Exploratory Study of Tipranavir and Ritonavir in Multiple Protease Inhibitor-experienced HIV Patients
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Tipranavir low dose
Tipranavir high dose
Ritonavir
Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Tipranavir low dose
Tipranavir high dose
Arm Description
Outcomes
Primary Outcome Measures
Change from baseline in HIV-1 RNA concentrations
Occurrence of HIV-1 RNA levels below the limit of quantitation (BLQ) (400 copies/mL)
measured by the Roche Amplicor HIV-1 Monitor™ polymerase chain reaction (PCR) Method
Occurrence of HIV-1 RNA levels BLQ (50 copies/mL)
measured by the Roche Amplicor UltraSensitive™ PCR Method
Number of patients with treatment-emergent and drug-related adverse events (AEs)
Number of patients with serious adverse events (SAEs)
Number of patients with grade 3 and 4 laboratory abnormalities
Secondary Outcome Measures
Change from baseline in cluster of differentiation (CD) 4+ cell count responses
Change from baseline in CD8+ cell count responses
Time to new or recurring AIDS-defining illness
Time to new or recurring HIV-related illness
Time to death
Occurrence of AIDS-defining illness,
Occurrence of HIV-related illness,
Occurrence of death
Time to virologic failure
defined as plasma HIV-1 RNA values >400 copies/mL or a 0.5 log reduction from baseline at two consecutive time points
Change from baseline in cholesterol
Change from baseline in HDL
Change from baseline in triglycerides
Change from baseline in blood glucose
Steady-state plasma concentrations
Fold-change in concentration required to produce 50% of inhibition (IC 50)
sequence-based HIV-1 analysis (genotyping) and drugs susceptibility assays (phenotyping)
Full Information
NCT ID
NCT02238314
First Posted
September 11, 2014
Last Updated
September 11, 2014
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT02238314
Brief Title
Exploratory Study of Tipranavir and Ritonavir in Multiple Protease Inhibitor-experienced HIV Patients
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
January 1999 (undefined)
Primary Completion Date
August 2001 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tipranavir low dose
Arm Type
Experimental
Arm Title
Tipranavir high dose
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Tipranavir low dose
Intervention Type
Drug
Intervention Name(s)
Tipranavir high dose
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Type
Drug
Intervention Name(s)
Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Intervention Type
Drug
Intervention Name(s)
Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
Primary Outcome Measure Information:
Title
Change from baseline in HIV-1 RNA concentrations
Time Frame
weeks 16, 24, 48 and 80
Title
Occurrence of HIV-1 RNA levels below the limit of quantitation (BLQ) (400 copies/mL)
Description
measured by the Roche Amplicor HIV-1 Monitor™ polymerase chain reaction (PCR) Method
Time Frame
up to 112 weeks
Title
Occurrence of HIV-1 RNA levels BLQ (50 copies/mL)
Description
measured by the Roche Amplicor UltraSensitive™ PCR Method
Time Frame
up to 112 weeks
Title
Number of patients with treatment-emergent and drug-related adverse events (AEs)
Time Frame
up to 115 weeks
Title
Number of patients with serious adverse events (SAEs)
Time Frame
up to 115 weeks
Title
Number of patients with grade 3 and 4 laboratory abnormalities
Time Frame
up to 115 weeks
Secondary Outcome Measure Information:
Title
Change from baseline in cluster of differentiation (CD) 4+ cell count responses
Time Frame
weeks 24, 48 and 80
Title
Change from baseline in CD8+ cell count responses
Time Frame
weeks 24, 48 and 80
Title
Time to new or recurring AIDS-defining illness
Time Frame
up to 115 weeks
Title
Time to new or recurring HIV-related illness
Time Frame
up to 115 weeks
Title
Time to death
Time Frame
up to 115 weeks
Title
Occurrence of AIDS-defining illness,
Time Frame
up to 115 weeks
Title
Occurrence of HIV-related illness,
Time Frame
up to 115 weeks
Title
Occurrence of death
Time Frame
up to 115 weeks
Title
Time to virologic failure
Description
defined as plasma HIV-1 RNA values >400 copies/mL or a 0.5 log reduction from baseline at two consecutive time points
Time Frame
up to 115 weeks
Title
Change from baseline in cholesterol
Time Frame
up to 115 weeks
Title
Change from baseline in HDL
Time Frame
up to 115 weeks
Title
Change from baseline in triglycerides
Time Frame
up to 115 weeks
Title
Change from baseline in blood glucose
Time Frame
up to 115 weeks
Title
Steady-state plasma concentrations
Time Frame
up to week 24
Title
Fold-change in concentration required to produce 50% of inhibition (IC 50)
Description
sequence-based HIV-1 analysis (genotyping) and drugs susceptibility assays (phenotyping)
Time Frame
Baseline, weeks 24, 48 and 80
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
Learn more about this trial
Exploratory Study of Tipranavir and Ritonavir in Multiple Protease Inhibitor-experienced HIV Patients
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