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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00824421
First received: January 15, 2009
Last updated: December 9, 2013
Last verified: November 2011

January 15, 2009
December 9, 2013
February 2009
October 2011   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Percentage of subjects with HIV-1 RNA <48 copies/mL at 48 weeks. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00824421 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA at Week 24 and 96 [ Time Frame: Week 24, 96 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Plasma Concentration of Lersivirine at 24 Hour [ Time Frame: 24 hrs post-dose on Week 4 ] [ Designated as safety issue: No ]
    The observed plasma concentration at 24 hours post-dose (C 24h).
  • Safety and tolerability as measured by spontaneous adverse event reports, serious adverse events and safety laboratory tests. [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) analyses. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • UK-453,061 PK parameters AUC24, Cmax, and C24 (PK sub-study). [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • The change from baseline in log10 transformed HIV-1 RNA levels at 24, 48, and 96 weeks. [ Time Frame: 24-96 weeks ] [ Designated as safety issue: Yes ]
  • The time-averaged difference (TAD) in log10 transformed HIV-1 RNA levels at 24, 48 and 96 weeks. [ Time Frame: 24-96 weeks ] [ Designated as safety issue: Yes ]
  • The percentage of subjects with virologic response at 48 and 96 weeks. [ Time Frame: 48-96 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in CD4+ count (absolute and percentage) at 24, 48, and 96 weeks. [ Time Frame: 24-96 weeks ] [ Designated as safety issue: Yes ]
  • Genotypic and phenotypic susceptibility at the time of treatment failure. [ Time Frame: TBD ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
HIV-1
  • 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.
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
195
October 2011
October 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Canada,   Italy,   Mexico,   Poland,   South Africa,   Switzerland,   United Kingdom
 
NCT00824421
A5271015
Yes
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
November 2011

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