A Phase 2B Multicenter, Randomized, Comparative Trial Of UK-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleos(t)Ide Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced HIV-1 Infected Subjects With Evidence Of NNRTI Resistant HIV-1

November 7, 2018 updated by: Pfizer

A Phase 2b Multicenter, Randomized, Comparative Trial Of Uk-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleotide/Nucleoside Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced Hiv-1 Infected Subjects With Evidence Of Nnrti Resistant Hiv-1

This is a 96 week study to determine if UK- 453,061 in combination with Darunavir /ritonavir and a Nucleos(t)ide Reverse Transcriptase inhibitor is as efficacious, safe and tolerable as etravirine in combination with Darunavir /ritonavir and a Nucleos(t)ide Reverse Transcriptase inhibitor in HIV-1 infected patients who have been previously treated with antiretroviral drugs and have NNRTI resistance mutations.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The trial was terminated on 12 April, 2012 due to lack of efficacy at the Week 24 analysis. The decision to terminate the trial was not based on any safety concerns.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
105

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • PR
      • Curitiba, PR, Brazil, 80240-280
        • Instituto A.Z. de Pesquisa e Ensino
    • RJ
      • Nova Iguacu, RJ, Brazil, 26030-381
        • Hospital Geral de Nova Iguaçu
    • RS
      • PoA, RS, Brazil, 91350-200
        • Hospital Nossa Senhora da Conceicao
    • SP
      • Campinas, SP, Brazil, 13015-080
        • Instituto de Infectologia Campinas
      • Sao Paulo, SP, Brazil, 04121-000
        • Centro de Referência e Treinamento DST/AIDS
      • Sao Paulo, SP, Brazil, 04231-030
        • Hospital Heliopolis
  • Germany
      • Koeln, Germany, 50937
        • Klinikum der Universitaet zu Koeln, Klinik I fuer Innere Medizin
  • Italy
      • Bologna, Italy, 40138
        • Unita' Operativa Malattie Infettive
      • Roma, Italy, 00184
        • U.O.S. Immunologia Clinica
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • University Malaya Medical Centre
    • Kelantan
      • Kota Bharu, Kelantan, Malaysia, 15586
        • Hospital Raja Perempuan Zainab Ii
  • Poland
      • Szczecin, Poland, 71-455
        • Oddzial do Leczenia HIV
      • Warszawa, Poland, 01-201
        • SPZOZ Wojewodzki Szpital Zakazny
  • Portugal
      • Coimbra, Portugal, 3000-075
        • Hospitais da universidade de Coimbra
      • Lisboa, Portugal, 1169-050
        • Centro Hospitalar de Lisboa - Zona Central - Hospital Santo António Capuchos
      • Lisboa, Portugal, 1349-019
        • Centro Hospitalar de Lisboa Ocidental, EPE.
      • Porto, Portugal, 4200-319
        • Hospital Sao Joao
      • Porto, Portugal, 4369-004
        • Hospital de Joaquim Urbano
  • Puerto Rico
      • Bayamon, Puerto Rico, 00959
        • Innovative Care PSC
      • Ponce, Puerto Rico, 00717-1563
        • Ararat Research Center
      • Rio Piedras, Puerto Rico, 00935
        • University of Puerto Rico - Medical Sciences Campus - Puerto Rico Medical Center
      • San Juan, Puerto Rico, 00909
        • HOPE Clinical Research
      • San Juan, Puerto Rico, 00935
        • UPR-CTU Pharmacy
  • South Africa
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 1818
        • Soweto Clinical Trials Centre
      • Johannesburg, Gauteng, South Africa, 2193
        • University of Witwatersrand
    • Johannesburg
      • Soweto, Johannesburg, South Africa, 2013
        • Chris Hani Baragwanath Hospital
    • Kwazulu-natal
      • Dundee, Kwazulu-natal, South Africa, 3000
        • Dr. J Fourie Medical Centre
      • Durban, Kwazulu-natal, South Africa, 4001
        • 203 Maxwell Centre
    • Western CAPE
      • Cape Town, Western CAPE, South Africa, 7780
        • Willowmead Medical Center
      • Cape Town, Western CAPE, South Africa, 7925
        • Desmond Tutu HIV Foundation
  • Spain
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
  • Taiwan
      • Kaohsiung County, Taiwan, 82445
        • Department of Infectious Disease, E-Da Hospital
      • Taipei, Taiwan
        • Veterans General Hospital - Taipei
  • Ukraine
      • Donetsk, Ukraine, 83045
        • Donetsk Regional Center of AIDSs prophylaxis and control
      • Lugansk, Ukraine, 91045
        • Lugansk Regional Center of AIDS prophylaxis and control
    • Vinnitsa District, Vinnitsa Region
      • Berezyna, Vinnitsa District, Vinnitsa Region, Ukraine, 23222
        • Vinnitsa Regional center for AIDS Prevention and Control
  • United Kingdom
      • Edinburgh, United Kingdom, EH4 2XU
        • Western General Hospital
      • Edinburgh, United Kingdom, EH3 9HA
        • Royal Infirmary GUM Clinic
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
    • EAST Sussex
      • Brighton, EAST Sussex, United Kingdom, BN2 1ES
        • Brighton and Sussex University Hospitals NHS Trust
    • Greater Manchester
      • Crumpsall, Greater Manchester, United Kingdom, M8 5RB
        • North Manchester General Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90028
        • Jeffrey Goodman Special Care Clinic
      • Los Angeles, California, United States, 90069
        • Office of Anthony Mills, MD, Inc.
      • Sacramento, California, United States, 95817
        • University of California Davis Medical Center
      • Sacramento, California, United States, 95814
        • CARES
      • San Francisco, California, United States, 94121
        • San Francisco Veterans Affairs Medical Center
    • Florida
      • Miami, Florida, United States, 33133
        • The Kinder Medical Group
      • Miami, Florida, United States, 33137
        • Care Resource
      • Orlando, Florida, United States, 32803
        • Orlando Immunology Center
      • Pensacola, Florida, United States, 32504
        • Infectious Diseases Associates of Northwest Florida, PA
      • Tampa, Florida, United States, 33602
        • Hillsborough County Health Department
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • AIDS Research Consortium of Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Ruth M. Rothstein CORE Center
    • New York
      • East Meadow, New York, United States, 11554
        • Nassau University Medical Center
      • Mount Vernon, New York, United States, 10550
        • Greiger Clinic
    • North Carolina
      • Huntersville, North Carolina, United States, 28078
        • Rosedale Infectious Diseases
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0405
        • University of Cincinnati Medical Center
    • Texas
      • Bellaire, Texas, United States, 77401
        • Saint Hope Foundation - Bellaire Clinic
      • Conroe, Texas, United States, 77301
        • Saint Hope Foundation - Conroe Clinic
      • Dallas, Texas, United States, 75204
        • Nicholaos C. Bellos, MD, PA
      • Dallas, Texas, United States, 75235
        • University of Texas Southwestern Medical Center at Dallas
      • Stafford, Texas, United States, 77477
        • Saint Hope Foundation - Stafford Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female at least 18 years of age available for a follow-up period of at least 96 weeks.
  • HIV 1 RNA viral load of greater then 500 copies/mL.
  • Negative urine pregnancy test.

