Clinical trial NCT00517192: Comparison of TPV/r to DRV/r in Triple Class Experienced Patient With Resistance to > 1 PI
Official title: A Prospective, Randomized, Open-labelled, Multi-centre Trial Comparing the Safety and Efficacy of Ritonavir-boosted Aptivus (Tipranavir, TPV/r) to That of Prezista® (Darunavir, DRV/r) in Three-class (NRTI, NNRTI, and PI) Treatment-experienced Patients With Resistance to More Than One PI. POTENT: PrOspecTive EvaluatioN of Tipranavir vs. Darunavir in Treatment Experienced Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-08-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time to Virologic Failure Through 48 Weeks of Treatment, Using Viral Load (VL) < 50 Copies/Millilitre (mL) as the Response Criterion.
timeFrame: 48 weeks of treatment
Secondary outcomes:
measure: 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).
timeFrame: 48 weeks of treatment
measure: 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.
timeFrame: 48 weeks of treatment
measure: Time to Virologic Failure Through 48 Weeks of Treatment, Using VL < 400 Copies/mL as the Response Criterion.
timeFrame: 48 weeks of treatment
measure: Response up to 48 Weeks Using VL < 50 Copies/mL Using Censored
timeFrame: up to 48 weeks
measure: Response up to 48 Weeks Using VL < 50 Copies/mL Using NCF
timeFrame: up to 48 weeks
measure: Response up to 48 Weeks Using VL < 50 Copies/mL Using Intent-to-treat
timeFrame: up to 48 weeks
measure: Response up to 48 Weeks Using VL < 400 Copies/mL Using Censored
timeFrame: up to 48 weeks
measure: Response up to 48 Weeks Using VL < 400 Copies/mL Using NCF
timeFrame: up to 48 weeks
measure: Response up to 48 Weeks Using VL < 400 Copies/mL Using Intent-to-treat
timeFrame: up to 48 weeks
measure: Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using Censored
timeFrame: up to 48 weeks
measure: Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using NCF
timeFrame: up to 48 weeks
measure: Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using Intent-to-treat
timeFrame: up to 48 weeks
measure: Daily Average in CD4+ Cell Count Change From Baseline at up to Week 8
timeFrame: up to week 8
measure: Daily Average in CD4+ Cell Count Change From Baseline up to Week 24
timeFrame: up to week 24
measure: Daily Average in CD4+ Cell Count Change From Baseline up to Week 48
timeFrame: up to week 48
measure: Daily Average in Viral Load Change From Baseline up to Week 8
timeFrame: up to week 8
measure: Daily Average in Viral Load Change From Baseline up to Week 24
timeFrame: up to week 24
measure: Daily Average in Viral Load Change From Baseline up to Week 48
timeFrame: up to week 48
measure: Change From Baseline in CD4+ Cell Count up to Week 48
timeFrame: up to week 48
measure: Change From Baseline in log10 Viral Load up to Week 48
timeFrame: up to week 48
measure: Occurrence of New AIDS Progression Events or Death
timeFrame: through 48 weeks of treatment
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: 1182.71.1109 Boehringer Ingelheim Investigational Site
state: California
city: Ft. Lauderdale
country: United States
facility: 1182.71.1101 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1182.71.1104 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1182.71.1115 Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: 1182.71.1108 Boehringer Ingelheim Investigational Site
state: Florida
city: Charlotte
country: United States
facility: 1182.71.1126 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Portland
country: United States
facility: 1182.71.1124 Boehringer Ingelheim Investigational Site
state: Oregon
city: Houston
country: United States
facility: 1182.71.1116 Boehringer Ingelheim Investigational Site
state: Texas
city: Longview
country: United States
facility: 1182.71.1118 Boehringer Ingelheim Investigational Site
state: Texas
city: Nassau
country: Bahamas
facility: 1182.71.1016 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1182.71.3202 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1182.71.3203 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1182.71.3205 Boehringer Ingelheim Investigational Site
city: Charleroi
country: Belgium
facility: 1182.71.3206 Boehringer Ingelheim Investigational Site
city: Vancouver
country: Canada
facility: 1182.71.1002 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Ottawa
country: Canada
facility: 1182.71.1001 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1182.71.1003 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 1182.71.1006 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 1182.71.1010 Boehringer Ingelheim Investigational Site
state: Quebec
city: Bondy
country: France
facility: 1182.71.3305A Boehringer Ingelheim Investigational Site
city: Garches
country: France
facility: 1182.71.3303A Boehringer Ingelheim Investigational Site
city: Lyon cedex 3
country: France
facility: 1182.71.3312A Boehringer Ingelheim Investigational Site
city: Lyon cedex
country: France
facility: 1182.71.3301A Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1182.71.3306A Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1182.71.3308A Boehringer Ingelheim Investigational Site
city: Tourcoing cedex
country: France
facility: 1182.71.3310A Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1182.71.4902 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1182.71.4907 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1182.71.4903 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1182.71.3002 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1182.71.3003 Boehringer Ingelheim Investigational Site
city: Piraeus
country: Greece
facility: 1182.71.3001 Boehringer Ingelheim Investigational Site
city: Antella (fi)
country: Italy
facility: 1182.71.3912 Boehringer Ingelheim Investigational Site
city: Brescia
country: Italy
facility: 1182.71.3901 Boehringer Ingelheim Investigational Site
city: Firenze
country: Italy
facility: 1182.71.3908 Boehringer Ingelheim Investigational Site
city: Palermo
country: Italy
facility: 1182.71.3916 Boehringer Ingelheim Investigational Site
city: Pavia
country: Italy
facility: 1182.71.3907 Boehringer Ingelheim Investigational Site
city: Pescara
country: Italy
facility: 1182.71.3919 Boehringer Ingelheim Investigational Site
city: Amadora
country: Portugal
facility: 1182.71.3502 Boehringer Ingelheim Investigational Site
city: Lisbon
country: Portugal
facility: 1182.71.3504 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1182.71.3503 Boehringer Ingelheim Investigational Site
city: Ponce
country: Puerto Rico
facility: 1182.71.1129 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1182.71.3401 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1182.71.3402 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat
country: Spain
facility: 1182.71.3403 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1182.71.3405 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1182.71.3407 Boehringer Ingelheim Investigational Site
city: Santiago de Compostela
country: Spain
facility: 1182.71.3408 Boehringer Ingelheim Investigational Site
city: Bangkok Noi
country: Thailand
facility: 1182.71.6601 Boehringer Ingelheim Investigational Site
city: Bangkok
country: Thailand
facility: 1182.71.6604 Boehringer Ingelheim Investigational Site
city: Chiang Mai
country: Thailand
facility: 1182.71.6605 Boehringer Ingelheim Investigational Site
city: Khon Kaen
country: Thailand
facility: 1182.71.6602 Boehringer Ingelheim Investigational Site
city: Nonthaburi
country: Thailand
facility: 1182.71.6606 Boehringer Ingelheim Investigational Site
city: Phathumwan
country: Thailand
facility: 1182.71.6603 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Elgadi MM, Piliero PJ. Boosted tipranavir versus darunavir in treatment-experienced patients: observational data from the randomized POTENT trial. Drugs R D. 2011 Dec 1;11(4):295-302. doi: 10.2165/11596340-000000000-00000.