Tipranavir and Ritonavir vs. Saquinavir and Ritonavir Used With Two Nucleoside Reverse Transcriptase Inhibitors in Single Protease Inhibitor-experienced HIV-1 Patients

HIV Infections Clinical Trial

Official title:

Tipranavir: An Open-label, Randomized Study Comparing Combination Therapy (Tipranavir and Ritonavir vs. Saquinavir and Ritonavir) Used With Two Nucleoside Reverse Transcriptase Inhibitors in Single Protease Inhibitor-experienced HIV-1 Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02239835
• Other study ID #: 1182.4
• Status: Terminated
• Phase: Phase 2
• First received: September 11, 2014
• Last updated: September 11, 2014
• Start date: December 1999

Study information

• Verified date: September 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFrance: Agence Nationale de Sécurité du Médicament et des produits de santéItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

Objectives of the study were to evaluate the efficacy and safety of two different doses of tipranavir (TPV) in combination with ritonavir (TPV/r) compared with a standard dual PI combination of saquinavir (SQV) and ritonavir (RTV) and to evaluate the dose response of two different doses of TPV in combination with RTV for efficacy and safety.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 79
• Est. primary completion date: November 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Clinical failure while on the current PI-containing regimen of indinavir, nelfinavir, or amprenavir

• In the investigator's opinion, adherence to the present PI-containing regimen

• Exposure of >=6 months to the current PI therapy

• Stable PI-containing regimen, i.e., receiving the current two reverse transcriptase inhibitors (RTIs) for at least 2 months prior to study entry

• HIV-1 RNA >=1000 copies/mL (assayed using the Amplicor polymerase chain reaction (PCR) method at the initial screening visit)

• No limit in CD4+ cell count at the initial screening

• At least two new nucleoside reverse transcriptase inhibitor (NRTI) options available

• Age >=18 years

• Acceptable screening laboratory test values that indicated adequate baseline organ function at the time of screening. Acceptable laboratory test values consisted of the following: severity <=Grade 1 (ACTG Grading Scale). Stable Grade 2 abnormalities were permitted if the values had been demonstrated and documented for at least >=2 months. All laboratory values >Grade 2 were subject to approval by the P&U Clinical Program Leader or designated personnel and subsequently by the BI designated personnel

• Acceptable medical history, physical examination, ECG, and chest radiograph prior to entry into the treatment phase of the study

• Use of a barrier contraceptive method of birth control for at least 30 days prior to study drug administration, during the study, and 30 days after study completion

• Ability to swallow numerous tablets and capsules without difficulty

• Ability to understand and provide informed consent. Minors had to have approval of a parent or legal guardian

Exclusion Criteria:

• Treatment with more than one PI-containing regimen

• Clinically significant active or acute (onset within the month previous to study entry) medical problems, including the following: opportunistic infections, e.g., active cryptococcosis, Pneumocystis carinii pneumonia, herpes zoster, histoplasmosis, or cytomegalovirus; nonopportunistic diseases, including but not limited to the following: progressive multifocal leukoencephalopathy, lymphoma, or malignancy requiring systemic therapy

• Prior exposure (>7 days) to tipranavir, saquinavir, or ritonavir

• 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, saquinavir, or ritonavir

• Use of interferons, interleukins, HIV vaccines, or any active immunizations within 30 days of study entry

• Taking of any investigational medication with the exception of adefovir dipivoxil (Preveon™) 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 substance abuse, which in the investigator's opinion could affect adherence 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 (TPV) low dose

• Tipranavir (TPV) high dose

• Ritonavir low dose

• Ritonavir high dose

• Saquinavir

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 plasma HIV-1 RNA concentrations		Week 16, 24 and 48	No
Primary	Occurrence of HIV-1 RNA levels below the limit of quantitation (BLQ)	using the Roche Amplicor HIV Monitor™ Method [limit of detection (LD) 400 copies/mL] and the Roche Amplicor UltraSensitive Method™ (LD 50 copies/mL)	up to 96 weeks	No
Primary	Number of patients with treatment-emergent and drug-related adverse events (AEs)		up to 96 weeks	No
Primary	Number of patients with serious adverse events (SAEs)		up to 96 weeks	No
Primary	Number of patients with grade 3 and 4 laboratory abnormalities		up to 96 weeks	No
Secondary	Change from baseline in cluster of differentiation (CD) 4+ cell count		Week 16, 24 and 48	No
Secondary	Time to virologic failure	defined as plasma HIV-1 RNA values >400 copies/mL at two consecutive time points 2 to 4 weeks apart	after week 16	No
Secondary	Occurrence of new or recurring AIDS-defining illnesses		up to 96 weeks	No
Secondary	Occurrence of HIV-1 related illness		up to 96 weeks	No
Secondary	Occurrence of death		up to 96 weeks	No
Secondary	Time to new or recurring AIDS-defining illnesses		up to 96 weeks	No
Secondary	Time to HIV-1 related illness		up to 96 weeks	No
Secondary	Time to death		up to 96 weeks	No
Secondary	Change from baseline in blood glucose		up to 96 weeks	No
Secondary	Change from baseline in cholesterol		up to 96 weeks	No
Secondary	Change from baseline in high density lipoprotein (HDL)		up to 96 weeks	No
Secondary	Change from baseline in triglycerides		up to 96 weeks	No
Secondary	Time to virologic response		up to 96 weeks	No
Secondary	Trough plasma tipranavir concentrations		up to week 24	No
Secondary	Sequence-based HIV-1 analysis (genotyping) and drug susceptibility assays (phenotyping)		Baseline and week 24	No

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