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 (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00440271
First received: February 26, 2007
Last updated: June 17, 2014
Last verified: January 2014
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Treatment Response at Week 48 [ Time Frame: after 48 weeks of treatment ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Time to Treatment Failure [ Time Frame: after Day 1 of treatment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Patients Adherence With Study Medication Based on Pill Count [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Occurrence of TPV Trough Concentration >120 μM [ Time Frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48) ] [ Designated as safety issue: No ]
  • Post-dose TPV and RTV Concentrations at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

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

  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
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

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

Additional Information:
No publications provided

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
Results First Received: October 20, 2009
Last Updated: June 17, 2014
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:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Reverse Transcriptase Inhibitors
Ritonavir
Tipranavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014