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Trial record 1 of 1 for:    NCT00824421
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A Study Of Different Doses Of UK-453, 061 Plus Truvada Compared To Efavirenz Plus Truvada In Patients Who Have Not Been Previously Treated For HIV-1

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ClinicalTrials.gov Identifier: NCT00824421
Recruitment Status : Completed
First Posted : January 16, 2009
Results First Posted : January 24, 2014
Last Update Posted : January 24, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 15, 2009
First Posted Date  ICMJE January 16, 2009
Results First Submitted Date  ICMJE December 9, 2013
Results First Posted Date  ICMJE January 24, 2014
Last Update Posted Date January 24, 2014
Study Start Date  ICMJE February 2009
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2013)
Percentage of Participants With Less Than 50 Copies Per Milliliter (Copies/mL) of Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) at Week 48 [ Time Frame: Week 48 ]
Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Original Primary Outcome Measures  ICMJE
 (submitted: January 15, 2009)
Percentage of subjects with HIV-1 RNA <48 copies/mL at 48 weeks. [ Time Frame: 48 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2013)
  • Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA at Week 24 and 96 [ Time Frame: Week 24, 96 ]
    Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
  • Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA at Week 24, 48 and 96 [ Time Frame: Week 24, 48, 96 ]
    Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
  • Change From Baseline in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 [ Time Frame: Baseline, Week 24, 48, 96 ]
    For the log 10 scale, all the HIV-1 RNA levels were log 10 transformed prior to the average calculations. Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
  • Time-Averaged Difference (TAD) in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 [ Time Frame: Baseline up to 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 was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
  • Percentage of Participants With Response as Determined Using the Time-to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96 [ Time Frame: Week 24, 48, 96 ]
    TLOVR50 response is 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; met treatment failure [TF] criteria). TF: an increase to at least 3 times 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). TF criteria's defined above were confirmed by second measurement at least 14 days after first. In 'TLOVR50', '50' denotes the lower limit of quantification (LLOQ) of assay (which is 50 copies/mL). Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
  • Change From Baseline in Cluster of Differentiation (CD4+) Absolute Cell Count at Week 24, 48 and 96 [ Time Frame: Baseline, Week 24, 48, 96 ]
    Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
  • Change From Baseline in Cluster of Differentiation (CD4+) Percentage Cell Count at Week 24, 48 and 96 [ Time Frame: Baseline, Week 24, 48, 96 ]
    Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
  • Number of Participants With NRTI and NNRTI Resistance-Associated Mutations (RAMs) at Time of Treatment Failure Through Week 24, 48 and 96 [ Time Frame: Day 1 (pre-dose) through Week 24, 48, 96 ]
    Phenotypic resistance and genotypic resistance was assessed for all participants at Day 1 predose, and was evaluated for nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs) resistance-associated mutations at time of treatment failure using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure, up to Week 96.
  • Number of Participants With Laboratory Test Abnormalities [ Time Frame: Baseline up to Week 96 or early termination ]
    Laboratory analysis included hematology, blood chemistry, serum and urine pregnancy test, hepatitis testing and urinalysis. Laboratory values that met the criteria of the Division of Acquired Immuno Deficiency Syndrome (DAIDS) grade 1 (mild, symptoms causing no or minimal interference with usual social and functional activities) or greater were considered as abnormal.
  • Population Pharmacokinetic (PK) of Lersivirine [ Time Frame: Week 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.
  • Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin) [ Time Frame: Week 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.
  • Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lersivirine [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hours (hrs) post-dose on Week 4 ]
    AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0-24). Only participants from Lersivirine treatment arms were planned to be analyzed for Pharmacokinetic (PK) sub-study.
  • Maximum Observed Plasma Concentration (Cmax) of Lersivirine [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4 ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lersivirine [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4 ]
  • Plasma Concentration of Lersivirine at 24 Hour [ Time Frame: 24 hrs post-dose on Week 4 ]
    The observed plasma concentration at 24 hours post-dose (C 24h).
Original Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2009)
  • Safety and tolerability as measured by spontaneous adverse event reports, serious adverse events and safety laboratory tests. [ Time Frame: 96 weeks ]
  • Pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) analyses. [ Time Frame: 48 weeks ]
  • UK-453,061 PK parameters AUC24, Cmax, and C24 (PK sub-study). [ Time Frame: 4 weeks ]
  • The percentage of subjects with fewer than 48 copies of HIV-1 RNA per milliliter of plasma at 24 and 96 weeks. [ Time Frame: 24-96 weeks ]
  • The percentage of subjects with fewer than 400 copies of HIV-1 RNA per milliliter of plasma at 24, 48, and 96 weeks. [ Time Frame: 24-96 weeks ]
  • The change from baseline in log10 transformed HIV-1 RNA levels at 24, 48, and 96 weeks. [ Time Frame: 24-96 weeks ]
  • The time-averaged difference (TAD) in log10 transformed HIV-1 RNA levels at 24, 48 and 96 weeks. [ Time Frame: 24-96 weeks ]
  • The percentage of subjects with virologic response at 48 and 96 weeks. [ Time Frame: 48-96 weeks ]
  • Change from baseline in CD4+ count (absolute and percentage) at 24, 48, and 96 weeks. [ Time Frame: 24-96 weeks ]
  • Genotypic and phenotypic susceptibility at the time of treatment failure.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Of Different Doses Of UK-453, 061 Plus Truvada Compared To Efavirenz Plus Truvada In Patients Who Have Not Been Previously Treated For HIV-1
Official Title  ICMJE A Phase 2B Multicenter, Randomized, Double-Blind, Comparative Trial Of UK-453,061, In Combination With Tenofovir Df And Emtricitabine Versus Efavirenz In Combination With Tenofovir DF And Emtricitabine For The Treatment Of Antiretroviral-Naive HIV-1 Infected Subjects
Brief Summary This is a 96 week study to determine if UK- 453,061 in combination with Truvada is as efficacious, safe and tolerable as efavirenz in combination with Truvada in HIV-1 infected patients who have not been previously treated with antiretroviral drugs.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE HIV-1
Intervention  ICMJE
  • Drug: UK-453, 061
    UK-453,061 500 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.
  • Drug: UK-453, 061
    UK-453,061 750 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.
  • Drug: EFV +TVA
    Efavirenz 600 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 tablets mg PO QD.
Study Arms  ICMJE
  • Experimental: UK- 453,061 Dose One
    UK 453,061 Dose One plus Truvada
    Intervention: Drug: UK-453, 061
  • Experimental: UK-453,061 Dose Two
    UK 453,061 Dose Two plus Truvada
    Intervention: Drug: UK-453, 061
  • Active Comparator: Efavirenz + Truvada
    Efavirenz + Truvada
    Intervention: Drug: EFV +TVA
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 23, 2011)
195
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2009)
189
Actual Study Completion Date  ICMJE October 2011
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 1,000 copies/mL
  • Negative urine pregnancy test.

Exclusion Criteria:

  • Suspected or documented active, untreated HIV-1 related opportunist 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.
  • Absolute CD4 count <200 cells/mm3.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Canada,   Italy,   Mexico,   Poland,   South Africa,   Switzerland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00824421
Other Study ID Numbers  ICMJE A5271015
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP