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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: July 28, 2016
Last verified: June 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  
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
  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 ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title Proportion of Subjects Responding Based on Plasma HIV-1 RNA <50 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 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  
Number of Participants Analyzed  
[units: participants]
  414     419  
Proportion of Subjects Responding Based on Plasma HIV-1 RNA <50 c/mL at Week 48  
[units: Percentage of participants]
  88     81  


Statistical Analysis 1 for Proportion of Subjects Responding Based on Plasma HIV-1 RNA <50 c/mL at Week 48
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Wilcoxon (Mann-Whitney)
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.



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 ]

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: July 28, 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