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

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, 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.
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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)
Sex: Female, Male; [Units: Participants]; Count of Participants
Female	67 16.2%	63 15.0%	130 15.6%
Male	347 83.8%	356 85.0%	703 84.4%
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:

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

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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) ]

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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 ]

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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) ]

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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 ]

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6. Secondary:

Change From Baseline in CD4+ Cell Counts at Week 144 [ Time Frame: Baseline and Week 144 ]

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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 ]

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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 ]

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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 ]

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Measure Type	Secondary
Measure Title	Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144
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 Week 144

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	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
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144; [Units: Participants]
Week 144, ALT	62	81
Week 144, Albumin	0	1
Week 144, ALP	17	53
Week 144, AST	77	85
Week 144, CO2 content/bicarbonate	135	134
Week 144, Cholesterol	156	140
Week 144, CK	91	79
Week 144, Creatinine	17	6
Week 144, Hyperglycaemia	121	105
Week 144, Hyperkalemia	4	12
Week 144, Hypernatremia	11	9
Week 144, Hypoglycaemia	24	21
Week 144, Hypokalemia	38	21
Week 144, Hyponatremia	63	86
Week 144, LDL cholesterol calculation	124	111
Week 144, Lipase	111	110
Week 144, Phosphorus, inorganic	109	134
Week 144, Total bilirubin	22	4
Week 144, Triglycerides	11	11
Week 144, Hemoglobin	7	11
Week 144, Platelet count	20	19
Week 144, Total neutrophils	70	80
Week 144, White Blood Cell count	9	18

No statistical analysis provided for Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144

10. Secondary:

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

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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 ]

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  Serious Adverse Events

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  Other Adverse Events

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  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: 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. 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. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

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):

Walmsley S, Baumgarten A, Berenguer J, Felizarta F, Florence E, Khuong-Josses MA, Kilby JM, Lutz T, Podzamczer D, Portilla J, Roth N, Wong D, Granier C, Wynne B, Pappa K. Brief Report: Dolutegravir Plus Abacavir/Lamivudine for the Treatment of HIV-1 Infection in Antiretroviral Therapy-Naive Patients: Week 96 and Week 144 Results From the SINGLE Randomized Clinical Trial. J Acquir Immune Defic Syndr. 2015 Dec 15;70(5):515-9. doi: 10.1097/QAI.0000000000000790. Erratum in: J Acquir Immune Defic Syndr. 2016 Jan 1;71(1):e33.

Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutiérrez F, Hocqueloux L, Maggiolo F, Sandkovsky U, Granier C, Pappa K, Wynne B, Min S, Nichols G; SINGLE Investigators. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013 Nov 7;369(19):1807-18. doi: 10.1056/NEJMoa1215541.

Responsible Party:	ViiV Healthcare
ClinicalTrials.gov Identifier:	NCT01263015 History of Changes
Other Study ID Numbers:	114467
First Submitted:	December 16, 2010
First Posted:	December 20, 2010
Results First Submitted:	August 15, 2013
Results First Posted:	July 2, 2014
Last Update Posted:	April 4, 2018