HIVPhase 3NCT00460746

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

A Phase 3 study testing TMC125, Darunavir; Ritonavir in people with HIV, run by Tibotec, Inc at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV
What is being tested?: TMC125, Darunavir; Ritonavir
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteUnited States
Study dates: May 2007to Oct 2008
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Study site
Los Angeles, California

Other trials in United States

About this 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.

Read the 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.

Conditions: HIV
Being tested: TMC125, Darunavir; Ritonavir
Keywords: HIV, AIDS, Immunodeficiency Virus, Human, PREZISTA, darunavir, TMC114, TMC125, Protease Inhibitor, Non-Nucleoside Reverse Transcriptase Inhibitor, enfuvirtide, Treatment Experienced
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TMC125, Darunavir; RitonavirDrug
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;

Study groups in NCT00460746
Study group	Role	What they receive
001	Experimental	TMC125, Darunavir; RitonavirTMC125-200mg 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; Receives: Drug: TMC125, Darunavir; Ritonavir

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 48 weeks

Secondary outcomes (9)

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.
Measured: 48 weeks
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Measured: Week 48
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Measured: Week 48
Median Change From Baseline in Triglycerides at Week 48.
Measured: Week 48
Median Change From Baseline in Total Cholesterol at Week 48.
Measured: Week 48
Median Change From Baseline in LDL Cholesterol at Week 48.
Measured: Week 48
Median Change From Baseline in HDL Cholesterol.
Measured: Week 48
Median Change From Baseline in Total Cholesterol (TC) / High Denisty Lipoprotein (HDL) Ratio at Week 48.
Measured: Week 48
Median Change From Baseline in Glucose at Week 48.
Measured: Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2007Oct 2008

First posted16 Apr 2007 (estimated)
Study startMay 2007
Primary completionOct 2008
Study completionOct 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIVStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00460746
Sponsor's protocol ID: CR011866
Other IDs: TMC114HIV3009
Status last verified: Jul 2013
First submitted: 13 Apr 2007
Last updated: 31 Jul 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 31 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

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.
ClinicalTrials.gov ID: NCT00460746
Acronym / sponsor ID: CR011866
Conditions: HIV
Keywords: HIV, AIDS, Immunodeficiency Virus, Human, PREZISTA, darunavir, TMC114, TMC125, Protease Inhibitor
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 10 participants (actual)
Lead sponsor: Tibotec, IncIndustry (pharma, biotech, devices)
Collaborators: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Study start: May 2007
Primary completion: Oct 2008 (actual)
Study completion: Oct 2008 (actual)
First posted: 16 Apr 2007 (estimated)
Results: Posted 10 Nov 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
001	Experimental	Drug: TMC125, Darunavir; RitonavirTMC125, Darunavir; RitonavirTMC125-200mg 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;

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TMC125, Darunavir; RitonavirTMC125-200mg 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;	Drug	001

Primary outcome

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

9 secondary outcomes

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
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline at 4, 8, 12, 16, 24, 36 and 48 Weeks.
Time frame: Week 48
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Mean Changes From Baseline at 4, 8, 12, 16, 24,36 and 48 Weeks.
Time frame: Week 48
Median Change From Baseline in Triglycerides at Week 48.
Time frame: Week 48
Median Change From Baseline in Total Cholesterol at Week 48.
Time frame: Week 48
Median Change From Baseline in LDL Cholesterol at Week 48.
Time frame: Week 48
Median Change From Baseline in HDL Cholesterol.
Time frame: Week 48
Median Change From Baseline in Total Cholesterol (TC) / High Denisty Lipoprotein (HDL) Ratio at Week 48.
Time frame: Week 48
Median Change From Baseline in Glucose at Week 48.
Time frame: Week 48

Results and safety

Results posted to the registry on 10 Nov 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Darunavir(TMC114)/Eravirine(TMC125)	10	8

Primary outcome: 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. Number. Unit: percentage of participants

Measure	Darunavir(TMC114)/Eravirine(TMC125) n = 10
Baseline (Day 1)	100
Week 2	100
Week 4	100
Week 8	90
Week 12	80
Week 16	90
Week 24	90
Week 36	90

Population analysed: ITT population. One subject (001) who discontinued due to adverse events had a VL \< 50 copies/mL at Week 4. Another subject (013) who was lost to follow-up had VL \<50 copies/mL through Week 36.

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Darunavir(TMC114)/Eravirine(TMC125)	1 of 10 (10%)	10 of 10 (100%)	Not reported

Limitations and caveats (from the sponsor): Conclusions on efficacy and safety are limited as the target enrollment of 40 subjects was not reached due to a shortage of eligible subjects.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Tibotec, Inc. Clinical Trial study director

Tibotec, Inc

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TMC125, Darunavir; Ritonavir in people with HIV, run by Tibotec, Inc at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Nov 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00460746.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2013.