Back to resultsSPRING: Safety, Efficacy, Pharmacokinetics of tipRanavir/r IN Race/Gender HIV+ Patients Randomized to TDM or SoC
Primary Purpose
HIV Infections
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
tipranavir
ritonavir
Optimized Background Regimen (OBR)
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections
Eligibility Criteria
Inclusion Criteria:
Main inclusion criteria for the study are:
- HIV-1 infected adults, men and women at least 18 years of age.
- 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.
- CD4+ T lymphocyte count >=50 cells/mm3.
- HIV-1 viral load >=1,000 copies/mL at screening.
- 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.
- Acceptable screening laboratory values that indicate adequate baseline organ function.
- 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.
- 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:
- Known hypersensitivity to the tipranavir (TPV) or ritonavir (RTV).
- ARV medication naïve.
- Genotypic resistance to TPV (defined as a TPV mutation score >7).
- Patients on recent drug holiday, defined as off antiretroviral (ARV) medications for at least 7 consecutive days within the month prior to screening.
- Prior tipranavir use.
- Inability to adhere to the requirements of the protocol.
- Patients with prior history of hemorrhagic stroke or intracranial aneurysm.
- Patients with a history of ischemic stroke, neurosurgery or skull trauma within 4 weeks prior to screening.
- History of Progressive Multifocal Leukoencephalopathy, Visceral Kaposi's Sarcoma, and/or any malignancy.
- Any acquired immunodeficiency syndrome (AIDS) defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit.
Sites / Locations
- 1182.98.033 Boehringer Ingelheim Investigational Site
- 1182.98.018 Boehringer Ingelheim Investigational Site
- 1182.98.014 Boehringer Ingelheim Investigational Site
- 1182.98.041 Boehringer Ingelheim Investigational Site
- 1182.98.004 Boehringer Ingelheim Investigational Site
- 1182.98.002 Boehringer Ingelheim Investigational Site
- 1182.98.016 Boehringer Ingelheim Investigational Site
- 1182.98.026 Boehringer Ingelheim Investigational Site
- 1182.98.034 Boehringer Ingelheim Investigational Site
- 1182.98.040 Boehringer Ingelheim Investigational Site
- 1182.98.006 Boehringer Ingelheim Investigational Site
- 1182.98.007 Boehringer Ingelheim Investigational Site
- 1182.98.020 Boehringer Ingelheim Investigational Site
- 1182.98.029 Boehringer Ingelheim Investigational Site
- 1182.98.023 Boehringer Ingelheim Investigational Site
- 1182.98.009 Boehringer Ingelheim Investigational Site
- 1182.98.5405 CENTRO de INFECTOLOGIA y ASISTENCIA (CIAS)
- 1182.98.5403 Centro Hospital Higa - Dr Oscar Alende
- 1182.98.5402 Caici
- 1182.98.55002 Hospital DIA
- 1182.98.55004 Unidade de Referência em doenças Infecciosas Preveníveis
- 1182.98.55001 Universidade Federal de Sao Paulo
- 1182.98.55003 Centro de Referência e Treinamento - DST/AIDS
- 1182.98.1007 Boehringer Ingelheim Investigational Site
- 1182.98.4903 Boehringer Ingelheim Investigational Site
- 1182.98.4908 Boehringer Ingelheim Investigational Site
- 1182.98.3907 Boehringer Ingelheim Investigational Site
- 1182.98.3402
- 1182.98.3405
- 1182.98.3406
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Standard of Care (SoC)
Therapeutic Drug Monitoring (TDM)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Treatment Response at Week 48
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
Percentage of Participants Whose Viral Load <400 Copies/mL at Each Visit Including Visits at Weeks 24 and 48
Percentage of Participants Whose ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48
Change in Viral Load From Baseline at Each Visit
Time to Treatment Failure
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
Change in CD4+ and CD8+ Cell Counts From Baseline at Each Visit Including Visits at Week 24 and Week 48
Change in Ratio of CD38+/CD8+ From Baseline to Week 48
Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
Patients Adherence With Study Medication Based on Pill Count
Occurrence of TPV Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured
Occurrence of TPV Trough Concentration >120 μM
Post-dose TPV and RTV Concentrations at Week 4
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00440271
Brief Title
SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavir/r IN Race/Gender HIV+ Patients Randomized to TDM or SoC
Official Title
SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavi/r IN Race/Gender HIV+ Patients Randomized to Therapeutic Drug Monitoring or Standard of Care
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Terminated
Study Start Date
February 2007 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
The primary purpose of this study is to:
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.
Determine pharmacokinetic data in this racially and gender diverse population.
Determine the potential utility of using therapeutic drug monitoring (TDM) in improving efficacy outcomes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standard of Care (SoC)
Arm Type
Other
Arm Description
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.
Arm Title
Therapeutic Drug Monitoring (TDM)
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
tipranavir
Intervention Type
Drug
Intervention Name(s)
ritonavir
Intervention Type
Drug
Intervention Name(s)
Optimized Background Regimen (OBR)
Other Intervention Name(s)
Nucleoside Reverse Transcriptase Inhibitors (NRTIs),, Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs),, Enfuvirtide,, Maraviroc,, Raltegravir
Intervention Description
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.
