Clinical Trials

MainTitle

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

This study has been completed
Sponsor
Boehringer Ingelheim


Information provided by (Responsible Party)
Boehringer Ingelheim
ClinicalTrials.gov Identifier
NCT02238314

First received: September 11, 2014
Last updated: September 11, 2014
Last Verified: September 2014
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infections

Drug : Tipranavir low dose
Drug : Tipranavir high dose
Drug : Ritonavir
Drug : Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Drug : Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures

  • Change from baseline in HIV-1 RNA concentrations [ Time Frame: 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
  • Occurrence of HIV-1 RNA levels BLQ (50 copies/mL) [ Time Frame: up to 112 weeks ]
    measured by the Roche Amplicor UltraSensitive™ PCR Method
  • Number of patients with treatment-emergent and drug-related adverse events (AEs) [ Time Frame: up to 115 weeks ]
  • Number of patients with serious adverse events (SAEs) [ Time Frame: up to 115 weeks ]
  • Number of patients with grade 3 and 4 laboratory abnormalities [ Time Frame: up to 115 weeks ]
Secondary Outcome Measures:
  • Change from baseline in cluster of differentiation (CD) 4+ cell count responses [ Time Frame: weeks 24, 48 and 80 ]
  • Change from baseline in CD8+ cell count responses [ Time Frame: weeks 24, 48 and 80 ]
  • Time to new or recurring AIDS-defining illness [ Time Frame: up to 115 weeks ]
  • Time to new or recurring HIV-related illness [ Time Frame: up to 115 weeks ]
  • Time to death [ Time Frame: up to 115 weeks ]
  • Occurrence of AIDS-defining illness, [ Time Frame: up to 115 weeks ]
  • Occurrence of HIV-related illness, [ Time Frame: up to 115 weeks ]
  • Occurrence of death [ Time Frame: 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
  • Change from baseline in cholesterol [ Time Frame: up to 115 weeks ]
  • Change from baseline in HDL [ Time Frame: up to 115 weeks ]
  • Change from baseline in triglycerides [ Time Frame: up to 115 weeks ]
  • Change from baseline in blood glucose [ Time Frame: up to 115 weeks ]
  • Steady-state plasma concentrations [ Time Frame: 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)

Enrollment: 41
Study Start Date: January 1999
Primary Completion Date: August 2001 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Tipranavir low dose

Drug: Tipranavir low dose
Drug: Ritonavir
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Drug: Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
Experimental: Tipranavir high dose

Drug: Tipranavir high dose
Drug: Ritonavir
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Drug: Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
Eligibility

Eligibility

Ages Eligible for Study: 13 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

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

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02238314

Sponsors and Collaborators

Boehringer Ingelheim
More Information

More Information

Additional Information:

Related Info

Responsible Party: Boehringer Ingelheim  
ClinicalTrials.gov Identifier: NCT02238314   History of Changes  
Other Study ID Numbers: 1182.2  
Study First Received: September 11, 2014  
Last Updated: September 11, 2014  

Additional relevant MeSH terms:
HIV Infections
Ritonavir
HIV Protease Inhibitors
Tipranavir
Protease Inhibitors
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this data on December 18, 2017
This information is provided by ClinicalTrials.gov.