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

This study has been completed.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01263015
First received: December 16, 2010
Last updated: September 23, 2016
Last verified: September 2016
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
Study consisted of 96 weeks double-blind phase, followed by a 48 week open-label phase.

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 During double-blind phase, 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 for 96 weeks.
EFV/TDF/FTC 600/200/300 mg Once Daily During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks.

Participant Flow for 2 periods

Period 1:   Double-blind Phase: 96 Weeks Duration
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily   EFV/TDF/FTC 600/200/300 mg Once Daily
STARTED   414   419 
COMPLETED   342   310 
NOT COMPLETED   72   109 
Adverse Event                13                48 
Lack of Efficacy                18                14 
Protocol Violation                14                12 
Lost to Follow-up                17                18 
Withdrawal by Subject                9                15 
Physician Decision                1                2 

Period 2:   Open-label Phase: 48 Weeks Duration
    DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily   EFV/TDF/FTC 600/200/300 mg Once Daily
STARTED   341   309 
COMPLETED   317   278 
NOT COMPLETED   24   31 
Adverse Event                3                10 
Lack of Efficacy                7                2 
Protocol Violation                3                2 
Lost to Follow-up                8                8 
Physician Decision                0                2 
Withdrawal by Subject                3                7 



  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 During double-blind phase, 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 for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.
EFV/TDF/FTC 600/200/300 mg Once Daily During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
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 
Overall Participants Analyzed 
[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
  Show All Outcome Measures

1.  Primary:   Proportion of Subjects Responding Based on Plasma HIV-1 RNA <50 c/mL at Week 48   [ Time Frame: Week 48 ]

2.  Secondary:   Time to Viral Suppression (<50 c/mL)   [ Time Frame: From Baseline until Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC) ]

3.  Secondary:   Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 96 and Week 144   [ Time Frame: Week 96 and Week 144 ]

4.  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 Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC) ]

5.  Secondary:   Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144   [ Time Frame: Baseline and at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 ]

6.  Secondary:   Change From Baseline in CD4+ Cell Counts at Week 144   [ Time Frame: Baseline and Week 144 ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Change From Baseline in CD4+ Cell Counts at Week 144
Measure Description Cluster of differentiation (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 144 value minus the Baseline value. The least squares mean is the estimated mean change from Baseline in CD4+ cell counts at Week 144 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 144  
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 During double-blind phase, 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 for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.
EFV/TDF/FTC 600/200/300 mg Once Daily During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.

Measured Values
   DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily   EFV/TDF/FTC 600/200/300 mg Once Daily 
Participants Analyzed 
[Units: Participants]
 414   419 
Change From Baseline in CD4+ Cell Counts at Week 144 
[Units: Cells per millimeters cubed (cells/mm^3)]
Least Squares Mean (Standard Deviation)
 378.48  (10.99)   331.57  (11.59) 


Statistical Analysis 1 for Change From Baseline in CD4+ Cell Counts at Week 144
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Repeated Measure Mixed Model
P Value [4] 0.003
[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:
  Adjusted mean is the estimated mean change from baseline (BL) in CD4 + Cell Count at Week 144 in each arm calculated from a repeated measures model including the following covariates: treatment, visit, BL plasma HIV-1 RNA, BL CD4 cell count, treatment*visit interaction, BL HIV-1 RNA*visit interaction and BL CD4 cell count*visit interaction. No assumptions were made about the correlations between a par.’s readings of CD4 i.e. the correlation matrix for within-subject errors is unstructured.
[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.



7.  Secondary:   Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144   [ Time Frame: Baseline and Week 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 ]

8.  Secondary:   Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144   [ Time Frame: From Baseline until Week 144 ]

9.  Secondary:   Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144   [ Time Frame: From Baseline until Week 144 ]

10.  Secondary:   Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF) Through 144   [ Time Frame: Through Week 144 ]

11.  Secondary:   Change From Baseline in the Symptom Bother Score (SBS) at Week 4 Through Week 48   [ Time Frame: Baseline and Week 4 through 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
No text entered.


  More Information
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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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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: September 23, 2016
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 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
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Australia: Therapeutic Goods Administration