Comparison of TPV/r to DRV/r in Triple Class Experienced Patient With Resistance to > 1 PI

Phase 3

Terminated

• Conditions: HIV Infections

• Registration Number: NCT00517192
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The objective of this study is to compare the efficacy and safety of Tipranavir/ritonavir (TPV/r, 500mg/200mg twice daily) to the safety and efficacy of Darunavir/ritonavir (DRV/r 600 mg /100 mg twice daily) in combination with investigator selected optimised background regimens in patients who are three-class (Nucleoside reverse transcriptase inhibitors (NRTI), Nonnucleoside reverse transcriptase inhibitors (NNRTI), and Protease inhibitor (PI)) treatment-experienced (a minimum of 3-months duration for each class) with resistance to more than one PI on the screening virtual phenotype resistance testing.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-08-15
• Study First Submitted QC: 2007-08-15
• Study First Posted: 2007-08-16
• Study Start: 2007-09
• Primary Completion: 2008-09
• Results First Submitted: 2009-09-18
• Results First Submitted QC: 2009-09-18
• Results First Posted: 2009-10-23
• Status Verified: 2014-04
• Last Update Submitted: 2014-04-25
• Last Update Posted: 2014-05-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Signed informed consent prior to trial participation.

2. HIV-1 infected male or female >18 years of age.

3. Three-class (NRTI, NNRTI, and PI) treatment-experienced patients (a minimum of 3-months duration for each class or documented class hypersensitivity/intolerance) with resistance (minimal or reduced response) to more than one PI on the screening virtual phenotype resistance testing. In the case of NNRTIs, NNRTI resistance in the absence of exposure is equivalent to being NNRTI treatment experienced.

4. Patient's optimized background regimen must contain one of the following ARV options:

   • A minimum of two genotypically active nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) reported as "maximal response" or "sensitive" on the screening virtual phenotype report.
   • A minimum of one genotypically active NRTI reported as "maximal response" or "sensitive" on the screening virtual phenotype report plus Enfuvirtide if not used previously.
   • A minimum of one genotypically active NRTI reported as "maximal response" or "sensitive" on the screening virtual phenotype report plus an integrase inhibitor if not used previously and if available through an expanded access program and allowed by local regulatory authorities.
   • A minimum of one genotypically active NRTI reported as "maximal response" or "sensitive" on the screening virtual phenotype report plus the CCR5 chemokine receptor antagonist Maraviroc if available through an expanded access program, not used previously and allowed by local regulatory authorities.
   • Zero or one genotypically active NRTI reported as "maximal response" or "sensitive" on the screening virtual phenotype report plus two of the following drugs, Enfuvirtide, an integrase inhibitor and Maraviroc if available, not used previously and allowed by local regulatory authorities.
   • Two genotypically partially active NRTIs (provided that they are not part of the current failing regimen) reported as "reduced response" on the screening virtual phenotype report plus one of the following drugs, Enfuvirtide, an integrase inhibitor or Maraviroc if available, not used previously and allowed by local regulatory authorities.

5. Patient has been on their current (failing) PI-containing regimen for at least 8 weeks prior to randomization.

6. Patient has on-going viral replication (defined as an HIV-1 viral load of ≥ 500 copies/mL) and a successful virtual phenotype obtained at screening.

7. Any baseline CD4 cell count will be allowed.

8. Karnofsky performance score of ≥ 70.

9. Acceptable screening laboratory values that indicate adequate baseline organ function. Laboratory values are considered acceptable if the following apply:

   • ALT ≤2.5 x ULN and AST ≤2.5 x ULN (≤DAIDS Grade 1, Appendix 10.1).
   • Any DAIDS grade cholesterol, triglycerides, GGT, CPK or LDH is acceptable.
   • All other laboratory test values must be ≤DAIDS Grade 2.

10. Willingness to initiate CD4+ cell count-guided chemoprophylaxis to prevent opportunistic infections.

11. Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system during the study.

Inclusion Criteria:

1. Previous use of Tipranavir (TPV) or Darunavir (DRV).

2. Full genotypic resistance (reported as minimal response) to Tipranavir (TPV) or Darunavir (DRV) on screening virtual phenotype:

3. Female patient of child-bearing potential who:

   has a positive serum pregnancy test at screening, is breast feeding, is planning to become pregnant, is not willing to use double-barrier methods (simultaneous use of two different methods such as diaphragm with spermicidal substance and condom) of contraception or requires ethinyl estradiol administration. Barrier methods of contraception include diaphragm with spermicidal substance, condom for females, cervical caps and condoms.

4. History of Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any malignancy.

5. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit.

6. Use of immunomodulatory drugs (such as interferon, cyclosporin, hydroxyurea and interleukin 2) within 30 days prior to randomization.

7. Current use of systemic cytotoxic chemotherapy.

8. All contraindications listed in the product monographs of Aptivus, Prezista and Norvir.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Time to Virologic Failure Through 48 Weeks of Treatment, Using Viral Load (VL) < 50 Copies/Millilitre (mL) as the Response Criterion.	48 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Treatment Response at Week 48, Using VL < 50 Copies/mL as the Response Criterion and the FDA Definition for Handling Drug Discontinuations ((NCF) Non-Completers=Failure).	48 weeks of treatment
Intent-To-Treat Analysis of Virologic Response at Week 48, Using VL < 50 Copies/mL as the Response Criterion Where Patients Are Followed Until Week 48 for VL Regardless of Whether or Not They Remain on Study Drug.	48 weeks of treatment
Time to Virologic Failure Through 48 Weeks of Treatment, Using VL < 400 Copies/mL as the Response Criterion.	48 weeks of treatment
Response up to 48 Weeks Using VL < 50 Copies/mL Using Censored	up to 48 weeks
Response up to 48 Weeks Using VL < 50 Copies/mL Using NCF	up to 48 weeks
Response up to 48 Weeks Using VL < 50 Copies/mL Using Intent-to-treat	up to 48 weeks
Response up to 48 Weeks Using VL < 400 Copies/mL Using Censored	up to 48 weeks
Response up to 48 Weeks Using VL < 400 Copies/mL Using NCF	up to 48 weeks
Response up to 48 Weeks Using VL < 400 Copies/mL Using Intent-to-treat	up to 48 weeks
Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using Censored	up to 48 weeks
Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using NCF	up to 48 weeks
Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using Intent-to-treat	up to 48 weeks
Daily Average in CD4+ Cell Count Change From Baseline at up to Week 8	up to week 8
Daily Average in CD4+ Cell Count Change From Baseline up to Week 24	up to week 24
Daily Average in CD4+ Cell Count Change From Baseline up to Week 48	up to week 48
Daily Average in Viral Load Change From Baseline up to Week 8	up to week 8
Daily Average in Viral Load Change From Baseline up to Week 24	up to week 24
Daily Average in Viral Load Change From Baseline up to Week 48	up to week 48
Change From Baseline in CD4+ Cell Count up to Week 48	up to week 48
Change From Baseline in log10 Viral Load up to Week 48	up to week 48
Occurrence of New AIDS Progression Events or Death	through 48 weeks of treatment

Trial Locations

Locations (54)

1182.71.1002 Boehringer Ingelheim Investigational Site; 🇨🇦 Vancouver, British Columbia, Canada

1182.71.1016 Boehringer Ingelheim Investigational Site; 🇧🇸 Nassau, Bahamas

1182.71.3502 Boehringer Ingelheim Investigational Site; 🇵🇹 Amadora, Portugal

1182.71.6606 Boehringer Ingelheim Investigational Site; 🇹🇭 Nonthaburi, Thailand

1182.71.6604 Boehringer Ingelheim Investigational Site; 🇹🇭 Bangkok, Thailand

1182.71.6603 Boehringer Ingelheim Investigational Site; 🇹🇭 Phathumwan, Thailand

1182.71.3002 Boehringer Ingelheim Investigational Site; 🇬🇷 Athens, Greece

1182.71.3001 Boehringer Ingelheim Investigational Site; 🇬🇷 Piraeus, Greece

1182.71.3504 Boehringer Ingelheim Investigational Site; 🇵🇹 Lisbon, Portugal

1182.71.3503 Boehringer Ingelheim Investigational Site; 🇵🇹 Porto, Portugal

1182.71.6601 Boehringer Ingelheim Investigational Site; 🇹🇭 Bangkok Noi, Thailand

1182.71.6605 Boehringer Ingelheim Investigational Site; 🇹🇭 Chiang Mai, Thailand

1182.71.3306A Boehringer Ingelheim Investigational Site; 🇫🇷 Paris, France

1182.71.3308A Boehringer Ingelheim Investigational Site; 🇫🇷 Paris, France

1182.71.1115 Boehringer Ingelheim Investigational Site; 🇺🇸 Miami, Florida, United States

1182.71.1003 Boehringer Ingelheim Investigational Site; 🇨🇦 Montreal, Quebec, Canada

1182.71.3203 Boehringer Ingelheim Investigational Site; 🇧🇪 Bruxelles, Belgium

1182.71.3205 Boehringer Ingelheim Investigational Site; 🇧🇪 Bruxelles, Belgium

1182.71.1006 Boehringer Ingelheim Investigational Site; 🇨🇦 Montreal, Quebec, Canada

1182.71.1108 Boehringer Ingelheim Investigational Site; 🇺🇸 Tampa, Florida, United States

1182.71.1124 Boehringer Ingelheim Investigational Site; 🇺🇸 Portland, Oregon, United States

1182.71.1001 Boehringer Ingelheim Investigational Site; 🇨🇦 Ottawa, Ontario, Canada

1182.71.1101 Boehringer Ingelheim Investigational Site; 🇺🇸 Ft. Lauderdale, Florida, United States

1182.71.1104 Boehringer Ingelheim Investigational Site; 🇺🇸 Miami, Florida, United States

1182.71.1109 Boehringer Ingelheim Investigational Site; 🇺🇸 Beverly Hills, California, United States

1182.71.1126 Boehringer Ingelheim Investigational Site; 🇺🇸 Charlotte, North Carolina, United States

1182.71.3202 Boehringer Ingelheim Investigational Site; 🇧🇪 Bruxelles, Belgium

1182.71.3206 Boehringer Ingelheim Investigational Site; 🇧🇪 Charleroi, Belgium

1182.71.3312A Boehringer Ingelheim Investigational Site; 🇫🇷 Lyon cedex 3, France

1182.71.1010 Boehringer Ingelheim Investigational Site; 🇨🇦 Montreal, Quebec, Canada

1182.71.3305A Boehringer Ingelheim Investigational Site; 🇫🇷 Bondy, France

1182.71.4907 Boehringer Ingelheim Investigational Site; 🇩🇪 Frankfurt, Germany

1182.71.3303A Boehringer Ingelheim Investigational Site; 🇫🇷 Garches, France

1182.71.3907 Boehringer Ingelheim Investigational Site; 🇮🇹 Pavia, Italy

1182.71.3401 Boehringer Ingelheim Investigational Site; 🇪🇸 Barcelona, Spain

1182.71.4902 Boehringer Ingelheim Investigational Site; 🇩🇪 Berlin, Germany

1182.71.3402 Boehringer Ingelheim Investigational Site; 🇪🇸 Barcelona, Spain

1182.71.1129 Boehringer Ingelheim Investigational Site; 🇵🇷 Ponce, Puerto Rico

1182.71.3405 Boehringer Ingelheim Investigational Site; 🇪🇸 Madrid, Spain

1182.71.3901 Boehringer Ingelheim Investigational Site; 🇮🇹 Brescia, Italy

1182.71.3916 Boehringer Ingelheim Investigational Site; 🇮🇹 Palermo, Italy

1182.71.3310A Boehringer Ingelheim Investigational Site; 🇫🇷 Tourcoing cedex, France

1182.71.4903 Boehringer Ingelheim Investigational Site; 🇩🇪 Mainz, Germany

1182.71.3003 Boehringer Ingelheim Investigational Site; 🇬🇷 Athens, Greece

1182.71.3912 Boehringer Ingelheim Investigational Site; 🇮🇹 Antella (fi), Italy

1182.71.3908 Boehringer Ingelheim Investigational Site; 🇮🇹 Firenze, Italy

1182.71.3919 Boehringer Ingelheim Investigational Site; 🇮🇹 Pescara, Italy

1182.71.3403 Boehringer Ingelheim Investigational Site; 🇪🇸 L'Hospitalet de Llobregat, Spain

1182.71.3407 Boehringer Ingelheim Investigational Site; 🇪🇸 Madrid, Spain

1182.71.6602 Boehringer Ingelheim Investigational Site; 🇹🇭 Khon Kaen, Thailand

1182.71.1118 Boehringer Ingelheim Investigational Site; 🇺🇸 Longview, Texas, United States

1182.71.3301A Boehringer Ingelheim Investigational Site; 🇫🇷 Lyon cedex, France

1182.71.1116 Boehringer Ingelheim Investigational Site; 🇺🇸 Houston, Texas, United States

1182.71.3408 Boehringer Ingelheim Investigational Site; 🇪🇸 Santiago de Compostela, Spain