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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00517192
• Other study ID #: 1182.71
• Status: Terminated
• Phase: Phase 3
• First received: August 15, 2007
• Last updated: April 25, 2014
• Start date: September 2007

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPCanada: Health Canada (TPD)France: AFSSAPSGermany: BfArM-Bundesinstitut fuer Arzneimittel und Medizinprodukte (Federal Authorities for Drugs and MedicaGreece: National Organization for Medicines (EOF) National Ethics CommitteeItaly: Comitato Etico Azienda Spedali Civili di BresciaPortugal: INFARMED I.P. Parque da Saúde de Lisboa Av. do Brasil, nº 53 1749-004 LisboaSpain: Ministry of HealthThailand: Ministry of Public HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Tipranavir

• Darunavir

• Ritonavir

Locations

Country	Name	City	State
Bahamas	1182.71.1016 Boehringer Ingelheim Investigational Site	Nassau
Belgium	1182.71.3202 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1182.71.3203 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1182.71.3205 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1182.71.3206 Boehringer Ingelheim Investigational Site	Charleroi
Canada	1182.71.1003 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1182.71.1006 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1182.71.1010 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1182.71.1001 Boehringer Ingelheim Investigational Site	Ottawa	Ontario
Canada	1182.71.1002 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
France	1182.71.3305A Boehringer Ingelheim Investigational Site	Bondy
France	1182.71.3303A Boehringer Ingelheim Investigational Site	Garches
France	1182.71.3301A Boehringer Ingelheim Investigational Site	Lyon cedex
France	1182.71.3312A Boehringer Ingelheim Investigational Site	Lyon cedex 3
France	1182.71.3306A Boehringer Ingelheim Investigational Site	Paris
France	1182.71.3308A Boehringer Ingelheim Investigational Site	Paris
France	1182.71.3310A Boehringer Ingelheim Investigational Site	Tourcoing cedex
Germany	1182.71.4902 Boehringer Ingelheim Investigational Site	Berlin
Germany	1182.71.4907 Boehringer Ingelheim Investigational Site	Frankfurt
Germany	1182.71.4903 Boehringer Ingelheim Investigational Site	Mainz
Greece	1182.71.3002 Boehringer Ingelheim Investigational Site	Athens
Greece	1182.71.3003 Boehringer Ingelheim Investigational Site	Athens
Greece	1182.71.3001 Boehringer Ingelheim Investigational Site	Piraeus
Italy	1182.71.3912 Boehringer Ingelheim Investigational Site	Antella (fi)
Italy	1182.71.3901 Boehringer Ingelheim Investigational Site	Brescia
Italy	1182.71.3908 Boehringer Ingelheim Investigational Site	Firenze
Italy	1182.71.3916 Boehringer Ingelheim Investigational Site	Palermo
Italy	1182.71.3907 Boehringer Ingelheim Investigational Site	Pavia
Italy	1182.71.3919 Boehringer Ingelheim Investigational Site	Pescara
Portugal	1182.71.3502 Boehringer Ingelheim Investigational Site	Amadora
Portugal	1182.71.3504 Boehringer Ingelheim Investigational Site	Lisbon
Portugal	1182.71.3503 Boehringer Ingelheim Investigational Site	Porto
Puerto Rico	1182.71.1129 Boehringer Ingelheim Investigational Site	Ponce
Spain	1182.71.3401 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1182.71.3402 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1182.71.3403 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat
Spain	1182.71.3405 Boehringer Ingelheim Investigational Site	Madrid
Spain	1182.71.3407 Boehringer Ingelheim Investigational Site	Madrid
Spain	1182.71.3408 Boehringer Ingelheim Investigational Site	Santiago de Compostela
Thailand	1182.71.6604 Boehringer Ingelheim Investigational Site	Bangkok
Thailand	1182.71.6601 Boehringer Ingelheim Investigational Site	Bangkok Noi
Thailand	1182.71.6605 Boehringer Ingelheim Investigational Site	Chiang Mai
Thailand	1182.71.6602 Boehringer Ingelheim Investigational Site	Khon Kaen
Thailand	1182.71.6606 Boehringer Ingelheim Investigational Site	Nonthaburi
Thailand	1182.71.6603 Boehringer Ingelheim Investigational Site	Phathumwan
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	1182.71.1101 Boehringer Ingelheim Investigational Site	Ft. Lauderdale	Florida
United States	1182.71.1116 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1182.71.1118 Boehringer Ingelheim Investigational Site	Longview	Texas
United States	1182.71.1104 Boehringer Ingelheim Investigational Site	Miami	Florida
United States	1182.71.1115 Boehringer Ingelheim Investigational Site	Miami	Florida
United States	1182.71.1124 Boehringer Ingelheim Investigational Site	Portland	Oregon
United States	1182.71.1108 Boehringer Ingelheim Investigational Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Bahamas,  Belgium,  Canada,  France,  Germany,  Greece,  Italy,  Portugal,  Puerto Rico,  Spain,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Time to Virologic Failure Through 48 Weeks of Treatment, Using VL < 400 Copies/mL as the Response Criterion.		48 weeks of treatment
Secondary	Response up to 48 Weeks Using VL < 50 Copies/mL Using Censored		up to 48 weeks
Secondary	Response up to 48 Weeks Using VL < 50 Copies/mL Using NCF		up to 48 weeks
Secondary	Response up to 48 Weeks Using VL < 50 Copies/mL Using Intent-to-treat		up to 48 weeks
Secondary	Response up to 48 Weeks Using VL < 400 Copies/mL Using Censored		up to 48 weeks
Secondary	Response up to 48 Weeks Using VL < 400 Copies/mL Using NCF		up to 48 weeks
Secondary	Response up to 48 Weeks Using VL < 400 Copies/mL Using Intent-to-treat		up to 48 weeks
Secondary	Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using Censored		up to 48 weeks
Secondary	Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using NCF		up to 48 weeks
Secondary	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
Secondary	Daily Average in CD4+ Cell Count Change From Baseline at up to Week 8		up to week 8
Secondary	Daily Average in CD4+ Cell Count Change From Baseline up to Week 24		up to week 24
Secondary	Daily Average in CD4+ Cell Count Change From Baseline up to Week 48		up to week 48
Secondary	Daily Average in Viral Load Change From Baseline up to Week 8		up to week 8
Secondary	Daily Average in Viral Load Change From Baseline up to Week 24		up to week 24
Secondary	Daily Average in Viral Load Change From Baseline up to Week 48		up to week 48
Secondary	Change From Baseline in CD4+ Cell Count up to Week 48		up to week 48
Secondary	Change From Baseline in log10 Viral Load up to Week 48		up to week 48
Secondary	Occurrence of New AIDS Progression Events or Death		through 48 weeks of treatment

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