A Trial Comparing GSK1349572 50mg Plus Abacavir/Lamivudine Once Daily to Atripla (Also Called The SINGLE Trial)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01263015
First received: December 16, 2010
Last updated: May 29, 2014
Last verified: May 2014
Results First Received: August 15, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus I
Interventions: Drug: Dolutegravir
Drug: Atripla
Drug: Abacavir/Lamivudine
Drug: Abacavir/Lamivudine Placebo
Drug: Dolutegravir placebo
Drug: Atripla placebo

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 844 participants (par.) were randomized (1:1) to one of the two treatment arms. Of these, 833 par. received at least one dose of study medication. Of the 11 par. who were randomized but not treated with investigational product, 7 par. withdrew consent, 3 par. were randomized in error, and 1 par. was lost to follow-up.

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Participant Flow:   Overall Study
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
STARTED     414     419  
Ongoing     363     335  
COMPLETED     0     0  
NOT COMPLETED     414     419  
Adverse Event                 10                 42  
Lack of Efficacy                 14                 13  
Protocol Violation                 7                 7  
Lost to Follow-up                 14                 9  
Withdrawal by Subject                 5                 11  
Physician Decision                 1                 2  
Ongoing                 363                 335  



  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
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.
Total Total of all reporting groups

Baseline Measures
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily     Total  
Number of Participants  
[units: participants]
  414     419     833  
Age  
[units: Years]
Mean ± Standard Deviation
  36.5  ± 10.74     36.4  ± 10.43     36.4  ± 10.58  
Gender  
[units: Participants]
     
Female     67     63     130  
Male     347     356     703  
Race/Ethnicity, Customized  
[units: participants]
     
African American (Af Am)/African Heritage (Af Ht)     98     99     197  
American Indian (AI) or Alaska Native (Nat)     13     17     30  
Asian     9     9     18  
White     284     285     569  
Af Am/Af Ht & AI or Alaska Native     0     1     1  
Af Am/Af Ht & Nat Hawaiian/other Pacific Islander     0     1     1  
Af Am/Af Ht & White     3     2     5  
American Indian or Alaska Native & White     6     4     10  
Asian & White     1     0     1  
Missing     0     1     1  



  Outcome Measures
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1.  Primary:   Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48   [ Time Frame: Week 48 ]

Measure Type Primary
Measure Title Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48
Measure Description The percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 was assessed. Plasma samples were collected for the quantitative assessment of HIV-1 RNA based on the Missing, Switch, or Discontinuation equals Failure (MSDF) algorithm,as codified by the Food and Drug Administration's Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigationl product prior to the visit window) as non-responders, as well as participants who switched their concomitant antiretroviral therapy (ART) in certain scenarios. Since changes in ART were not permitted in this protocol, all such participants who changed ART were to be considered non-responders. Otherwise, virologic success or failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the visit of interest window.
Time Frame Week 48  
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.
Intent-to-Treat-Exposed (ITT-E) Population: all randomized participants who received at least one dose of study medication

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Measured Values
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
Number of Participants Analyzed  
[units: participants]
  414     419  
Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48  
[units: Percentage of participants]
  88     81  


Statistical Analysis 1 for Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Cochran-Mantel-Haenszel
P Value [4] 0.003
Difference in percentage [5] 7.3
95% Confidence Interval ( 2.3 to 12.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority could be concluded if the lower bound of a two-sided 95% confidence interval for the difference (DTG + ABC/3TC minus EFV/TDF/FTC) in percentages between the two treatment arms was > -10%.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value is for the test of superiority.
[5] Other relevant estimation information:
  The estimated value reflects the percentage on DTG + ABC/3TC minus the percentage on EFV/TDF/FTC, based on Cochran-Mantel Haenszel stratified analysis adjusting for the following Baseline stratification factors: HIV-1 RNA and CD4+ cell count.



