Clinical trial NCT00823979: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV-1
Keywords: HIV-1 NNRTI Treatment Experienced
may have Protease inhibitor experience
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-01-16
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/Milliliter (mL) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA Levels <50 Copies/mL at Week 48 and 96
timeFrame: Weeks 48, 96
measure: Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96
timeFrame: Week 24, 48, 96
measure: Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96
timeFrame: Baseline, Week 24, 48, 96
measure: Time-Averaged Difference (TAD) in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96
timeFrame: Week 24, 48, 96
measure: Percentage of Participants With Response as Determined by the Time to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96
timeFrame: Week 24, 48, 96
measure: Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96
timeFrame: Baseline, Week 24, 48, 96
measure: Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96
timeFrame: Baseline, Week 24, 48, 96
measure: 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
timeFrame: Baseline through Week 48
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline up to Week 48 or early termination
measure: Population Pharmacokinetics (PK) of Lersivirine
timeFrame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48
measure: Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin)
timeFrame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jeffrey Goodman Special Care Clinic
state: California
city: Los Angeles
country: United States
facility: Office of Anthony Mills, MD, Inc.
state: California
city: Sacramento
country: United States
facility: CARES
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: San Francisco Veterans Affairs Medical Center
state: California
city: Miami
country: United States
facility: The Kinder Medical Group
state: Florida
city: Miami
country: United States
facility: Care Resource
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Pensacola
country: United States
facility: Infectious Diseases Associates of Northwest Florida, PA
state: Florida
city: Tampa
country: United States
facility: Hillsborough County Health Department
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Ruth M. Rothstein CORE Center
state: Illinois
city: East Meadow
country: United States
facility: Nassau University Medical Center
state: New York
city: Mount Vernon
country: United States
facility: Greiger Clinic
state: New York
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Bellaire
country: United States
facility: Saint Hope Foundation - Bellaire Clinic
state: Texas
city: Conroe
country: United States
facility: Saint Hope Foundation - Conroe Clinic
state: Texas
city: Dallas
country: United States
facility: Nicholaos C. Bellos, MD, PA
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Stafford
country: United States
facility: Saint Hope Foundation - Stafford Clinic
state: Texas
city: Curitiba
country: Brazil
facility: Instituto A.Z. de Pesquisa e Ensino
state: PR
city: Nova Iguacu
country: Brazil
facility: Hospital Geral de Nova Iguacu
state: RJ
city: PoA
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: RS
city: Campinas
country: Brazil
facility: Instituto de Infectologia Campinas
state: SP
city: Sao Paulo
country: Brazil
facility: Centro de Referencia e Treinamento DST/AIDS
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Heliopolis
state: SP
city: Koeln
country: Germany
facility: Klinikum der Universitaet zu Koeln, Klinik I fuer Innere Medizin
city: Bologna
country: Italy
facility: Unita' Operativa Malattie Infettive
city: Roma
country: Italy
facility: U.O.S. Immunologia Clinica
city: Kota Bharu
country: Malaysia
facility: Hospital Raja Perempuan Zainab II
state: Kelantan
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Szczecin
country: Poland
facility: Oddzial do Leczenia HIV
city: Warszawa
country: Poland
facility: SPZOZ Wojewodzki Szpital Zakazny
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa - Zona Central - Hospital Santo António Capuchos
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental, EPE.
city: Porto
country: Portugal
facility: Hospital São João
city: Porto
country: Portugal
facility: Hospital de Joaquim Urbano
city: Bayamon
country: Puerto Rico
facility: Innovative Care PSC
city: Ponce
country: Puerto Rico
facility: Ararat Research Center
city: Rio Piedras
country: Puerto Rico
facility: University of Puerto Rico - Medical Sciences Campus - Puerto Rico Medical Center
city: San Juan
country: Puerto Rico
facility: HOPE Clinical Research
city: San Juan
country: Puerto Rico
facility: UPR-CTU Pharmacy
city: Johannesburg
country: South Africa
facility: Soweto Clinical Trials Centre
state: Gauteng
city: Johannesburg
country: South Africa
facility: University of Witwatersrand
state: Gauteng
city: Soweto
country: South Africa
facility: Chris Hani Baragwanath Hospital
state: Johannesburg
city: Dundee
country: South Africa
facility: Dr. J Fourie Medical Centre
state: Kwazulu-natal
city: Durban
country: South Africa
facility: 203 Maxwell Centre
state: Kwazulu-natal
city: Cape Town
country: South Africa
facility: Willowmead Medical Center
state: Western CAPE
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation
state: Western CAPE
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Kaohsiung County
country: Taiwan
facility: Department of Infectious Disease, E-Da Hospital
city: Taipei
country: Taiwan
facility: Veterans General Hospital - Taipei
city: Berezyna
country: Ukraine
facility: Vinnitsa Regional center for AIDS Prevention and Control
state: Vinnitsa District, Vinnitsa Region
city: Donetsk
country: Ukraine
facility: Donetsk Regional Center of AIDSs prophylaxis and control
city: Lugansk
country: Ukraine
facility: Lugansk Regional Center of AIDS prophylaxis and control
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
state: EAST Sussex
city: Crumpsall
country: United Kingdom
facility: North Manchester General Hospital
state: Greater Manchester
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary GUM Clinic
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: