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

HIV Infections Clinical Trial

Official title:

SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavi/r IN Race/Gender HIV+ Patients Randomized to Therapeutic Drug Monitoring or Standard of Care

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00440271
• Other study ID #: 1182.98
• Secondary ID: EudraCT No.: 200
• Status: Terminated
• Phase: Phase 3
• First received: February 26, 2007
• Last updated: June 17, 2014
• Start date: February 2007

Study information

• Verified date: January 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: A.N.M.A.T. (Administracion Nacional de Medicamentos, Alimentos Y Tecnología)Brazil: ANVISACanada: Therapeutic Products DirectorateGermany: Bundesinstitut für Arzneimittel und MedizinprodukteItaly: Comitato Etico della Fondazione Centro S. Raffaele del Monte Tabor (IRCCS) - MilanoSpain:United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 33
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• tipranavir

• ritonavir

• 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.

Locations

Country	Name	City	State
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
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
Canada	1182.98.1007 Boehringer Ingelheim Investigational Site	Quebec, Ste Foy	Quebec
Germany	1182.98.4903 Boehringer Ingelheim Investigational Site	Bochum
Germany	1182.98.4908 Boehringer Ingelheim Investigational Site	Hamburg
Italy	1182.98.3907 Boehringer Ingelheim Investigational Site	Torino
Spain	1182.98.3402	Barcelona
Spain	1182.98.3405	Madrid
Spain	1182.98.3406	Madrid
United States	1182.98.006 Boehringer Ingelheim Investigational Site	Akron	Ohio
United States	1182.98.023 Boehringer Ingelheim Investigational Site	Austin	Texas
United States	1182.98.007 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio
United States	1182.98.018 Boehringer Ingelheim Investigational Site	Clearwater	Florida
United States	1182.98.004 Boehringer Ingelheim Investigational Site	Decatur	Georgia
United States	1182.98.014 Boehringer Ingelheim Investigational Site	Fort Lauderdale	Florida
United States	1182.98.009 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1182.98.040 Boehringer Ingelheim Investigational Site	Huntersville	North Carolina
United States	1182.98.002 Boehringer Ingelheim Investigational Site	Kansas City	Missouri
United States	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	1182.98.020 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma
United States	1182.98.041 Boehringer Ingelheim Investigational Site	Orlando	Florida
United States	1182.98.029 Boehringer Ingelheim Investigational Site	Philadelphia	Pennsylvania
United States	1182.98.034 Boehringer Ingelheim Investigational Site	Stony Brook	New York
United States	1182.98.033 Boehringer Ingelheim Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Response at Week 48	percentage of participants whose viral load <50 copies/mL at Week 48	after 48 weeks of treatment	No
Secondary	Percentage of Participants Whose Viral Load <50 Copies/mL at Each Visit Including Visits at Weeks 24 and 48		after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)	No
Secondary	Percentage of Participants Whose Viral Load <400 Copies/mL at Each Visit Including Visits at Weeks 24 and 48		after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)	No
Secondary	Percentage of Participants Whose =1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48		after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)	No
Secondary	Change in Viral Load From Baseline at Each Visit		after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)	No
Secondary	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.	after Day 1 of treatment	No
Secondary	Time to New AIDS or AIDS Related Progression Event or Death		after Day 1 of treatment	No
Secondary	Change in CD4+ and CD8+ Cell Counts From Baseline at Each Visit Including Visits at Week 24 and Week 48		after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)	No
Secondary	Change in Ratio of CD38+/CD8+ From Baseline to Week 48		after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)	No
Secondary	Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48		after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)	No
Secondary	Patients Adherence With Study Medication Based on Pill Count		after 4 weeks of treatment	No
Secondary	Occurrence of TPV Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured		after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)	No
Secondary	Occurrence of TPV Trough Concentration >120 µM		after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)	No
Secondary	Post-dose TPV and RTV Concentrations at Week 4		Week 4	No

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