2.  Secondary:   Time to Viral Suppression (<50 c/mL)   [ Time Frame: From Baseline until data cut off for Week 48 analysis (average of 357.0 days for DTG; average of 332.2 study days for EFV/TDF/FTC) ]

Measure Type Secondary
Measure Title Time to Viral Suppression (<50 c/mL)
Measure Description Viral suppression is defined as the first viral load value<50 c/mL. The Kaplan-Meier method was used to estimate time to viral suppression, defined as the time from the first dose of study treatment until the first viral load value <50 c/mL was reached. Participants who withdrew for any reason without having suppressed prior to the analysis were censored.
Time Frame From Baseline until data cut off for Week 48 analysis (average of 357.0 days for DTG; average of 332.2 study days for EFV/TDF/FTC)  
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

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Measured Values
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
Number of Participants Analyzed  
[units: participants]
  414     419  
Time to Viral Suppression (<50 c/mL)  
[units: days]
Median ( 95% Confidence Interval )
  28  
  ( 28.0 to 29.0 )  
  84  
  ( 83.0 to 84.0 )  

No statistical analysis provided for Time to Viral Suppression (<50 c/mL)



3.  Secondary:   Number of Participants With a Confirmed Plasma HIV-1 RNA Level >=1000 c/mL at or After Week 16 and Before Week 24, or a Confirmed Plasma HIV-1 RNA Level >=200 c/mL at or After Week 24   [ Time Frame: From Baseline until data cut off for the Week 48 analysis (average of 357.0 study days for DTG; average of 332.2 study days for EFV/TDF/FTC) ]

Measure Type Secondary
Measure Title Number of Participants With a Confirmed Plasma HIV-1 RNA Level >=1000 c/mL at or After Week 16 and Before Week 24, or a Confirmed Plasma HIV-1 RNA Level >=200 c/mL at or After Week 24
Measure Description Data are presented as Kaplan Meier estimates of virologic failure (VF), defined as a confirmed plasma HIV-1 RNA level >=1000 c/mL at or after Week 16 and before Week 24, or a confirmed plasma HIV-1 RNA level >=200 c/mL at or after Week 24. A plasma HIV-1 RNA value was considered to be confirmed failure if a consecutive measurement satisfied the same failure criterion. The number of participants who experienced autoimmune deficiency syndrome (AIDS) Clinical Trials Group (ACTG) VFs was measured. For participants who withdrew from the study/were not documented to have reached confirmed VF at the cut off date of the Week 48 analysis, time to VF was to be censored at the planned visit week of the last measured plasma HIV-1 RNA sample. Data for participants who missed three consecutive scheduled plasma HIV-1 RNA measurements were to be censored at the planned visit week of the last assessment prior to the 3 consecutive missed visits.
Time Frame From Baseline until data cut off for the Week 48 analysis (average of 357.0 study days for DTG; average of 332.2 study days for EFV/TDF/FTC)  
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

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Measured Values
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
Number of Participants Analyzed  
[units: participants]
  414     419  
Number of Participants With a Confirmed Plasma HIV-1 RNA Level >=1000 c/mL at or After Week 16 and Before Week 24, or a Confirmed Plasma HIV-1 RNA Level >=200 c/mL at or After Week 24  
[units: participants]
   
ACTG virologic failures     2     6  
Censored participants     412     413  

No statistical analysis provided for Number of Participants With a Confirmed Plasma HIV-1 RNA Level >=1000 c/mL at or After Week 16 and Before Week 24, or a Confirmed Plasma HIV-1 RNA Level >=200 c/mL at or After Week 24



4.  Secondary:   Change From Baseline in Plasma HIV-1 RNA at Weeks 4, 8, 12, 24, 32, and 48   [ Time Frame: Baseline and Weeks 4, 8, 12, 24, 32, and 48 ]

Measure Type Secondary
Measure Title Change From Baseline in Plasma HIV-1 RNA at Weeks 4, 8, 12, 24, 32, and 48
Measure Description Blood samples were collected for the measurement of HIV-1 RNA in plasma. Changes from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline and Weeks 4, 8, 12, 24, 32, and 48  
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. Only those participants available at the indicated time points were assessed.

