HIV InfectionsPhase 3NCT00447902
Safety and Antiviral Activity of TPV in HCV and/or HBV HIV Coinfected Patients TDM Randomised Pilot Evaluation
A Phase 3 study testing tipranavir and ritonavir in people with HIV Infections, run by Boehringer Ingelheim at 30 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- tipranavir and ritonavir
- How many people
- 11 participants
- Where
- 30 sitesin 7 countries
- Study dates
- Mar 2007to Oct 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
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- 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 investigational medications within 30 days before study entry or during the trial except for those investigational ARV drugs permitted during the trial as stated in inclusion criteria 6.
- 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.
- Anticipated need for an interferon-based regimen in the 48 weeks following the study entry.
- Any other or additional plausible cause for chronic liver disease, including the presence of other viruses known or suspected to cause hepatitis.
- Any active infection or neoplasm currently being treated.
- Patients with history of hemorrhagic stroke or intracranial aneurysm.
- Patients with history of ischemic stroke, neurosurgery, skull trauma and/or intracranial pathology (arteriovenous malformation, brain tumors and cerebral venous thrombosis) within 4 weeks prior to screening (Visit 1) as assessed by investigator.
- Patients with current history of alcohol abuse defined as alcohol consumption that would interfere with patient's compliance or result in biological abnormalities.
Trial locations and contacts
30 sites in 7 countries.
30 sites in 7 countries
France12 sites
1182.99.3301A Boehringer Ingelheim Investigational Site
Garches
1182.99.3306G Boehringer Ingelheim Investigational Site
Nantes
1182.99.3306K Boehringer Ingelheim Investigational Site
Nantes
1182.99.3310C Boehringer Ingelheim Investigational Site
Nice
1182.99.3310D Boehringer Ingelheim Investigational Site
Nice
1182.99.3310E Boehringer Ingelheim Investigational Site
Nice
1182.99.3310F Boehringer Ingelheim Investigational Site
Nice
1182.99.3310G Boehringer Ingelheim Investigational Site
Nice
1182.99.3310H Boehringer Ingelheim Investigational Site
Nice
1182.99.3304A Boehringer Ingelheim Investigational Site
Paris
1182.99.3304C Boehringer Ingelheim Investigational Site
Paris
1182.99.3302A Boehringer Ingelheim Investigational Site
Perpignan
United States5 sites
1182.99.1 Boehringer Ingelheim Investigational Site
Austin, Texas
1182.99.32 Boehringer Ingelheim Investigational Site
Beverly Hills, California
1182.99.31 Boehringer Ingelheim Investigational Site
Fort Lauderdale, Florida
1182.99.4 Boehringer Ingelheim Investigational Site
Houston, Texas
1182.99.12 Boehringer Ingelheim Investigational Site
Providence, Rhode Island
Italy5 sites
1182.99.3912 Boehringer Ingelheim Investigational Site
Ancona
1182.99.3901 Boehringer Ingelheim Investigational Site
Milan
1182.99.3911 Boehringer Ingelheim Investigational Site
Milan
1182.99.3916 Boehringer Ingelheim Investigational Site
Milan
1182.99.3906 Boehringer Ingelheim Investigational Site
Pavia
Brazil4 sites
1182.99.55002 Hospital DIA
Sacomã - São Paulo
1182.99.55004 Unidade de Referência em doenças Infecciosas Preveníveis
Santo André
1182.99.55001 Universidade Federal de Sao Paulo
São Paulo
1182.99.55003 Centro de Referência e Treinamento - DST/AIDS
Vila Mariana - Sao Paulo
Germany1 site
1182.99.4909 Boehringer Ingelheim Investigational Site
Düsseldorf
About this study
Official title: Safety and Antiviral Activity of TPV in Hepatitis C or Hepatitis B HIV Coinfected Patients - TDM Randomised Pilot Evaluation
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
- Being tested
- tipranavir, ritonavir
- Keywords
- treatment experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tipranavirDrug
ritonavirDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: From the start of the study through 48 weeks.
Secondary outcomes (16)
Virologic Response Defined as Viral Load <50 Copies/mL at Each Visit
Virologic response defined as viral load less than 50 copies/mL
Measured: 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
Patients with a viral load of less than 400 copies/mL at Weeks 24 and 48 as measured from a plasma sample.
Measured: 24 and 48 weeks
Occurrence of Viral Load Less Than 400 Copies/mL at Each Visit
Patients with a viral load of less than 400 copies/mL at each visit as measured from a plasma sample.
Measured: 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
Occurrence of greater than or equal to 1 log10 drop in viral load from baseline at all visits, including visits at Weeks 24 and 48
Measured: Baseline, 24 and 48 weeks
Change in Viral Load From Baseline at Each Visit
Change in viral load (measured from a plasma sample) from baseline at each visitPatients with a viral load of less than 400 copies/mL at each visit as .
Measured: After 4 weeks of treatment until the end of the trial
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.
Measured: After Day 1 of treatment until the end of the trial
Time to New AIDS or AIDS Related Progression Event or Death
Time to new AIDS or AIDS related progression event or death as defined by AIDS defining and/or AIDS-related illnesses.
Measured: After Day 1 of treatment until the end of the trial
Change in CD4+ and CD8+ Cell Counts From Baseline to Week 48
Change from baseline to Week 48 for CD4+ and CD8+ cell counts. Samples were obtained for CD4+ and CD8+ as measurements of viral suppression during antiretroviral therapy.
Measured: after 2 weeks of treatment till Week 48
Change in Ratio of CD38+/CD8+ From Baseline to Week 48
Change from baseline to Week 48 for the ratio of CD38+ to CD8+ cell counts. Samples were obtained for CD38+ and CD8+ as measurements of viral suppression during antiretroviral therapy.
Measured: after 2 weeks of treatment till Week 48
Change in Ratio of CD3+ CD8+ CD38+ HLA DR From Baseline to Week 48.
Change from baseline to Week 48 for the ratio of CD3+ CD8+ CD38+ HLA DR . Samples were obtained for CD3+ CD8+ CD38+ HLA DR as measurements of viral suppression during antiretroviral therapy.
Measured: after 2 weeks of treatment till 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
Tipranavir (TPV) and Ritonavir (RTV) trough concentrations from plasma samples at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
Measured: after 2 weeks of treatment till Week 48
Patients Adherence With Study Medication Based on Pill Count
number of pills actually taken divided by the planned number of pills the patient should take
Measured: After 4 weeks of treatment until the end of the trial
Occurrence of Tipranavir (TPV) Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured
A high inhibitory quotient (IQ), the ratio of trough plasma drug concentration to the protein-adjusted viral IC50, is a useful indicator of the potential efficacy margin of antiretroviral drugs. The IQ for TPV is calculated by the formula IQ = TPV Ctrough / (3.75 x Z x fold change of the patients virus), where Z = wild type control IC50 IIIB.
Measured: After 2 weeks of treatment until the end of trial
Occurrence of Tipranavir (TPV) Trough Concentration >120 μM
Patients with TPV trough above 120 μM are at high risk of developing a Grade 3 or 4 ALT or AST elevations. The risk of Grade 3 or greater transaminase elevations appeared to be uniform at TPV trough concentration below 120 μM. Hence, for this study the TPV trough should be maintained below 120 μM.
Measured: After 2 weeks of treatment until the end of trial
Post-dose Tipranavir (TPV) and Ritonavir (RTV) Concentrations at Week 4
Post-dose Tipranavir (TPV) and Ritonavir (RTV) plasma concentrations at Week 4
Measured: Week 4
Frequency of Patients (%) With Possible Clinically Significant Abnormalities of Laboratory Measurements
Frequency of patients (%) with possible clinically significant abnormalities of laboratory measurements (haematology, differentials (automatic and absolute), coagulation, electrolytes, enzymes, substrates, urinalysis, serology and T-cells)
Measured: Baseline through 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2007 (estimated)
- Study startMar 2007
- Primary completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00447902
- Sponsor's protocol ID
- 1182.99
- Other IDs
- EudraCT No.: 2005-005023-33
- Status last verified
- Apr 2014
- First submitted
- 14 Mar 2007
- Last updated
- 14 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Antiviral Activity of TPV in Hepatitis C or Hepatitis B HIV Coinfected Patients - TDM Randomised Pilot Evaluation
- ClinicalTrials.gov ID
- NCT00447902
- Acronym / sponsor ID
- 1182.99
- Conditions
- HIV Infections
- Keywords
- treatment experienced
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Mar 2007
- Primary completion
- Oct 2008 (actual)
- First posted
- 15 Mar 2007 (estimated)
- Results
- Posted 23 Dec 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tipranavir | Drug | – |
| ritonavir | Drug | – |
Primary outcome
Treatment Response at Week 48
Time frame: 48 weeks
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
The Primary Safety Endpoint Was the Occurrence of Dose-limiting Hepatotoxicity During the Study.
Time frame: From the start of the study through 48 weeks.
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.
16 secondary outcomes
Virologic Response Defined as Viral Load <50 Copies/mL at Each Visit
Time frame: 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
Time frame: 24 and 48 weeks
Occurrence of Viral Load Less Than 400 Copies/mL at Each Visit
Time frame: 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
Time frame: Baseline, 24 and 48 weeks
Change in Viral Load From Baseline at Each Visit
Time frame: After 4 weeks of treatment until the end of the trial
Time to Treatment Failure
Time frame: After Day 1 of treatment until the end of the trial
Time to New AIDS or AIDS Related Progression Event or Death
Time frame: After Day 1 of treatment until the end of the trial
Change in CD4+ and CD8+ Cell Counts From Baseline to Week 48
Time frame: after 2 weeks of treatment till Week 48
Change in Ratio of CD38+/CD8+ From Baseline to Week 48
Time frame: after 2 weeks of treatment till Week 48
Change in Ratio of CD3+ CD8+ CD38+ HLA DR From Baseline to Week 48.
Time frame: after 2 weeks of treatment till 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
Time frame: after 2 weeks of treatment till Week 48
Patients Adherence With Study Medication Based on Pill Count
Time frame: After 4 weeks of treatment until the end of the trial
Occurrence of Tipranavir (TPV) Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured
Time frame: After 2 weeks of treatment until the end of trial
Occurrence of Tipranavir (TPV) Trough Concentration >120 μM
Time frame: After 2 weeks of treatment until the end of trial
Post-dose Tipranavir (TPV) and Ritonavir (RTV) Concentrations at Week 4
Time frame: Week 4
Frequency of Patients (%) With Possible Clinically Significant Abnormalities of Laboratory Measurements
Time frame: Baseline through 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
30 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tipranavir and ritonavir in people with HIV Infections, run by Boehringer Ingelheim at 30 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in France, United States, Italy, Brazil, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Dec 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Response at Week 48 (time frame: 48 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2014.