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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02238314
• Other study ID #: 1182.2
• Status: Completed
• Phase: Phase 2
• First received: September 11, 2014
• Last updated: September 11, 2014
• Start date: January 1999

Study information

• Verified date: September 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. primary completion date: August 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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 ß-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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Tipranavir low dose

• Tipranavir high dose

• Ritonavir

• Nucleoside Reverse Transcriptase Inhibitor (NRTI)

• Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in HIV-1 RNA concentrations		weeks 16, 24, 48 and 80	No
Primary	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	up to 112 weeks	No
Primary	Occurrence of HIV-1 RNA levels BLQ (50 copies/mL)	measured by the Roche Amplicor UltraSensitive™ PCR Method	up to 112 weeks	No
Primary	Number of patients with treatment-emergent and drug-related adverse events (AEs)		up to 115 weeks	No
Primary	Number of patients with serious adverse events (SAEs)		up to 115 weeks	No
Primary	Number of patients with grade 3 and 4 laboratory abnormalities		up to 115 weeks	No
Secondary	Change from baseline in cluster of differentiation (CD) 4+ cell count responses		weeks 24, 48 and 80	No
Secondary	Change from baseline in CD8+ cell count responses		weeks 24, 48 and 80	No
Secondary	Time to new or recurring AIDS-defining illness		up to 115 weeks	No
Secondary	Time to new or recurring HIV-related illness		up to 115 weeks	No
Secondary	Time to death		up to 115 weeks	No
Secondary	Occurrence of AIDS-defining illness,		up to 115 weeks	No
Secondary	Occurrence of HIV-related illness,		up to 115 weeks	No
Secondary	Occurrence of death		up to 115 weeks	No
Secondary	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	up to 115 weeks	No
Secondary	Change from baseline in cholesterol		up to 115 weeks	No
Secondary	Change from baseline in HDL		up to 115 weeks	No
Secondary	Change from baseline in triglycerides		up to 115 weeks	No
Secondary	Change from baseline in blood glucose		up to 115 weeks	No
Secondary	Steady-state plasma concentrations		up to week 24	No
Secondary	Fold-change in concentration required to produce 50% of inhibition (IC 50)	sequence-based HIV-1 analysis (genotyping) and drugs susceptibility assays (phenotyping)	Baseline, weeks 24, 48 and 80	No

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