Clinical trial NCT00440271: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-02-27
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Treatment Response at Week 48
timeFrame: after 48 weeks of treatment
Secondary outcomes:
measure: Percentage of Participants Whose Viral Load <50 Copies/mL at Each Visit Including Visits at Weeks 24 and 48
timeFrame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
measure: Percentage of Participants Whose Viral Load <400 Copies/mL at Each Visit Including Visits at Weeks 24 and 48
timeFrame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
measure: Percentage of Participants Whose ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48
timeFrame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
measure: Change in Viral Load From Baseline at Each Visit
timeFrame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
measure: Time to Treatment Failure
timeFrame: after Day 1 of treatment
measure: Time to New AIDS or AIDS Related Progression Event or Death
timeFrame: after Day 1 of treatment
measure: Change in CD4+ and CD8+ Cell Counts From Baseline at Each Visit Including Visits at Week 24 and Week 48
timeFrame: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)
measure: Change in Ratio of CD38+/CD8+ From Baseline to Week 48
timeFrame: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)
measure: Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
timeFrame: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)
measure: Patients Adherence With Study Medication Based on Pill Count
timeFrame: after 4 weeks of treatment
measure: Occurrence of TPV Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured
timeFrame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
measure: Occurrence of TPV Trough Concentration >120 μM
timeFrame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
measure: Post-dose TPV and RTV Concentrations at Week 4
timeFrame: Week 4
Other outcomes:
Locations:
city: Washington
country: United States
facility: 1182.98.033 Boehringer Ingelheim Investigational Site
state: District of Columbia
city: Clearwater
country: United States
facility: 1182.98.018 Boehringer Ingelheim Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: 1182.98.014 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1182.98.041 Boehringer Ingelheim Investigational Site
state: Florida
city: Decatur
country: United States
facility: 1182.98.004 Boehringer Ingelheim Investigational Site
state: Georgia
city: Kansas City
country: United States
facility: 1182.98.002 Boehringer Ingelheim Investigational Site
state: Missouri
city: New York
country: United States
facility: 1182.98.016 Boehringer Ingelheim Investigational Site
state: New York
city: New York
country: United States
facility: 1182.98.026 Boehringer Ingelheim Investigational Site
state: New York
city: Stony Brook
country: United States
facility: 1182.98.034 Boehringer Ingelheim Investigational Site
state: New York
city: Huntersville
country: United States
facility: 1182.98.040 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Akron
country: United States
facility: 1182.98.006 Boehringer Ingelheim Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: 1182.98.007 Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: 1182.98.020 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: 1182.98.029 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Austin
country: United States
facility: 1182.98.023 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1182.98.009 Boehringer Ingelheim Investigational Site
state: Texas
city: Capital Federal ,Buenos Aires
country: Argentina
facility: 1182.98.5405 CENTRO de INFECTOLOGIA y ASISTENCIA (CIAS)
city: Mar del Plata
country: Argentina
facility: 1182.98.5403 Centro Hospital Higa - Dr Oscar Alende
city: Rosario
country: Argentina
facility: 1182.98.5402 Caici
city: Sacomã - São Paulo
country: Brazil
facility: 1182.98.55002 Hospital DIA
city: Santo André
country: Brazil
facility: 1182.98.55004 Unidade de Referência em doenças Infecciosas Preveníveis
city: Sao Paulo
country: Brazil
facility: 1182.98.55001 Universidade Federal de Sao Paulo
city: Vila Mariana - Sao Paulo
country: Brazil
facility: 1182.98.55003 Centro de Referência e Treinamento - DST/AIDS
city: Quebec, Ste Foy
country: Canada
facility: 1182.98.1007 Boehringer Ingelheim Investigational Site
state: Quebec
city: Bochum
country: Germany
facility: 1182.98.4903 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1182.98.4908 Boehringer Ingelheim Investigational Site
city: Torino
country: Italy
facility: 1182.98.3907 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1182.98.3402
city: Madrid
country: Spain
facility: 1182.98.3405
city: Madrid
country: Spain
facility: 1182.98.3406
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: