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

NCT00440271 | Terminated Phase 3 Results

• 2 other identifiers: 1182.98EudraCT No.: 2005-005264-86
• Study Type: interventional
• Target: 33
• Locations: 7 countries
• Sites: 30

Brief Summary

The primary purpose of this study is to:

1. 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. 2.Determine pharmacokinetic data in this racially and gender diverse population.
3. 3.Determine the potential utility of using therapeutic drug monitoring (TDM) in improving efficacy outcomes.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Treatment Response at Week 48

  percentage of participants whose viral load \<50 copies/mL at Week 48

  after 48 weeks of treatment

Secondary Outcomes (13)

• 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)

• 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)

• 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)

• Change in Viral Load From Baseline at Each Visit

  after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)

• Time to Treatment Failure

  after Day 1 of treatment

Study Arms (2)

Standard of Care (SoC)

OTHER

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)

Therapeutic Drug Monitoring (TDM)

OTHER

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)

Interventions

tipranavir DRUG

Standard of Care (SoC); Therapeutic Drug Monitoring (TDM)

ritonavir DRUG

Standard of Care (SoC); Therapeutic Drug Monitoring (TDM)

Optimized Background Regimen (OBR) DRUG

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.

Also known as: Nucleoside Reverse Transcriptase Inhibitors (NRTIs),, Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs),, Enfuvirtide,, Maraviroc,, Raltegravir

Standard of Care (SoC); Therapeutic Drug Monitoring (TDM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infected adults, men and women at least 18 years of age.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (30)

1182.98.033 Boehringer Ingelheim Investigational Site

Washington D.C., District of Columbia, United States

Location

1182.98.018 Boehringer Ingelheim Investigational Site

Clearwater, Florida, United States

Location

1182.98.014 Boehringer Ingelheim Investigational Site

Fort Lauderdale, Florida, United States

Location

1182.98.041 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

Location

1182.98.004 Boehringer Ingelheim Investigational Site

Decatur, Georgia, United States

Location

1182.98.002 Boehringer Ingelheim Investigational Site

Kansas City, Missouri, United States

Location

1182.98.016 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1182.98.026 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1182.98.034 Boehringer Ingelheim Investigational Site

Stony Brook, New York, United States

Location

1182.98.040 Boehringer Ingelheim Investigational Site

Huntersville, North Carolina, United States

Location

1182.98.006 Boehringer Ingelheim Investigational Site

Akron, Ohio, United States

Location

1182.98.007 Boehringer Ingelheim Investigational Site

Cincinnati, Ohio, United States

Location

1182.98.020 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

1182.98.029 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

Location

1182.98.023 Boehringer Ingelheim Investigational Site

Austin, Texas, United States

Location

1182.98.009 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1182.98.5405 CENTRO de INFECTOLOGIA y ASISTENCIA (CIAS)

Capital Federal ,Buenos Aires, Argentina

Location

1182.98.5403 Centro Hospital Higa - Dr Oscar Alende

Mar del Plata, Argentina

Location

1182.98.5402 Caici

Rosario, Argentina

Location

1182.98.55002 Hospital DIA

Sacomã - São Paulo, Brazil

Location

1182.98.55004 Unidade de Referência em doenças Infecciosas Preveníveis

Santo André, Brazil

Location

1182.98.55001 Universidade Federal de Sao Paulo

São Paulo, Brazil

Location

1182.98.55003 Centro de Referência e Treinamento - DST/AIDS

Vila Mariana - Sao Paulo, Brazil

Location

1182.98.1007 Boehringer Ingelheim Investigational Site

Quebec, Ste Foy, Quebec, Canada

Location

1182.98.4903 Boehringer Ingelheim Investigational Site

Bochum, Germany

Location

1182.98.4908 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1182.98.3907 Boehringer Ingelheim Investigational Site

Torino, Italy

Location

1182.98.3402

Barcelona, Spain

Location

1182.98.3405

Madrid, Spain

Location

1182.98.3406

Madrid, Spain

Location

MeSH Terms

Conditions

HIV Infections

Interventions

tipranavir; Ritonavir; Enfuvirtide; Maraviroc; Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; HIV Envelope Protein gp41; Viral Fusion Proteins; Membrane Fusion Proteins; Membrane Proteins; Proteins; HIV Antigens; Antigens, Viral; Viral Proteins; env Gene Products, Human Immunodeficiency Virus; Gene Products, env; Retroviridae Proteins; Human Immunodeficiency Virus Proteins; Viral Envelope Proteins; Viral Structural Proteins; Antigens; Biological Factors; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Pyrrolidinones; Pyrrolidines

Limitations and Caveats

The study was terminated early due to low patient enrollment, and, therefore, no analysis was performed on the primary and secondary endpoints

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2007
• First Posted: February 27, 2007
• Study Start: February 1, 2007
• Primary Completion: October 1, 2008
• Last Updated: June 27, 2014
• Results First Posted: November 26, 2009

Record last verified: 2014-01

Locations

AR (3); BR (4); CA (1); IT (1); US (16); DE (2); ES (3)