Tipranavir/Ritonavir vs. Genotypically Defined Protease Inhibitor/Ritonavir in HIV Patients (RESIST-2)

Boehringer Ingelheim882 enrolled

Overview

The objective of this study is to demonstrate the safety and efficacy of tipranavir/ritonavir versus an active control arm in highly treatment experienced Human immunodeficiency virus-1 infected patients. Patients must have a viral load \> =1000 cells/mL, and genotype indicating at least one resistance conferring protease inhibitor-mutation as determined from a predefined panel of mutations. Any CD4+ count is acceptable.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Enrollment

882

Conditions

HIV Infections

Interventions

Tipranavir (with low dose ritonavir)DRUG

Comparator protease inhibitor(CPI)/low dose ritonavir(r)DRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed informed consent prior to trial participation. 2. Human immunodeficiency virus-1 infected males or females \>=18 years of age. 3. Screening genotypic resistance report indicating both of the following: * at least one primary protease mutation at the following sites 30N, 46I/L, 48V, 50V, 82A/F/L/T, 84V or 90M , and * no more than two protease mutations on codons 33, 82, 84, or 90. 4. At least 3 consecutive months experience taking antiretrovirals from each of the classes of Nucleoside reverse transcriptase inhibitor(s), Non-nucleoside reverse transcriptase inhibitor(s), and Protease inhibitor(s) at some point in treatment history, * with at least 2 Protease inhibitor-based regimens (minimum 3 months of exposure of each), one of which must be part of the current regimen, and * current Protease inhibitor-based antiretroviral medication regimen for at least 3 months prior to randomisation. 5. Human immunodeficiency virus-1 viral load \>=1000 copies/mL at screening. 6. Acceptable screening laboratory values that indicate adequate baseline organ function. Laboratory values are considered to be acceptable if the following apply: * Total cholesterol \<=400 mg/dl or 10,36 mm/L. * Total triglycerides \<=750 mg/dl or 8,5 mm/L. * Alanine aminotransferase \<=3x upper limit of normal and aspartate aminotransferase \<=2.5x upper limit of normal. * Any Grade gamma-glutamyl transpeptidase is acceptable. * Any Grade creatinine kinase is acceptable as long as there is no concurrent myopathy. * All other laboratory test values \<= Grade 1(Division of Acquired immune deficiency syndrome, National Institute of Health grading scale). 7. Acceptable medical history, as assessed by the investigator, with chest X-ray and electrocardiogram within 1 year of study participation. 8. Willingness to abstain from ingesting substances during the study which may alter plasma study drug levels by interaction with the cytochrome P450 system. 9. A prior Acquired immune deficiency syndrome-defining event is acceptable as long as it has resolved or the patient has been on stable treatment for at least 2 months (Acquired immune deficiency syndrome related complex is acceptable). Exclusion Criteria: 1. Antiretroviral medication naïve. 2. Patients on recent drug holiday, defined as off antiretroviral medications for at least 7 consecutive days within the last 3 months. 3. Alanine aminotransferase \>3x upper limit of normal and aspartate aminotransferase \>2.5x upper limit of normal at either screening visit. 4. Female patients of child-bearing potential who: * have a positive serum pregnancy test at screening or during the study, * are breast feeding * are planning to become pregnant, or * are not willing to use a barrier method of contraception, or * require ethinyl estradiol administration 5. Prior tipranavir use. 6. Use of investigational medications within 30 days before study entry or during the trial. (T-20 \[enfuvirtide\] and Tenofovir (Viread), investigational at the time of writing of this protocol, will be allowed.) 7. Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g. interferon, cyclosporin, hydroxyurea, interleukin 2). 8. Inability to adhere to the requirements of the protocol, including active substance abuse as assessed by the investigator. 9. In the opinion of the investigator, likely survival of less than 12 months because of underlying disease.

Locations (174)

Outcomes

Primary Outcomes

Treatment Response at Week 48

Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound

Time frame: after 48 weeks of treatment

Time to Treatment Failure Through 48 Weeks of Treatment

Time to treatment failure is defined as 0 for patients who never achieve TR otherwise time to treatment failure is the earliest time of death, discontinuation of the study drug or introduction of a new anti-retroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background, or the first of two consecutive visits with Log(baseline Viral Load) - Log(on-treatment Viral Load) \< 1.