Primary Outcome Measure Information:
Title
Treatment Response at Week 48
Description
percentage of participants whose viral load <50 copies/mL at Week 48
Time Frame
after 48 weeks of treatment
Secondary Outcome Measure Information:
Title
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)
Title
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)
Title
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)
Title
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)
Title
Time to Treatment Failure
Description
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 Frame
after Day 1 of treatment
Title
Time to New AIDS or AIDS Related Progression Event or Death
Time Frame
after Day 1 of treatment
Title
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)
Title
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)
Title
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)
Title
Patients Adherence With Study Medication Based on Pill Count
Time Frame
after 4 weeks of treatment
Title
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)
Title
Occurrence of TPV Trough Concentration >120 μM
Time Frame
after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Title
Post-dose TPV and RTV Concentrations at Week 4
Time Frame
Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Main inclusion criteria for the study are:
HIV-1 infected adults, men and women at least 18 years of age.
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.
CD4+ T lymphocyte count >=50 cells/mm3.
HIV-1 viral load >=1,000 copies/mL at screening.
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.
Acceptable screening laboratory values that indicate adequate baseline organ function.
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.
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:
Known hypersensitivity to the tipranavir (TPV) or ritonavir (RTV).
ARV medication naïve.
Genotypic resistance to TPV (defined as a TPV mutation score >7).
Patients on recent drug holiday, defined as off antiretroviral (ARV) medications for at least 7 consecutive days within the month prior to screening.
Prior tipranavir use.
Inability to adhere to the requirements of the protocol.
Patients with prior history of hemorrhagic stroke or intracranial aneurysm.
Patients with a history of ischemic stroke, neurosurgery or skull trauma within 4 weeks prior to screening.
History of Progressive Multifocal Leukoencephalopathy, Visceral Kaposi's Sarcoma, and/or any malignancy.
Any acquired immunodeficiency syndrome (AIDS) defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1182.98.033 Boehringer Ingelheim Investigational Site
City
Washington
State/Province
District of Columbia
Country
United States
Facility Name
1182.98.018 Boehringer Ingelheim Investigational Site
City
Clearwater
State/Province
Florida
Country
United States
Facility Name
1182.98.014 Boehringer Ingelheim Investigational Site
City
Fort Lauderdale
State/Province
Florida
Country
United States
Facility Name
1182.98.041 Boehringer Ingelheim Investigational Site
City
Orlando
State/Province
Florida
Country
United States
Facility Name
1182.98.004 Boehringer Ingelheim Investigational Site
City
Decatur
State/Province
Georgia
Country
United States
Facility Name
1182.98.002 Boehringer Ingelheim Investigational Site
City
Kansas City
State/Province
Missouri
Country
United States
Facility Name
1182.98.016 Boehringer Ingelheim Investigational Site
City
New York
State/Province
New York
Country
United States
Facility Name
1182.98.026 Boehringer Ingelheim Investigational Site
City
New York
State/Province
New York
Country
United States
Facility Name
1182.98.034 Boehringer Ingelheim Investigational Site
City
Stony Brook
State/Province
New York
Country
United States
Facility Name
1182.98.040 Boehringer Ingelheim Investigational Site
City
Huntersville
State/Province
North Carolina
Country
United States
Facility Name
1182.98.006 Boehringer Ingelheim Investigational Site
City
Akron
State/Province
Ohio
Country
United States
Facility Name
1182.98.007 Boehringer Ingelheim Investigational Site
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
1182.98.020 Boehringer Ingelheim Investigational Site
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
1182.98.029 Boehringer Ingelheim Investigational Site
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
1182.98.023 Boehringer Ingelheim Investigational Site
City
Austin
State/Province
Texas
Country
United States
Facility Name
1182.98.009 Boehringer Ingelheim Investigational Site
City
Houston
State/Province
Texas
Country
United States
Facility Name
1182.98.5405 CENTRO de INFECTOLOGIA y ASISTENCIA (CIAS)
City
Capital Federal ,Buenos Aires
Country
Argentina
Facility Name
1182.98.5403 Centro Hospital Higa - Dr Oscar Alende
City
Mar del Plata
Country
Argentina
Facility Name
1182.98.5402 Caici
City
Rosario
Country
Argentina
Facility Name
1182.98.55002 Hospital DIA
City
Sacomã - São Paulo
Country
Brazil
Facility Name
1182.98.55004 Unidade de Referência em doenças Infecciosas Preveníveis
City
Santo André
Country
Brazil
Facility Name
1182.98.55001 Universidade Federal de Sao Paulo
City
Sao Paulo
Country
Brazil
Facility Name
1182.98.55003 Centro de Referência e Treinamento - DST/AIDS
City
Vila Mariana - Sao Paulo
Country
Brazil
Facility Name
1182.98.1007 Boehringer Ingelheim Investigational Site
City
Quebec, Ste Foy
State/Province
Quebec
Country
Canada
Facility Name
1182.98.4903 Boehringer Ingelheim Investigational Site
City
Bochum
Country
Germany
Facility Name
1182.98.4908 Boehringer Ingelheim Investigational Site
City
Hamburg
Country
Germany
Facility Name
1182.98.3907 Boehringer Ingelheim Investigational Site
City
Torino
Country
Italy
Facility Name
1182.98.3402
City
Barcelona
Country
Spain
Facility Name
1182.98.3405
City
Madrid
Country
Spain
Facility Name
1182.98.3406
City
Madrid
Country
Spain
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1182/1182.98_U09-3280-01-DS.pdf
Description
Related Info
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1182/1182.98_statement.pdf
Description
Related Info
Learn more about this trial
SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavir/r IN Race/Gender HIV+ Patients Randomized to TDM or SoC
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