A Simplification Study of Unboosted Reyataz With Epzicom (ASSURE)

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01102972
First received: April 8, 2010
Last updated: October 24, 2013
Last verified: September 2013
Results First Received: November 28, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus
Interventions: Drug: Reyataz + Norvir + Truvada
Drug: Reyataz + Epzicom

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants (PAR) were recruited from 44 centers in the United States, including Puerto Rico. ATV, atazanavir; RTV, ritonavir; TDF, tenofovir; FTC, emtricitrabine; QD, once daily; HIV-RNA, human immunodeficiency virus-ribonucleic acid; c, copies; ml, milliliters; ART, antiretroviral; mg, milligrams, ABC/3TC, abacavir sulfate/lamivudine.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
HLA-B*5701-negative PAR receiving an ATV/RTV + TDF/FTC regimen QD who are virologically suppressed (plasma HIV-1 RNA <75 c/mL) and met all eligibility requirements were randomized 2:1 to receive an ART regimen of ATV 400 mg QD + ABC/3TC 600 mg/300 mg QD (simplification arm) or ATV/RTV 300 mg/100 mg QD + TDF/FTC 300 mg/200 mg QD (continuation arm).

Reporting Groups
  Description
ABC/3TC + ATV Abacavir (ABC) 600 milligrams (mg)/lamivudine (3TC) 300 mg fixed-dose combination tablet (FDC) once a day (QD) plus atazanavir (ATV) 400 mg (given as oral capsules) QD for 48 weeks
TDF/FTC + ATV/RTV Tenofovir (TDF) 300 mg/Emtricitabine (FTC) 200 mg FDC tablet QD plus Atazanavir (ATV) 300 mg (given as oral capsules)/Ritonavir (RTV) 100 mg (given as oral capsules) QD for 48 weeks

Participant Flow:   Overall Study
    ABC/3TC + ATV     TDF/FTC + ATV/RTV  
STARTED     199 [1]   97 [1]
Completed Week 24     180     88  
COMPLETED     170 [2]   83 [2]
NOT COMPLETED     29     14  
Adverse Event                 8                 2  
Lack of Efficacy                 2                 1  
Protocol Violation                 1                 0  
Lost to Follow-up                 10                 5  
Investigator Discretion                 2                 0  
Withdrawal by Subject                 6                 6  
[1] 297 PAR enrolled. 1 PAR withdrew before taking investigational product and didn’t “start” the study.
[2] These participants completed Study Week 48.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
ABC/3TC + ATV Abacavir (ABC) 600 milligrams (mg)/lamivudine (3TC) 300 mg fixed-dose combination tablet (FDC) once a day (QD) plus atazanavir (ATV) 400 mg (given as oral capsules) QD for 48 weeks
TDF/FTC + ATV/RTV Tenofovir (TDF) 300 mg/Emtricitabine (FTC) 200 mg FDC tablet QD plus Atazanavir (ATV) 300 mg (given as oral capsules)/Ritonavir (RTV) 100 mg (given as oral capsules) QD for 48 weeks
Total Total of all reporting groups

Baseline Measures
    ABC/3TC + ATV     TDF/FTC + ATV/RTV     Total  
Number of Participants  
[units: participants]
  199     97     296  
Age  
[units: Years]
Mean ± Standard Deviation
  42.8  ± 9.54     42.3  ± 10.20     42.6  ± 9.74  
Gender  
[units: Participants]
     
Female     44     18     62  
Male     155     79     234  
Ethnicity (NIH/OMB)  
[units: Participants]
     
Hispanic or Latino     51     26     77  
Not Hispanic or Latino     148     71     219  
Unknown or Not Reported     0     0     0  
Race/Ethnicity, Customized  
[units: Participants]
     
African American/African Heritage     65     37     102  
American Indian or Alaskan Native     3     0     3  
Asian - East Asian Heritage     2     0     2  
Asian - South East Asian Heritage     4     1     5  
Native Hawaiian or Other Pacific Islander     0     1     1  
White - Arabic/North African Heritage     2     0     2  
White - White/Caucasian/European Heritage     120     55     175  
Mixed Race     3     3     6  
Number of participants with the indicated baseline HIV-RNA level [1]
[units: participants]
     