Time frame: after 48 weeks of treatment

Secondary Outcomes

Treatment Response at Week 2

Time frame: week 2

Treatment Response at Week 4

Time frame: week 4

Treatment Response at Week 8

Time frame: week 8

Treatment Response at Week 16

Data from ClinicalTrials.gov

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1182.48.5401 Fundación Huésped

Buenos Aires, Argentina

1182.48.5402 Fundación Huésped

Buenos Aires, Argentina

1182.48.5403 Servicio de Infecciosas

Buenos Aires, Argentina

1182.48.5404 Servicio de Infecciosas

Buenos Aires, Argentina

1182.48.5405 Hospital Muniz

Buenos Aires, Argentina

1182.48.5406 Servicio de Immunocomprometido

Buenos Aires, Argentina

1182.48.4301 Boehringer Ingelheim Investigational Site

Vienna, Austria

1182.48.3209 Boehringer Ingelheim Investigational Site

Antwerp, Belgium

1182.48.3201 Boehringer Ingelheim Investigational Site

Brussels, Belgium

1182.48.3202 Boehringer Ingelheim Investigational Site

Brussels, Belgium

...and 164 more locations

Treatment Response at Week 24

Time frame: Week 24

Treatment Response at Week 32

Time frame: week 32

Treatment Response at Week 40

Time frame: week 40

Treatment Response at Week 56

Time frame: week 56

Treatment Response at Week 64

Time frame: week 64

Treatment Response at Week 72

Time frame: week 72

Treatment Response at Week 80

Time frame: week 80

Treatment Response at Week 88

Time frame: week 88

Treatment Response at Week 96

Time frame: after 96 weeks of treatment

Time to Treatment Failure Through 96 Weeks of Treatment

Time frame: after 96 weeks of treatment

Time to Confirmed Virologic Failure Through 48 Weeks of Treatment

Time to virologic failure is defined as the time from the start of treatment to the last measurement where the Log(baseline viral load)-Log(on-treatment viral load)\>1 before a 2 consecutive measurements where Log(baseline viral load)-Log(on-treatment viral load)\<1.

Time frame: after 48 weeks of treatment

Time to Confirmed Virologic Failure Through 96 Weeks of Treatment

Time frame: after 96 weeks of treatment

Virologic Response

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: Week 2 through Week 96 (at any point during trial)

Virologic Response at Week 2

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: Week 2

Virologic Response at Week 4

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: week 4

Virologic Response at Week 8

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: week 8

Virologic Response at Week 16

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: week 16

Virologic Response at Week 24

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: week 24

Virologic Response at Week 32

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: week 32

Virologic Response at Week 40

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: week 40

Virologic Response at Week 48

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: week 48

Virologic Response at Week 56

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: week 56

Virologic Response at Week 64

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: week 64

Virologic Response at Week 72

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: Week 72

Virologic Response at Week 80

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: Week 80

Virologic Response at Week 88

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: Week 88

Virologic Response at Week 96

Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)\>=1

Time frame: Week 96

Median Change From Baseline in Viral Load (Week 2)

Time frame: Baseline to Week 2

Median Change From Baseline in Viral Load (Week 4)

Time frame: Baseline to Week 4

Median Change From Baseline in Viral Load (Week 8)

Time frame: Baseline to Week 8

Median Change From Baseline in Viral Load (Week 16)

Time frame: Baseline to Week 16

Median Change From Baseline in Viral Load (Week 24)

Time frame: Baseline to Week 24

Median Change From Baseline in Viral Load (Week 32)

Time frame: Baseline to Week 32

Median Change From Baseline in Viral Load (Week 40)

Time frame: Baseline to Week 40

Median Change From Baseline in Viral Load (Week 48)

Time frame: Baseline to Week 48

Median Change From Baseline in Viral Load (Week 56)

Time frame: Baseline to Week 56

Median Change From Baseline in Viral Load (Week 64)

Time frame: Baseline to Week 64

Median Change From Baseline in Viral Load (Week 72)

Time frame: Baseline to Week 72

Median Change From Baseline in Viral Load (Week 80)

Time frame: Baseline to Week 80

Median Change From Baseline in Viral Load (Week 88)

Time frame: Baseline to Week 88

Median Change From Baseline in Viral Load (Week 96)

Time frame: Baseline to Week 96

Virologic Response at Week 40