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

NCT02238314 | Completed Phase 2

• 1 other identifier: 1182.2
• Study Type: interventional
• Target: 41
• Locations: 0 countries
• Sites: N/A

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (6)

• Change from baseline in HIV-1 RNA concentrations

  weeks 16, 24, 48 and 80

• 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

• Occurrence of HIV-1 RNA levels BLQ (50 copies/mL)

  measured by the Roche Amplicor UltraSensitive™ PCR Method

  up to 112 weeks

• Number of patients with treatment-emergent and drug-related adverse events (AEs)

  up to 115 weeks

• Number of patients with serious adverse events (SAEs)

  up to 115 weeks

• Number of patients with grade 3 and 4 laboratory abnormalities

  up to 115 weeks

Secondary Outcomes (15)

• Change from baseline in cluster of differentiation (CD) 4+ cell count responses

  weeks 24, 48 and 80

• Change from baseline in CD8+ cell count responses

  weeks 24, 48 and 80

• Time to new or recurring AIDS-defining illness

  up to 115 weeks

• Time to new or recurring HIV-related illness

  up to 115 weeks

• Time to death

  up to 115 weeks

Study Arms (2)

Tipranavir low dose

EXPERIMENTAL

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

Tipranavir high dose

EXPERIMENTAL

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

Interventions

Tipranavir low dose DRUG

Tipranavir low dose

Tipranavir high dose DRUG

Tipranavir high dose

Ritonavir DRUG

Tipranavir high dose; Tipranavir low dose

Nucleoside Reverse Transcriptase Inhibitor (NRTI) DRUG

Tipranavir high dose; Tipranavir low dose

Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) DRUG

Tipranavir high dose; Tipranavir low dose

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

HIV Infections

Interventions

tipranavir; Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2014
• First Posted: September 12, 2014
• Study Start: January 1, 1999
• Primary Completion: August 1, 2001
• Last Updated: September 12, 2014

Record last verified: 2014-09