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

Sponsor:	Tibotec, Inc
Collaborator:	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

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.

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Enfuvirtide Darunavir Etravirine Darunavir ethanolate

U.S. FDA Resources

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 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Evaluation of the Proportion of Patients Who Have Viral Load Measurements <50 Copies/ml at 2, 4, 8, 12, 16, 24, 36 and 48 Weeks After Switching to DRV/r and ETR, Missing Equals Failure. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks (Intent To Treat (ITT)-Last Observation Carried Forward (LOCF)). [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks (Intent To Treat (ITT)-Last Observation Carried Forward (LOCF)). [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Median Change From Baseline in Triglycerides (LOCF). ITT Population. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Median Change From Baseline in Total Cholesterol(LOCF). ITT Population. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Median Change From Baseline in LDL Cholesterol (LOCF). ITT Population. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Median Change From Baseline in HDL Cholesterol (LOCF). ITT Population. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Median Change From Baseline in TC/HDL Ratio (LOCF). ITT Population. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Median Change From Baseline in Glucose (LOCF). ITT Population. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Enrollment:	10
Study Start Date:	April 2007
Study Completion Date:	October 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

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

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

No publications provided

Responsible Party:	Tibotec Therapeutics Clinical Affairs, a Division of Centocor Ortho Biotech Services, LLC. ( Vice President Clinical Affairs )
Study ID Numbers:	CR011866, TMC114HIV3009
Study First Received:	April 13, 2007
Results First Received:	October 2, 2009
Last Updated:	October 2, 2009
ClinicalTrials.gov Identifier:	NCT00460746 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Tibotec, Inc:

darunavir
enfuvirtide
PREZISTA
TMC125
Protease Inhibitor
Immunodeficiency Virus, Human

TMC114
HIV
AIDS
Non-Nucleoside Reverse Transcriptase Inhibitor
Treatment Experienced

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
Anti-HIV Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Antiviral Agents
Darunavir
Enfuvirtide

Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Ritonavir
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors
HIV Fusion Inhibitors

ClinicalTrials.gov processed this record on November 27, 2009