Clinical trial NCT02238314: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-09-12
Enrollment: 41
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change from baseline in HIV-1 RNA concentrations
timeFrame: weeks 16, 24, 48 and 80
measure: Occurrence of HIV-1 RNA levels below the limit of quantitation (BLQ) (400 copies/mL)
timeFrame: up to 112 weeks
measure: Occurrence of HIV-1 RNA levels BLQ (50 copies/mL)
timeFrame: up to 112 weeks
measure: Number of patients with treatment-emergent and drug-related adverse events (AEs)
timeFrame: up to 115 weeks
measure: Number of patients with serious adverse events (SAEs)
timeFrame: up to 115 weeks
measure: Number of patients with grade 3 and 4 laboratory abnormalities
timeFrame: up to 115 weeks
Secondary outcomes:
measure: Change from baseline in cluster of differentiation (CD) 4+ cell count responses
timeFrame: weeks 24, 48 and 80
measure: Change from baseline in CD8+ cell count responses
timeFrame: weeks 24, 48 and 80
measure: Time to new or recurring AIDS-defining illness
timeFrame: up to 115 weeks
measure: Time to new or recurring HIV-related illness
timeFrame: up to 115 weeks
measure: Time to death
timeFrame: up to 115 weeks
measure: Occurrence of AIDS-defining illness,
timeFrame: up to 115 weeks
measure: Occurrence of HIV-related illness,
timeFrame: up to 115 weeks
measure: Occurrence of death
timeFrame: up to 115 weeks
measure: Time to virologic failure
timeFrame: up to 115 weeks
measure: Change from baseline in cholesterol
timeFrame: up to 115 weeks
measure: Change from baseline in HDL
timeFrame: up to 115 weeks
measure: Change from baseline in triglycerides
timeFrame: up to 115 weeks
measure: Change from baseline in blood glucose
timeFrame: up to 115 weeks
measure: Steady-state plasma concentrations
timeFrame: up to week 24
measure: Fold-change in concentration required to produce 50% of inhibition (IC 50)
timeFrame: Baseline, weeks 24, 48 and 80
Other outcomes:
Locations:
Study officials:
References: