Exploratory Study of Tipranavir and Ritonavir in Multiple Protease Inhibitor-experienced HIV Patients

September 11, 2014 updated by: Boehringer Ingelheim

Tipranavir Disodium: An Open-Label ExploratorySstudy of Tipranavir and Ritonavir in Combination With One Nucleoside Reverse Transcriptase Inhibitor and One Non-Nucleoside Reverse Transcriptase Inhibitor in Multiple Protease Inhibitor-Experienced HIV Patients

The primary objective was to evaluate the antiviral activity and safety of two regimens of tipranavir (500 mg BID or 1000 mg BID) plus ritonavir (100 mg BID) administered in combination with 1 new nucleoside reverse transcriptase inhibitor (NRTI) + efavirenz in multiple protease-inhibitor-experienced HIV-1 positive patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
41

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Multiple (two or more) PI-experience. Eligible patients must have had exposure to at least two antiretroviral regimens containing a single protease inhibitor or a regimen containing dual protease inhibitors
  • In the investigator's opinion, the patient had adhered to PI-containing regimens
  • Exposure of ≥ 3 months to the current PI therapy
  • Exposure of ≥ 4 months to the prior PI therapy with single PI-containing regimens
  • Stable PI-containing regimen for at least 2 months prior to study entry
  • HIV-1-RNA ≥ 5,000 copies/mL
  • Cluster of differentiation (CD)4+ cell count ≥ 50 cells/mm**3
  • At least one new NRTI option available
  • Age ≥ 13 years
  • Acceptable screening laboratory values that indicated adequate baseline organ function at the time of screening. Laboratory values were considered acceptable if the severity was ≤ Grade 1 (AIDS Clinical Trial Group (ACTG) Grading Scale). Stable Grade 2 abnormalities were permitted if the values had been demonstrated and documented for at least ≥ 2 months.
  • Acceptable medical history, physical examination, electrocardiogram, and chest X-ray prior to entry into the treatment phase of the study
  • Agreement to use a barrier contraceptive method of birth control for at least 30 days prior to study drug administration, during the study, and 30 days after the end of the study
  • Ability to swallow numerous tablets and capsules without difficulty
  • Ability to understand and provide informed consent. Minors were required to have approval of a parent or legal guardian

Exclusion Criteria:

  • Prior exposure, defined as > 7 treatment days, to nonnucleoside reverse transcriptase inhibitor (NNRTIs) including, but not limited to: nevirapine, efavirenz, delavirdine, atevirdine, MKC-442, loviride, and HBY-097
  • Clinically significant active or acute (onset within the month previous to study entry) medical problems, including the following: opportunistic infections, such as active cryptococcosis, Pneumocystis carinii pneumonia, herpes zoster, histoplasmosis, or cytomegalovirus or nonopportunistic diseases, including, but not limited to, progressive multifocal leukoencephalopathy, lymphoma, or malignancy requiring systemic therapy
  • Prior exposure (> 7 days) to tipranavir
  • History of clinically significant nervous system or muscle diseases, seizure disorder, or psychiatric disorder that might impair adherence to the protocol
  • Taking of any known P450 3A enzyme-inducing drugs within 30 days of study entry and including the following: rifabutin, rifampin, carbamazepine, dexamethasone, phenobarbital, phenytoin, sulfadimidine, sulfinpyrazone, or troleandomycin
  • Hypersensitivity to tipranavir and/or ritonavir
  • Use of interferons, interleukins, HIV vaccines, or any active immunizations within 30 days prior to study entry
  • Taking of any investigational medication with the exception of adefovir dipivoxil (Preveon™) and amprenavir (Agenerase™) within 30 days of study entry
  • Pregnancy or lactation (serum β-human chorionic gonadotrophin test had to have been negative within 14 days of study entry)
  • Evidence of active substance abuse, which in the investigator's opinion, could affect compliance to the protocol
  • In the investigator's judgment, inability to comply with the protocol requirements for reasons other than those specified

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tipranavir low dose
Drug: Ritonavir
Drug: Tipranavir low dose
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Drug: Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
Experimental: Tipranavir high dose
Drug: Ritonavir
Drug: Tipranavir high dose
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Drug: Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from baseline in HIV-1 RNA concentrations
Time Frame: weeks 16, 24, 48 and 80
weeks 16, 24, 48 and 80
Occurrence of HIV-1 RNA levels below the limit of quantitation (BLQ) (400 copies/mL)
Time Frame: up to 112 weeks
measured by the Roche Amplicor HIV-1 Monitor™ polymerase chain reaction (PCR) Method
up to 112 weeks
Occurrence of HIV-1 RNA levels BLQ (50 copies/mL)
Time Frame: up to 112 weeks
measured by the Roche Amplicor UltraSensitive™ PCR Method
up to 112 weeks
Number of patients with treatment-emergent and drug-related adverse events (AEs)
Time Frame: up to 115 weeks
up to 115 weeks
Number of patients with serious adverse events (SAEs)
Time Frame: up to 115 weeks
up to 115 weeks
Number of patients with grade 3 and 4 laboratory abnormalities
Time Frame: up to 115 weeks
up to 115 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline in cluster of differentiation (CD) 4+ cell count responses
Time Frame: weeks 24, 48 and 80
weeks 24, 48 and 80
Change from baseline in CD8+ cell count responses
Time Frame: weeks 24, 48 and 80
weeks 24, 48 and 80
Time to new or recurring AIDS-defining illness
Time Frame: up to 115 weeks
up to 115 weeks
Time to new or recurring HIV-related illness
Time Frame: up to 115 weeks
up to 115 weeks
Time to death
Time Frame: up to 115 weeks
up to 115 weeks
Occurrence of AIDS-defining illness,
Time Frame: up to 115 weeks
up to 115 weeks
Occurrence of HIV-related illness,
Time Frame: up to 115 weeks
up to 115 weeks
Occurrence of death
Time Frame: up to 115 weeks
up to 115 weeks
Time to virologic failure
Time Frame: up to 115 weeks
defined as plasma HIV-1 RNA values >400 copies/mL or a 0.5 log reduction from baseline at two consecutive time points
up to 115 weeks
Change from baseline in cholesterol
Time Frame: up to 115 weeks
up to 115 weeks
Change from baseline in HDL
Time Frame: up to 115 weeks
up to 115 weeks
Change from baseline in triglycerides
Time Frame: up to 115 weeks
up to 115 weeks
Change from baseline in blood glucose
Time Frame: up to 115 weeks
up to 115 weeks
Steady-state plasma concentrations
Time Frame: up to week 24
up to week 24
Fold-change in concentration required to produce 50% of inhibition (IC 50)
Time Frame: Baseline, weeks 24, 48 and 80
sequence-based HIV-1 analysis (genotyping) and drugs susceptibility assays (phenotyping)
Baseline, weeks 24, 48 and 80

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 1999

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2001

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 11, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 12, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 12, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1182.2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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