Exclusion Criteria:

  • Suspected or documented active, untreated HIV-1 related opportunistic infection or other condition requiring acute therapy at the time of randomization.
  • Subjects with acute Hepatitis B and/or C within 30 days of randomization.
  • Previous use of Darunavir or etravirine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Comparator
Drug: Etravirine
Etravirine 200 mg BID + one optimized NRTI + darunavir/ritonavir.
Experimental: UK- 453,061 Dose One
Drug: UK-453,061 Dose 1
UK 453,061 750 mg QD + one optimized NRTI + darunavir/ritonavir.
Experimental: UK- 453,061 Dose Two
Drug: UK-453,061 Dose 2
UK 453,061 1000 mg QD + one optimized NRTI + darunavir/ritonavir.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/Milliliter (mL) at Week 24
Time Frame: Week 24
Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).
Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With HIV-1 RNA Levels <50 Copies/mL at Week 48 and 96
Time Frame: Weeks 48, 96
Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).
Weeks 48, 96
Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96
Time Frame: Week 24, 48, 96
Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).
Week 24, 48, 96
Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96
Time Frame: Baseline, Week 24, 48, 96
Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5). For the log10 scale, all the HIV-1 RNA levels were log10 transformed prior to the average calculations. Baseline value calculated as average of measurements collected prior to and including Day 1 pre-dose.
Baseline, Week 24, 48, 96
Time-Averaged Difference (TAD) in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96
Time Frame: Week 24, 48, 96
TAD was calculated as (area under the curve of HIV-1 RNA levels [log10 copies/mL] from baseline to the time point of interest divided by time period in weeks) minus baseline HIV-1 RNA level (log10 copies/mL). Baseline value calculated as average of measurements collected at prior to and including Day 1 pre-dose. Due to early termination of the study decision was made not to derive TAD results for Week 96.
Week 24, 48, 96
Percentage of Participants With Response as Determined by the Time to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96
Time Frame: Week 24, 48, 96
TLOVR50 response (50 denotes lower limit of quantification [LLOQ] of assay=50 copies/mL): compliment to TLOVR50 failure. TLOVR50 failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of drug; lost to follow-up; new ARV drug; met treatment failure [TF] criteria). TF: an increase of at least (>=)3 times the baseline plasma HIV-1 RNA level at Week 2 or thereafter; failure to achieve HIV-1 RNA level <50 copies/mL at Week 24; starting at Week 2, an increase in HIV-1 RNA level to detectable levels (>50 copies/mL); HIV-1 RNA <1 log10 decrease from baseline at Week 4 or thereafter. TF were confirmed by second measurement >=14 days after first. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.
Week 24, 48, 96
Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96
Time Frame: Baseline, Week 24, 48, 96
Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.
Baseline, Week 24, 48, 96
Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96
Time Frame: Baseline, Week 24, 48, 96
Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.
Baseline, Week 24, 48, 96
Number of Participants With Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Resistance-Associated Mutations (RAMs) and/or Phenotypic Susceptibility at Time of Treatment Failure Through Week 48
Time Frame: Baseline through Week 48
Genotypic and phenotypic resistance to NNRTIs based on International Acquired Immunodeficiency Syndrome (AIDS) Society, United States of America (IAS-USA) RAM guidelines were evaluated using Monogram Biosciences PhenoSenseGT Assay at Baseline. This was then repeated for all participants with HIV-1 viral load >500 copies/mL at treatment failure, up to Week 48.
Baseline through Week 48
Number of Participants With Laboratory Test Abnormalities
Time Frame: Baseline up to Week 48 or early termination
Laboratory analysis included blood chemistry, hematology and urinalysis.
Baseline up to Week 48 or early termination
Population Pharmacokinetics (PK) of Lersivirine
Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48
Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48
Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin)
Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48
Simple quartile exposure analysis of success rate (viral load <50 copies/mL) versus median Cmin assesses the exposure response relationship. Percentage of participants with HIV-1 RNA level <50 copies/mL at median Cmin quartile were planned to be reported.
Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 25, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 18, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 18, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 4, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • A5271022
  • 2007-004392-19 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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