TerminatedNCT00517192Updated May 14, 2014Results posted

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

A Phase 3 interventional study of Tipranavir and Darunavir in HIV Infections, sponsored by Boehringer Ingelheim. Terminated at 54 sites in 12 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-05-14.

Sponsored by Boehringer Ingelheim · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 40
Ages: 18 Years and older
Sex: All

Study 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.

Conditions studied

HIV Infections

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In context

HIV Infections

4,734 studies on the registry are indexed under HIV Infections; 244 are open to participants now.

This study's enrollment of 40 is below the median of 80 across 3,489 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,304 studies on the registry; 62 are open to participants now.

Of its 167 completed or terminated interventional studies of FDA-regulated products, 123 (74%) have results posted.

Browse Boehringer Ingelheim studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria:

Signed prior to trial participation.
-1 infected male or female >18 years of age.
Three-class (NRTI, NNRTI, and PI) treatment-experienced patients (a minimum of 3-months duration for each class or documented class /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.
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.
Patient has been on their current (failing) PI-containing regimen for at least 8 weeks prior to randomization.
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.
Any baseline will be allowed.
performance score of ≥ 70.
Acceptable screening laboratory values that indicate adequate baseline organ function. Laboratory values are considered acceptable if the following apply:
- ≤2.5 x 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.
Willingness to initiate CD4+ cell count-guided chemoprophylaxis to prevent opportunistic infections.
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:

Previous use of Tipranavir (TPV) or Darunavir (DRV).
Full genotypic resistance (reported as minimal response) to Tipranavir (TPV) or Darunavir (DRV) on screening virtual phenotype:
Female patient of 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 or requires ethinyl estradiol administration. Barrier methods of contraception include diaphragm with spermicidal substance, condom for females, cervical caps and condoms.
History of Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any .
Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit.
Use of immunomodulatory drugs (such as interferon, cyclosporin, hydroxyurea and interleukin 2) within 30 days prior to randomization.
Current use of systemic cytotoxic chemotherapy.
All listed in the product monographs of Aptivus, Prezista and Norvir.

Terms in these criteria, in plain language(11)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

CD4 count

The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Study design

Phase: Phase 3
Primary purpose: Treatment
Intervention model: Parallel assignment
Enrollment: 40 participants (actual)

Interventions

What researchers measure

Primary outcomes

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 outcomes

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

Results

Posted Oct 23, 2009

Participant flow

Participant flow — Overall Study
Milestone	Tipranavir 500 mg/Ritonavir 200 mg	Darunavir 600 mg/Ritonavir 100 mg
Started	19	20
Completed	0	0
Not completed	19	20
Withdrew: Adverse event	1	1
Withdrew: Lost to follow-up	1	1
Withdrew: Withdrawal by subject	1	0
Withdrew: Early termination of the trial	16	18

Outcome measures

PrimaryTime 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