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

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

Status
Terminated
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00517192
Enrollment
40
Registered
2007-08-16
Start date
2007-09-30
Completion date
Unknown
Last updated
2014-05-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infections

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.

Interventions

DRUGTipranavir
DRUGDarunavir
DRUGRitonavir

Sponsors

Boehringer Ingelheim
Lead SponsorINDUSTRY

Study design

Intervention model
PARALLEL
Primary purpose
TREATMENT

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frame
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

MeasureTime frame
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 Censoredup to 48 weeks
Response up to 48 Weeks Using VL < 50 Copies/mL Using NCFup to 48 weeks
Response up to 48 Weeks Using VL < 50 Copies/mL Using Intent-to-treatup to 48 weeks
Response up to 48 Weeks Using VL < 400 Copies/mL Using Censoredup to 48 weeks
Response up to 48 Weeks Using VL < 400 Copies/mL Using NCFup to 48 weeks
Response up to 48 Weeks Using VL < 400 Copies/mL Using Intent-to-treatup to 48 weeks
Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using Censoredup to 48 weeks
Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using NCFup 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).48 weeks of treatment
Daily Average in CD4+ Cell Count Change From Baseline at up to Week 8up to week 8
Daily Average in CD4+ Cell Count Change From Baseline up to Week 24up to week 24
Daily Average in CD4+ Cell Count Change From Baseline up to Week 48up to week 48
Daily Average in Viral Load Change From Baseline up to Week 8up to week 8
Daily Average in Viral Load Change From Baseline up to Week 24up to week 24
Daily Average in Viral Load Change From Baseline up to Week 48up to week 48
Change From Baseline in CD4+ Cell Count up to Week 48up to week 48
Change From Baseline in log10 Viral Load up to Week 48up to week 48
Occurrence of New AIDS Progression Events or Deaththrough 48 weeks of treatment
Response up to 48 Weeks Using at Least a 1 log10 Reduction in Viral Load From Baseline Using Intent-to-treatup to 48 weeks

Countries

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

Participant flow

Participants by arm

ArmCount
Tipranavir 500 mg/Ritonavir 200 mg
Tipranavir (TPV) 250 mg soft gelatin capsules Ritonavir (RTV) 100 mg soft gelatin capsules dose: 500 mg TPV/200 mg RTV, twice daily mode of admin.: Oral
19
Darunavir 600 mg/Ritonavir 100 mg
Prezista® (DRV) 300 mg tablets Ritonavir (RTV) 100 mg soft gelatin capsules dose: 600 mg DRV/100 mg RTV, twice daily mode of admin.: Oral
20
Total39

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event11
Overall StudyEarly termination of the trial1618
Overall StudyLost to Follow-up11
Overall StudyWithdrawal by Subject10

Baseline characteristics

CharacteristicTipranavir 500 mg/Ritonavir 200 mgDarunavir 600 mg/Ritonavir 100 mgTotal
Age, Continuous44.3 Years
STANDARD_DEVIATION 6.1
43.1 Years
STANDARD_DEVIATION 6.2
43.6 Years
STANDARD_DEVIATION 6.1
Sex: Female, Male
Female
4 Participants3 Participants7 Participants
Sex: Female, Male
Male
15 Participants17 Participants32 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
12 / 197 / 20
serious
Total, serious adverse events
0 / 192 / 20

Outcome results

Primary

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

Change From Baseline in CD4+ Cell Count up to Week 48

Time frame: up to week 48

Secondary

Change From Baseline in log10 Viral Load up to Week 48

Time frame: up to week 48

Secondary

Daily Average in CD4+ Cell Count Change From Baseline at up to Week 8

Time frame: up to week 8

Secondary

Daily Average in CD4+ Cell Count Change From Baseline up to Week 24

Time frame: up to week 24

Secondary

Daily Average in CD4+ Cell Count Change From Baseline up to Week 48

Time frame: up to week 48

Secondary

Daily Average in Viral Load Change From Baseline up to Week 24

Time frame: up to week 24

Secondary

Daily Average in Viral Load Change From Baseline up to Week 48

Time frame: up to week 48

Secondary

Daily Average in Viral Load Change From Baseline up to Week 8

Time frame: up to week 8

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.

Time frame: 48 weeks of treatment

Secondary

Occurrence of New AIDS Progression Events or Death

Time frame: through 48 weeks of treatment

Secondary

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

Secondary

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

Secondary

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

Secondary

Response up to 48 Weeks Using VL < 400 Copies/mL Using Censored

Time frame: up to 48 weeks

Secondary

Response up to 48 Weeks Using VL < 400 Copies/mL Using Intent-to-treat

Time frame: up to 48 weeks

Secondary

Response up to 48 Weeks Using VL < 400 Copies/mL Using NCF

Time frame: up to 48 weeks

Secondary

Response up to 48 Weeks Using VL < 50 Copies/mL Using Censored

Time frame: up to 48 weeks

Secondary

Response up to 48 Weeks Using VL < 50 Copies/mL Using Intent-to-treat

Time frame: up to 48 weeks

Secondary

Response up to 48 Weeks Using VL < 50 Copies/mL Using NCF

Time frame: up to 48 weeks

Secondary

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

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

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026