HIV-1 RNA <50     192     93     285  
HIV-1 RNA 50-<75     2     2     4  
HIV-1 RNA >=75     5     2     7  
Number of participants with the indicated Baseline CD4+ Cell Count [2]
[units: participants]
     
CD4+ cells <50     0     0     0  
CD4+ cells 50-<200     14     6     20  
CD4+ cells >=200     185     91     276  
Number of participants with the indicated Center for Disease Control (CDC) Classification [3]
[units: participants]
     
Class A: Asymptomatic/lymphadenopathy/acute HIV     136     67     203  
Class B: Symptomatic, not AIDS     26     13     39  
Class C: AIDS indicator conditions     37     17     54  
Median Baseline CD4+ Cell Count  
[units: cells per cubic millimeter]
Median ( Full Range )
  492.0  
  ( 77.0 to 1196.0 )  
  480.0  
  ( 108.0 to 1479.0 )  
  491.5  
  ( 77.0 to 1479.0 )  
Median Baseline HIV-1 RNA Level  
[units: log10 copies/mL]
Median ( Full Range )
  1.591  
  ( 1.591 to 3.900 )  
  1.591  
  ( 1.591 to 3.285 )  
  1.591  
  ( 1.591 to 3.900 )  
Number of participants with the indicated Baseline Hepatitis B (HB) Status [4]
[units: participants]
     
Reactive     0     0     0  
Non-reactive     199     97     296  
Number of participants with the indicated Baseline Hepatitis C (HC) Status [5]
[units: participants]
     
Reactive     18     8     26  
Non-reactive     181     89     270  
[1] HIV-1 RNA, Human Immunodeficiency Virus type 1 Ribonucleic acid. HIV-1 viral load was measured as virus copies per milliliter (mL) at baseline.
[2] A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts, measured as the number of cells per cubic millimeter.
[3] Acquired Immunodeficiency Syndrome (AIDS) CDC classifications are Asymptomatic, Symptomatic, or AIDS. The CDC categorization of HIV/AIDS is based on the lowest documented CD4 cell count (Class A, >=500 cells per microliter [µl]; Class B, 200-499 cells/µl; Class C, <200 cells/µl) and on previously diagnosed HIV-related conditions.
[4] The HB surface antigen is a protein present on the surface of the hepatitis B virus (HBV). It can be detected in the blood of participants with acute and chronic HBV infections. A non-reactive test result likely means that participants are not infected with HB, but does not exclude the possibility of exposure to or infection with HB.
[5] The HC surface antigen is a protein present on the surface of the hepatitis C virus (HCV). It can be detected in the blood of participants with acute and chronic HCV infections. A non-reactive test result likely means that participants are not infected with HC, but does not exclude the possibility of exposure to or infection with HC.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c)/Milliliter (mL) at the Week 24 Visit: TLOVR Analysis   [ Time Frame: Week 24 ]

2.  Secondary:   Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 c/mL at the Week 24 Visit: Observed, M/D=F, and SNAPSHOT Analyses   [ Time Frame: Week 24 ]

3.  Secondary:   Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 c/mL at the Week 48 Visit: TLOVR, Observed, M/D=F, and SNAPSHOT Analyses   [ Time Frame: Week 48 ]

4.  Secondary:   Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: TLOVR Analysis   [ Time Frame: Week 24 ]

5.  Secondary:   Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: TLOVR Analysis   [ Time Frame: Week 48 ]

6.  Secondary:   Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 24 Visit: Observed, MD=F, and SNAPSHOT Analyses   [ Time Frame: Week 24 ]

7.  Secondary:   Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <400 c/mL at the Week 48 Visit: Observed, MD=F, and SNAPSHOT Analyses   [ Time Frame: Week 48 ]

8.  Secondary:   Change From Baseline in HIV-1 RNA at Week 24   [ Time Frame: Baseline and Week 24 ]

9.  Secondary:   Change From Baseline in HIV-1 RNA at Week 48   [ Time Frame: Baseline and Week 48 ]

10.  Secondary:   Change From Baseline in CD4+ Cell Count at Week 24   [ Time Frame: Baseline and Week 24 ]
  Hide Outcome Measure 10

Measure Type Secondary
Measure Title Change From Baseline in CD4+ Cell Count at Week 24
Measure Description Blood was drawn to analyze for CD4+ cell count. A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts. Change from Baseline was calculated as the Week 24 value minus the Baseline value.
Time Frame Baseline and Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population. Observed Population. Participants withdrew as the study progressed; participants could only be included in the analysis if they had completed a Week 24 visit and had a CD4+ cell count obtained during that visit period.