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Measured Values
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
Number of Participants Analyzed  
[units: participants]
  414     419  
Change From Baseline in Plasma HIV-1 RNA at Weeks 4, 8, 12, 24, 32, and 48  
[units: log10 copies/mL]
Mean ± Standard Deviation
   
Week 4, n=404, 391     -2.88  ± 0.58     -2.25  ± 0.52  
Week 8, n=395, 386     -2.99  ± 0.64     -2.60  ± 0.60  
Week 12, n=394, 377     -3.01  ± 0.70     -2.85  ± 0.63  
Week 24, n=389, 364     -3.05  ± 0.69     -3.01  ± 0.76  
Week 32, n=380, 355     -3.04  ± 0.70     -3.05  ± 0.72  
Week 48, n=370, 343     -3.03  ± 0.69     -3.04  ± 0.69  

No statistical analysis provided for Change From Baseline in Plasma HIV-1 RNA at Weeks 4, 8, 12, 24, 32, and 48



5.  Secondary:   Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Week 48   [ Time Frame: Baseline and Week 48 ]

Measure Type Secondary
Measure Title Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Week 48
Measure Description CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immunocompromise. The CD4 count is used to stage the patient's disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start antiretroviral therapy. Change from Baseline was calculated as the Week 48 value minus the Baseline value. The least squares mean is the estimated mean change from Baseline in CD4+ cell counts at Week 48 calculated from a repeated measures model including the following covariates: treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, treatment*visit interaction, Baseline HIV-1 RNA*visit interaction, and Baseline CD4+ cell count*visit interaction. No assumptions were made about the correlations between a participant's readings of CD4+, i.e., the correlation matrix for within-participant errors is unstructured.
Time Frame Baseline and Week 48  
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

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Measured Values
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
Number of Participants Analyzed  
[units: participants]
  414     419  
Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Week 48  
[units: cells per millimeters cubed (cells/mm^3)]
Least Squares Mean ± Standard Error
  267.06  ± 9.054     208.16  ± 9.314  

No statistical analysis provided for Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Week 48



6.  Secondary:   Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences   [ Time Frame: From Baseline until Week 48 ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences
Measure Description Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline (BS) to a CDC CAT C event (EV); CDC CAT B at BS to a CDC CAT C EV; CDC CAT C at BS to a new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.
Time Frame From Baseline until Week 48  
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

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Measured Values
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
Number of Participants Analyzed  
[units: participants]
  414     419  
Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences  
[units: participants]
   
Any category condition     11     14  
Any Category B condition     6     8  
Any Category C condition     5     5  
Any death     0     2  
Progression from CAT A to CAT C     4     2  
Progression from CAT C to new CAT C     1     2  
Progression from CAT A, B, or C to death     0     2  

No statistical analysis provided for Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences



7.  Secondary:   Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities   [ Time Frame: From Baseline until data cut off for the Week 48 analysis (average of 357.0 study days for DTG; average of 332.2 study days for EFV/TDF/FTC) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities
Measure Description All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), asparate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol calculation, lipase, phosphorus inorganic, total bilirubin, and triglycerides. All Grade 1 to 4 post-Baseline-emergent hematology toxities included hemoglobin, platelet count, total neutrophils, and white blood cell count. The Division of AIDS (DAIDS) defined toxicity grades as follows: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening; Grade 5, death.
Time Frame From Baseline until data cut off for the Week 48 analysis (average of 357.0 study days for DTG; average of 332.2 study days for EFV/TDF/FTC)  
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.
Safety Population: all participants who received at least one dose of investigational product

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Measured Values
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
Number of Participants Analyzed  
[units: participants]
  414     419  
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities  
[units: participants]
   
ALT     42     67  
Albumin     0     1  
ALP     8     42  
AST     50     63  
CO2 content/bicarbonate     89     80  
Cholesterol     112     110  
CK     57     51  
Creatinine     11     4  
Hyperglycaemia     91     72  
Hyperkalemia     3     7  
Hypernatremia     7     7  
Hypoglycaemia     17     15  
Hypokalemia     22     16  
Hyponatremia     54     72  
LDL cholesterol calculation     88     75  
Lipase     87     81  
Phosphorus, inorganic     70     96  
Total bilirubin     17     3  
Triglycerides     8     9  
Hemoglobin     5     6  
Platelet count     11     13  
Total neutrophils     57     63  
White Blood Cell count     7     16  

No statistical analysis provided for Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities



8.  Secondary:   Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF)   [ Time Frame: Baseline to the time of virological failure (up to Week 48) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF)
Measure Description Whole blood samples were collected from participants to provide plasma for storage samples for potential viral genotypic and phenotypic analyses. Participants with confirmed virological failure (confirmed HIV-1 RNA >=50 copies/mL throughout the study and/or confirmed HIV-1 RNA >=200 copies/mL at Week 48) had plasma samples tested for HIV-1 RT genotype and HIV-1 integrase genotype from Baseline samples and from samples collected at the time of virological failure. Genotype testing was conducted at Day 1 and at the time of suspected protocol-defined virological failure (PDVF). A genotyping assessment was made of change across all amino acids within the integrase (IN)-encoding region, with particular attention paid to specific amino acid changes associated with the development of resistance to RAL, ELV, or DTG.
Time Frame Baseline to the time of virological failure (up to Week 48)  
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.
PDVF Genotypic Population: all participants in the ITT-E Population with available on-treatment genotypic resistance data at the time of PDVF

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Measured Values
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
Number of Participants Analyzed  
[units: participants]
  18     17  
Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF)  
[units: participants]
   
IN substitution E157Q/P     1     0  
RT mutation K65K/R     0     1  
RT mutation K101E     0     1  
RT mutation K103K/N     0     1  
RT mutation K103N     0     1  
RT mutation G190G/A     0     2  
PI mutation     0     0  

No statistical analysis provided for Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF)



9.  Secondary:   Change From Baseline in the Symptom Bother Score (SBS) at Week 4   [ Time Frame: Baseline and Week 4 ]

Measure Type Secondary
Measure Title Change From Baseline in the Symptom Bother Score (SBS) at Week 4
Measure Description The Symptom Distress Module (SDM) is a 20-item, self-reported questionnaire measuring the presence/perceived distress linked to symptoms associated with HIV/its treatments. Developed with support from the AIDS Clinical Trials Group of the U.S. National Institute of Allergy and Infectious Diseases, it has demonstrated construct validity and has shown strong associations with physical/mental health summary scores and with disease severity. The SDM consists of 2 main scores: symptom count and the SBS, ranging from 0 (best) to 80 (worst) and based on the degree of bother that each symptom present posed. The SBS was calculated by adding the 20 individual bother item scores, which were calculated as: 0, “I do not have this symptom”; 1, "It doesn’t bother me”; 2, “It bothers me a little”; 3, “It bothers me”; 4, "It bothers me a lot." Estimates are calculated from an analysis of covariance (ANCOVA) model adjusting for age, sex, race, Baseline (BL) viral load, BL CD4+ cell count, and BL SBS.
Time Frame Baseline and Week 4  
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. Participants with missing bother item scores at Week 4 had their last observation carried forward (LOCF). Only those participants contributing to the model (i.e., without missing response variables after LOCF or covariates) were analyzed.

Reporting Groups
  Description
DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily Participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg.
EFV/TDF/FTC 600/200/300 mg Once Daily Participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg.

Measured Values
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily     EFV/TDF/FTC 600/200/300 mg Once Daily  
Number of Participants Analyzed  
[units: participants]
  394     393  
Change From Baseline in the Symptom Bother Score (SBS) at Week 4  
[units: scores on a scale]
Least Squares Mean ± Standard Error
  -1.818  ± 0.3849     -1.246  ± 0.3854  

No statistical analysis provided for Change From Baseline in the Symptom Bother Score (SBS) at Week 4




  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
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:
Brinson C, Walmsley S, Arasteh K, et al. Dolutegravir treatment response and safety by key subgroups in treatment naive HIV-infected individuals. Published at: Conference on Retroviruses and Opportunistic Infections - 20th Annual; March 3-6, 2013; Atlanta, GA.


Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01263015     History of Changes
Other Study ID Numbers: 114467
Study First Received: December 16, 2010
Results First Received: August 15, 2013
Last Updated: May 29, 2014
Health Authority: Spain: Agencia Espanola de Medicamentos y Productos Sanitarios
Italy: Comitato Etico Fondazione Centro San Raffaele del Monte Tabor - Via Olgettina, 60 - 20132 Milano
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Belgium: Federal Agency for Medicines and Health Products, FAMHP
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Hungary: Országos Gyógyszerészeti Intézet
South Africa: Medicines Control Council
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Romania: National Medicines Agency
Denmark: Danish Medicines Agency
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Canada: Health Canada
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Australia: Therapeutic Goods Administration