic resistance to TPV (defined as a TPV mutation score >7).
    4. Patients on recent drug holiday, defined as off antiretroviral (ARV) medications for at least 7 consecutive days within the month prior to screening.
    5. Prior tipranavir use.
    6. Inability to adhere to the requirements of the protocol.
    7. Patients with prior history of hemorrhagic stroke or intracranial aneurysm.
    8. Patients with a history of ischemic stroke, neurosurgery or skull trauma within 4 weeks prior to screening.
    9. History of Progressive Multifocal Leukoencephalopathy, Visceral Kaposi's Sarcoma, and/or any malignancy.
    10. Any acquired immunodeficiency syndrome (AIDS) defining illness that is unresolved,
    symptomatic or not stable on treatment for at least 12 weeks at screening visit.

    contacts and locations

    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: NCT00440271

    Locations

    United States, District of Columbia
    1182.98.033 Boehringer Ingelheim Investigational Site
    Washington, District of Columbia, United States
    United States, Florida
    1182.98.018 Boehringer Ingelheim Investigational Site
    Clearwater, Florida, United States
    1182.98.014 Boehringer Ingelheim Investigational Site
    Fort Lauderdale, Florida, United States
    1182.98.041 Boehringer Ingelheim Investigational Site
    Orlando, Florida, United States
    United States, Georgia
    1182.98.004 Boehringer Ingelheim Investigational Site
    Decatur, Georgia, United States
    United States, Missouri
    1182.98.002 Boehringer Ingelheim Investigational Site
    Kansas City, Missouri, United States
    United States, New York
    1182.98.016 Boehringer Ingelheim Investigational Site
    New York, New York, United States
    1182.98.026 Boehringer Ingelheim Investigational Site
    New York, New York, United States
    1182.98.034 Boehringer Ingelheim Investigational Site
    Stony Brook, New York, United States
    United States, North Carolina
    1182.98.040 Boehringer Ingelheim Investigational Site
    Huntersville, North Carolina, United States
    United States, Ohio
    1182.98.006 Boehringer Ingelheim Investigational Site
    Akron, Ohio, United States
    1182.98.007 Boehringer Ingelheim Investigational Site
    Cincinnati, Ohio, United States
    United States, Oklahoma
    1182.98.020 Boehringer Ingelheim Investigational Site
    Oklahoma City, Oklahoma, United States
    United States, Pennsylvania
    1182.98.029 Boehringer Ingelheim Investigational Site
    Philadelphia, Pennsylvania, United States
    United States, Texas
    1182.98.023 Boehringer Ingelheim Investigational Site
    Austin, Texas, United States
    1182.98.009 Boehringer Ingelheim Investigational Site
    Houston, Texas, United States
    Argentina
    1182.98.5405 CENTRO de INFECTOLOGIA y ASISTENCIA (CIAS)
    Capital Federal ,Buenos Aires, Argentina
    1182.98.5403 Centro Hospital Higa - Dr Oscar Alende
    Mar del Plata, Argentina
    1182.98.5402 Caici
    Rosario, Argentina
    Brazil
    1182.98.55002 Hospital DIA
    Sacomã - São Paulo, Brazil
    1182.98.55004 Unidade de Referência em doenças Infecciosas Preveníveis
    Santo André, Brazil
    1182.98.55001 Universidade Federal de Sao Paulo
    Sao Paulo, Brazil
    1182.98.55003 Centro de Referência e Treinamento - DST/AIDS
    Vila Mariana - Sao Paulo, Brazil
    Canada
    1182.98.1007 Boehringer Ingelheim Investigational Site
    Quebec, Ste Foy, Quebec, Canada
    Germany
    1182.98.4903 Boehringer Ingelheim Investigational Site
    Bochum, Germany
    1182.98.4908 Boehringer Ingelheim Investigational Site
    Hamburg, Germany
    Italy
    1182.98.3907 Boehringer Ingelheim Investigational Site
    Torino, Italy
    Spain
    1182.98.3402
    Barcelona, Spain
    1182.98.3405
    Madrid, Spain
    1182.98.3406
    Madrid, Spain

    Sponsors and Collaborators

    Boehringer Ingelheim

    Investigators

    Study Chair: Boehringer Ingelheim Boehringer Ingelheim
    More Information

    More Information


    Responsible Party: Boehringer Ingelheim  
    ClinicalTrials.gov Identifier: NCT00440271   History of Changes  
    Other Study ID Numbers: 1182.98  
      EudraCT No.: 2005-005264-86  
    Study First Received: February 26, 2007  
    Last Updated: June 17, 2014  

    Additional relevant MeSH terms:
    HIV Infections
    Ritonavir
    Tipranavir
    Reverse Transcriptase Inhibitors

    ClinicalTrials.gov processed this data on October 23, 2017
    This information is provided by ClinicalTrials.gov.