Safety and Antiviral Activity of TPV in HCV and/or HBV HIV Coinfected Patients TDM Randomised Pilot Evaluation

NCT00447902 | Terminated Phase 3 Results

• 2 other identifiers: 1182.99EudraCT No.: 2005-005023-33
• Study Type: interventional
• Target: 11
• Locations: 7 countries
• Sites: 30

Brief Summary

The main purposes of this study are: demonstrate the safety and efficacy of TPV/r among HCV or hepatitis B virus (HBV) co-infected HIV+population, three-class (NRTI, NNRTI, and PI) experienced, with documented resistance to more than one PI. Determine pharmacokinetic data in this co-infected population and potential utility of using therapeutic drug monitoring (TDM) in improving efficacy outcomes.

Conditions

HIV Infections

Keywords

treatment experienced

Outcome Measures

Primary Outcomes (2)

• Treatment Response at Week 48

  Treatment response is a confirmed virologic response, defined as a viral load less than 50 copies/mL at two consecutive measurements at least 5 days apart, without death, permanent discontinuation, or introduction of a new antiretroviral

  48 weeks

• The Primary Safety Endpoint Was the Occurrence of Dose-limiting Hepatotoxicity During the Study.

  Dose-limiting hepatotoxicity was defined as Grade 4 ALT or AST elevation confirmed in 48h or any evocative symptoms or signs of hepatitis, if it not clearly attributable to another cause. Patients who experienced dose-limiting hepatotoxicity stopped TPV/r and were considered treatment failures for the analysis.

  From the start of the study through 48 weeks.

Secondary Outcomes (16)

• Virologic Response Defined as Viral Load <50 Copies/mL at Each Visit

  After 4 weeks of treatment until the end of the trial

• Occurrence of Viral Load Less Than 400 Copies/mL at Weeks 24 and 48

  24 and 48 weeks

• Occurrence of Viral Load Less Than 400 Copies/mL at Each Visit

  After 4 weeks of treatment until the end of the trial

• Occurrence of ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48

  Baseline, 24 and 48 weeks

• Change in Viral Load From Baseline at Each Visit

  After 4 weeks of treatment until the end of the trial

Interventions

tipranavir DRUG

ritonavir DRUG

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 males or females at least 18 years of age.
• Three-class (Nucleoside reverse transcriptase inhibitor (NRTI), Non nucleoside reverse transcriptase inhibitor (NNRTI), and Protease inhibitor (PI)) treatment-experienced (a minimum of 3-months duration for each class) with resistance to more than one PI (on the screening resistance testing). Patients that are NNRTI-naïve patients but who have genotypically documented NNRTI-resistance mutations on past or screening resistance testing would be eligible.
• CD4+ T lymphocyte count ≥50 cells/µl and HIV-1 VL ≥1000 copies/mL at screening.
• The ARV study treatment regimen must consist of new TPV/r in combination with an OBR of 2-4 agents of the following: N(t)RTIs (NRTI or NtRTI), enfuvirtide (ENF), and/or, where available, an Expanded Access Program (EAP) investigational agent (Section 3.3). In total, patients are to have an ARV study treatment regimen consisting of at least 3 agents (TPV/r and two OBRs).
• Chronic hepatitis C Virus (HCV) infection demonstrated by HCV-ribonucleic acid (RNA) positivity or, Chronic hepatitis B (HB) infection demonstrated by anti HBc IgG Antibody and HB Surface Antigen positivity.
• Acceptable screening laboratory values that indicate adequate baseline organ function.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< Division of AIDS (DAIDS) Grade 3.
• Acceptable medical history, as assessed by the investigator.
• Any AIDS defining illness listed in the Appendix 10.3.1 should be accepted as long as is resolved, asymptomatic or stable on treatment for at least 12 weeks before screening (Visit 1); the AIDS defining events listed below are not acceptable History of Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any malignancy.
• A reliable method of barrier contraception will be used by all female patients who are of reproductive potential, for at least three months prior to Visit 3, during the trial, and 30 days after completion or termination from the trial.
• Karnofsky performance score ≥70.

