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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00517192
• Date of registration: 15/08/2007
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim
• Public title: Comparison of TPV/r to DRV/r in Triple Class Experienced Patient With Resistance to > 1 PI
• Scientific 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
• Date of first enrolment: September 2007
• Target sample size: 40
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00517192
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Argentina, Bahamas, Belgium, Brazil, Canada, France, Germany, Greece, Italy, Mexico, Poland, Portugal, Puerto Rico, Spain, Switzerland, Thailand, United States

Contacts

• Name: Boehringer Ingelheim
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

HIV Infections

Intervention(s)

Drug: Tipranavir

Drug: Ritonavir

Drug: Darunavir

Primary Outcome(s)

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

Secondary Outcome(s)

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. [Time Frame: 48 weeks of treatment]

Response up to 48 Weeks Using VL < 50 Copies/mL Using Intent-to-treat [Time Frame: up to 48 weeks]

Response up to 48 Weeks Using VL < 50 Copies/mL Using NCF [Time Frame: up to 48 weeks]

Occurrence of New AIDS Progression Events or Death [Time Frame: through 48 weeks of treatment]

Response up to 48 Weeks Using VL < 400 Copies/mL Using NCF [Time Frame: up to 48 weeks]

Change From Baseline in CD4+ Cell Count up to Week 48 [Time Frame: up to week 48]

Daily Average in CD4+ Cell Count Change From Baseline at up to Week 8 [Time Frame: up to week 8]

Daily Average in Viral Load Change From Baseline up to Week 24 [Time Frame: up to week 24]

Daily Average in Viral Load Change From Baseline up to Week 8 [Time Frame: up to week 8]

Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using Intent-to-treat [Time Frame: up to 48 weeks]

Response up to 48 Weeks Using VL < 400 Copies/mL Using Censored [Time Frame: up to 48 weeks]

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). [Time Frame: 48 weeks of treatment]

Daily Average in CD4+ Cell Count Change From Baseline up to Week 24 [Time Frame: up to week 24]

Change From Baseline in log10 Viral Load up to Week 48 [Time Frame: up to week 48]

Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using Censored [Time Frame: up to 48 weeks]

Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using NCF [Time Frame: up to 48 weeks]

Response up to 48 Weeks Using VL < 400 Copies/mL Using Intent-to-treat [Time Frame: up to 48 weeks]

Response up to 48 Weeks Using VL < 50 Copies/mL Using Censored [Time Frame: up to 48 weeks]

Daily Average in CD4+ Cell Count Change From Baseline up to Week 48 [Time Frame: up to week 48]

Daily Average in Viral Load Change From Baseline up to Week 48 [Time Frame: up to week 48]

Time to Virologic Failure Through 48 Weeks of Treatment, Using VL < 400 Copies/mL as the Response Criterion. [Time Frame: 48 weeks of treatment]

Secondary ID(s)

1182.71

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 23/10/2009
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00517192