Enfuvirtide/Current Protease Inhibitor Switch to PREZISTA (Darunavir)/Ritonavir + TMC125 in HIV Patients With Enfuvirtide Side Effects. - Full Text View

Sponsors and Collaborators:	Tibotec, Inc Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by:	Tibotec, Inc
ClinicalTrials.gov Identifier:	NCT00460746

Purpose

The purpose of this study is to examine the safety, tolerability, and effectiveness of darunavir/ritonavir combined with TMC125 when current protease inhibitor(s), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI(s)) and enfuvirtide are replaced by darunavir/ritonavir and TMC125 in HIV positive patients who can no longer tolerate enfuvirtide and are experiencing viral suppression. Other antiviral drugs in the regimen are to remain unchanged.

Condition	Intervention	Phase
HIV	Drug: TMC125, Darunavir; Ritonavir	Phase III

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Darunavir Darunavir ethanolate Enfuvirtide Etravirine

U.S. FDA Resources

Study Type:

Interventional

Study Design:

Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Official Title:

Open Label Phase 3b, 48 wk Pilot Study of the Antiviral Efficacy and Tolerability of Combination of PREZISTA/r and TMC125 When Substituted for Enfuvirtide, Current Protease Inhibitor(s) and NNRTI(s) in Antiretroviral Resistant Patients With Viral Suppression But Who Are Intolerant of Enfuvirtide.

Further study details as provided by Tibotec, Inc:

Primary Outcome Measures:

Evaluation of the proportion of patients who maintain plasma HIV viral load measurements <= 400 copies/ml at week 4, 8, 12, 16, 24, 36 and 48 weeks after switching to PREZISTA (darunavir)/ritonavir and TMC125. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Evaluation of the proportion of patients who have viral load measurements <50 copies/ml and assessment of CD4 cell count changes; Time to virologic failure; Assessment of lipid changes; Resistance Patterns; Patient Adherence; Quality of Life [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:

40

Study Start Date:

April 2007

Estimated Study Completion Date:

March 2009

Arms	Assigned Interventions
001: Experimental	Drug: TMC125, Darunavir; Ritonavir TMC125-200mg two times a day for 48 weeks; Darunavir -200mg two times a day for 48 weeks; Ritonavir-100mg two times a day for 48 weeks;

Detailed Description:

This is a multi-center, open-label (doctors and patients know which drug is being given), Phase IIIb clinical trial to evaluate the effectiveness, safety and tolerability of the combination of PREZISTA (darunavir)/ritonavir and TMC125 when substituted for enfuvirtide, current protease inhibitor(s) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI(s)) in antiretroviral resistant patients with viral suppression but who are intolerant of enfuvirtide. This study will be conducted in the U.S. at up to 5 sites where 40 patients will receive PREZISTA (darunavir) /ritonavir twice daily (600/100mg) and TMC125 (200 mg) twice daily over a 48-week treatment period. The study will consist of a total of 11 patient visits. At the screening visit (Week -1 to -6) blood will be collected from patients to determine eligibility. Once all data are available to determine the eligibility of the patient, the baseline visit will be scheduled and trial treatment initiated at this visit. The Baseline Visit (Day 1) will be followed by a 48-week treatment period. The patient will be evaluated at Weeks 2, 4, 8, 12, 16, 24, 36, and 48. Patients will be asked to return for a 2-week follow up visit at Week 50. Treatment will include PREZISTA (darunavir) /ritonavir and TMC125 plus continued nucleosides. The patient must continue all existing nucleosides in their background regimen for the duration of the study. During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits.

Study patients will receive oral (by mouth) PREZISTA (darunavir) 600 mg and 100 mg of ritonavir twice a day in combination with TMC125 200mg orally twice a day for 48 weeks.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Documented HIV-1 positive
History of drug resistance or antiretroviral failure while receiving each of three drug classes: Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) and (protease inhibitors) PIs
On a PI containing regimen with enfuvirtide with HIV viral load (VL) < 400 copies/mL for 6 months or longer
Continuously using the same PI regimen for 4 months prior to Screening
Decline to continue enfuvirtide or their physician recommends discontinuation due to injection site reactions that persist despite optimal technique and training with available methods of administration or loss of sites for injection due to tissue nodules and hardening

Exclusion Criteria:

No use of any drug contraindicated in the current US package insert for PREZISTA (darunavir) or in the investigators brochure for TMC125
No prior or current therapy with PREZISTA (darunavir) or TMC125
No prior genotypic results demonstrating 3 or more darunavir resistance-associated mutations associated with diminished response to darunavir (V11I, V32I, L33F, I47V, I50V, I54L, I54M, G73S, L76V, I84V or L89V). Patients with > 3 darunavir resistance-associated mutations with available darunavir phenotypes, may be enrolled if the resistance phenotype demonstrates: Fold Change (FC) <10 to darunavir by PhenoSense GT (Monogram Biosciences) or FC <10 to darunavir by Antivirogram (Virco, BVBA) or FC <3.4 to darunavir by vircoTYPE (Virco BVBA)
AST or ALT >5 times ULN
Calculated CrCl < 30 ml/min

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00460746

Locations

United States, California
Peter J. Ruane MD, Inc.
Los Angeles, California, United States, 90036

Sponsors and Collaborators

Tibotec, Inc

Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Investigators

Study Director:

Tibotec, Inc. Clinical Trial

Tibotec, Inc

More Information

Responsible Party:

Tibotec Therapeutics Clinical Affairs, a Division of Ortho Biotech Clinical Affairs, LLC ( Vice President Clinical Affairs )

Study ID Numbers:

CR011866, TMC114HIV3009

First Received:

April 13, 2007

Last Updated:

December 18, 2008

ClinicalTrials.gov Identifier:

NCT00460746

Health Authority:

United States: Food and Drug Administration

Keywords provided by Tibotec, Inc:

TMC114
Non-Nucleoside Reverse Transcriptase Inhibitor
TMC125
Protease Inhibitor
PREZISTA
enfuvirtide

Immunodeficiency Virus, Human
AIDS
HIV
darunavir
Treatment Experienced

Study placed in the following topic categories:

Virus Diseases
Ritonavir
HIV Infections
Acquired Immunodeficiency Syndrome

Enfuvirtide
Darunavir
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Enzyme Inhibitors
Antiviral Agents
Pharmacologic Actions
HIV Fusion Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on January 07, 2009