You may not qualify if:

• Prior tipranavir use.
• Known hypersensitivity to any of the ingredients to the tipranavir or ritonavir formulations.
• ARV medication naive.
• Genotypic resistance to Tipranavir (TPV) (defined as a TPV mutation score of more than 7).
• Patients on recent drug holiday, defined as off ARV medications for at least 7 consecutive days within the month prior to screening.
• Decompensated liver disease, including presence or history of ascites, variceal bleeding, or hepatic encephalopathy or having ever been diagnosed as having hepatic insufficiency of Child Pugh class B or C.
• Female patients of childbearing potential who:
• have a positive serum pregnancy test at screening,
• are breast feeding,
• are planning to become pregnant,
• are not willing to use a barrier method of contraception, or
• are only willing to use an estrogen-containing medication, e.g., ethinyl estradiol, as a method of contraception.
• Use of concomitant drugs that may significantly reduce plasma levels of the study medications.
• Use of immunomodulatory drugs or antineoplastic agents within 30 days before study entry or during the trial.
• Inability to adhere to the requirements of the protocol, including active substance abuse, as defined by the investigator.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (30)

1182.99.32 Boehringer Ingelheim Investigational Site

Beverly Hills, California, United States

Location

1182.99.31 Boehringer Ingelheim Investigational Site

Fort Lauderdale, Florida, United States

Location

1182.99.12 Boehringer Ingelheim Investigational Site

Providence, Rhode Island, United States

Location

1182.99.1 Boehringer Ingelheim Investigational Site

Austin, Texas, United States

Location

1182.99.4 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1182.99.54001

Capital Federal, Argentina

Location

1182.99.55002 Hospital DIA

Sacomã - São Paulo, Brazil

Location

1182.99.55004 Unidade de Referência em doenças Infecciosas Preveníveis

Santo André, Brazil

Location

1182.99.55001 Universidade Federal de Sao Paulo

São Paulo, Brazil

Location

1182.99.55003 Centro de Referência e Treinamento - DST/AIDS

Vila Mariana - Sao Paulo, Brazil

Location

1182.99.3301A Boehringer Ingelheim Investigational Site

Garches, France

Location

1182.99.3306G Boehringer Ingelheim Investigational Site

Nantes, France

Location

1182.99.3306K Boehringer Ingelheim Investigational Site

Nantes, France

Location

1182.99.3310C Boehringer Ingelheim Investigational Site

Nice, France

Location

1182.99.3310D Boehringer Ingelheim Investigational Site

Nice, France

Location

1182.99.3310E Boehringer Ingelheim Investigational Site

Nice, France

Location

1182.99.3310F Boehringer Ingelheim Investigational Site

Nice, France

Location

1182.99.3310G Boehringer Ingelheim Investigational Site

Nice, France

Location

1182.99.3310H Boehringer Ingelheim Investigational Site

Nice, France

Location

1182.99.3304A Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.99.3304C Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.99.3302A Boehringer Ingelheim Investigational Site

Perpignan, France

Location

1182.99.4909 Boehringer Ingelheim Investigational Site

Düsseldorf, Germany

Location

1182.99.3912 Boehringer Ingelheim Investigational Site

Ancona, Italy

Location

1182.99.3901 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1182.99.3911 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1182.99.3916 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1182.99.3906 Boehringer Ingelheim Investigational Site

Pavia, Italy

Location

1182.99.3402

Barcelona, Spain

Location

1182.99.3407

Madrid, Spain

Location

MeSH Terms

Conditions

HIV Infections

Interventions

tipranavir; Ritonavir

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

Limitations and Caveats

Due to an early termination of the trial no analysis has been performed for 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 14, 2007
• First Posted: March 15, 2007
• Study Start: March 1, 2007
• Primary Completion: October 1, 2008
• Last Updated: May 14, 2014
• Results First Posted: December 23, 2009

Record last verified: 2014-04

Locations

ES (2); IT (5); AR (1); BR (4); FR (12); US (5); DE (1)