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
  Purpose

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.


Condition Intervention Phase
HIV-1
Drug: UK-453, 061
Drug: EFV +TVA
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Enrollment: 195
Study Start Date: February 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: UK- 453,061 Dose One
UK 453,061 Dose One plus Truvada
Drug: UK-453, 061
UK-453,061 500 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.
Experimental: UK-453,061 Dose Two
UK 453,061 Dose Two plus Truvada
Drug: UK-453, 061
UK-453,061 750 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 mg tablets PO QD.
Active Comparator: Efavirenz + Truvada
Efavirenz + Truvada
Drug: EFV +TVA
Efavirenz 600 mg tablets PO QD + Tenofovir DF 300 mg/Emtricitabine 200 tablets mg PO QD.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00824421

  Show 31 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00824421     History of Changes
Other Study ID Numbers: A5271015
Study First Received: January 15, 2009
Results First Received: December 9, 2013
Last Updated: December 9, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Pfizer:
HIV-1. Treatment Naive
HIV Infections
treatment naive

Additional relevant MeSH terms:
Efavirenz
Tenofovir
Tenofovir disoproxil
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 29, 2014