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

This study has been terminated.
Sponsor:
Information provided by:
Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00440271
First received: February 26, 2007
Last updated: May 18, 2012
Last verified: May 2012
History of Changes
  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
 Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

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
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Standard of Care (SoC) Drug: tipranavir Drug: ritonavir
Therapeutic Drug Monitoring (TDM) Drug: tipranavir Drug: ritonavir

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00440271

  Show 30 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim Pharmaceuticals
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals
  More Information

Additional Information:
Related Info  This link exits the ClinicalTrials.gov site
Related Info  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, 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
Results First Received: October 20, 2009
Last Updated: May 18, 2012
Health Authority: Argentina: A.N.M.A.T. (Administracion Nacional de Medicamentos, Alimentos Y Tecnología)
Brazil: ANVISA
Canada: Therapeutic Products Directorate
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Italy: Comitato Etico della Fondazione Centro S. Raffaele del Monte Tabor (IRCCS) - Milano
Spain:
United States: Food and Drug Administration

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
Ritonavir
 Tipranavir
HIV Protease Inhibitors
Protease Inhibitors
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 June 17, 2013