Reporting Groups
  Description
ABC/3TC + ATV Abacavir (ABC) 600 milligrams (mg)/lamivudine (3TC) 300 mg fixed-dose combination tablet (FDC) once a day (QD) plus atazanavir (ATV) 400 mg (given as oral capsules) QD for 48 weeks
TDF/FTC + ATV/RTV Tenofovir (TDF) 300 mg/Emtricitabine (FTC) 200 mg FDC tablet QD plus Atazanavir (ATV) 300 mg (given as oral capsules)/Ritonavir (RTV) 100 mg (given as oral capsules) QD for 48 weeks

Measured Values
    ABC/3TC + ATV     TDF/FTC + ATV/RTV  
Number of Participants Analyzed  
[units: participants]
  181     89  
Change From Baseline in CD4+ Cell Count at Week 24  
[units: cells per cubic millimeter (mm^3)]
Mean ± Standard Deviation
  47.7  ± 134.02     8.3  ± 122.40  

No statistical analysis provided for Change From Baseline in CD4+ Cell Count at Week 24



11.  Secondary:   Change From Baseline in CD4+ Cell Count at Week 48   [ Time Frame: Baseline and Week 48 ]

12.  Secondary:   Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 24   [ Time Frame: Baseline and Week 24 ]

13.  Secondary:   Change From Baseline in Cholesterol/HDL Ratio at Week 24   [ Time Frame: Baseline and Week 24 ]

14.  Secondary:   Change From Baseline in Fasting Triglycerides, Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, and Low-density Lipoprotein (LDL) Cholesterol at Week 48   [ Time Frame: Baseline and Week 48 ]

15.  Secondary:   Change From Baseline in Cholesterol/HDL Ratio at Week 48   [ Time Frame: Baseline and Week 48 ]

16.  Secondary:   Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 24   [ Time Frame: From Baseline to Week 24 ]

17.  Secondary:   Number of Participants Who Met the Protocol-defined Confirmed Viral Failure Criteria Through Week 48   [ Time Frame: From Baseline to Week 48 ]

18.  Secondary:   Number of Participants Who Experienced Death and/or Disease Progression   [ Time Frame: From Baseline to Week 48 ]

19.  Secondary:   Number of Confirmed Virologic Failure (VF) Participants (PAR) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 24   [ Time Frame: From Baseline to Week 24 ]

20.  Secondary:   Number of Confirmed Virologic Failure (VF) Participants (PAR) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 48   [ Time Frame: From Baseline to Week 48 ]

21.  Secondary:   Number of Confirmed Virologic Failure Participants (PAR) From Baseline Through Week 24 With the Indicated Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Tenofovir, Emtricitabine, Atazanavir, or Ritonavir   [ Time Frame: From Baseline to Week 24 ]

22.  Secondary:   Number of Confirmed Virologic Failure Participants (PAR) From Baseline Through Week 48 With the Indicated Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Tenofovir, Emtricitabine, Atazanavir, or Ritonavir   [ Time Frame: From Baseline to Week 48 ]

23.  Secondary:   Number of Participants With the Indicated Grade 2 to Grade 4 Adverse Events (AEs) Occurring at a Frequency of >=3% in Either Treatment Group   [ Time Frame: From Baseline to Week 24 ]

24.  Secondary:   Number of Participants With the Indicated Grade 2 to Grade 4 Adverse Events (AEs) Occurring at a Frequency of >=3% in Either Treatment Group   [ Time Frame: From Baseline to Week 48 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
This study consists of a 35-day Screening Period, a 48-week Treatment Period, and a Follow-up Period (contact ~2-4 weeks after the Week 48/Withdrawal Visit). Data from Week 24 (primary endpoint) and Week 48 (final data) are presented in this summary.


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