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 ]

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) ]

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) ]

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 ]

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

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 ]

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) ]

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) ]

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


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