A Study of GSK1349572 Versus Raltegravir (RAL) With Investigator Selected Background Regimen in Antiretroviral-Experienced, Integrase Inhibitor-Naive Adults (SAILING)

This study is ongoing, but not recruiting participants.

Sponsor:

Collaborators:

Shionogi

GlaxoSmithKline

Information provided by (Responsible Party):

ViiV Healthcare

ClinicalTrials.gov Identifier:

NCT01231516

First received: October 21, 2010

Last updated: March 20, 2014

Last verified: March 2014

History of Changes

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
Interventions:	Drug: GSK1349572 Drug: Raltegravir Drug: GSK1349572 Placebo Drug: Raltegravir 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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1441 participants were screened; 724 were randomized. A total of 719 participants received at least 1 dose of study medication and comprised the intent-to-treat exposed (ITT-E) population. Four participants from one closed site were removed from the ITT-E population creating the modified ITT-E population with 715 participants.

Reporting Groups

Description

DTG 50 mg OD

Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continue to have access to DTG in the Open-Label phase of the study.

RAL 400 mg BID

Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GSK will continue to supply RAL in the Open-Label Phase until it is commercially available.

Participant Flow for 2 periods

Period 1: 48 Week Double-blind Phase

	DTG 50 mg OD	RAL 400 mg BID
STARTED	357	362
COMPLETED	299	283
NOT COMPLETED	58	79
Adverse Event	4	11
Lack of Efficacy	20	42
Protocol Violation	9	6
Met Protocol-Defined Stopping Criteria	5	3
Lost to Follow-up	5	10
Physician Decision	1	1
Withdrawal by Subject	11	5
Site Closed	3	1

Period 2: Open-label Phase

	DTG 50 mg OD	RAL 400 mg BID
STARTED	295 ^[1]	27 ^[2]
Ongoing at the Time of Analysis	282	23
COMPLETED	0	1
NOT COMPLETED	295	26
Lack of Efficacy	7	3
Protocol Violation	2	0
Lost to Follow-up	3	0
Withdrawal by Subject	1	0
Ongoing at the time of analysis	282	23

[1]	4 participants completed the Double-blind Phase but did not enter the Open-label Phase.
[2]	256 participants completed the Double-blind Phase but did not enter the Open-label Phase.

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 OD	Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) + matching Raltegravir (RAL) placebo twice daily (BID), one in the morning (AM dose) and one in the evening (PM dose) + investigator selected background antiretroviral (ART) therapy for 48 weeks. Participants who successfully completed 48 weeks of treatment continue to have access to DTG in the Open-Label phase of the study.
RAL 400 mg BID	Participants received matching DTG placebo OD + RAL 400 mg BID as AM and PM doses + investigator selected background ART therapy for 48 weeks. Participants were discontinued from the study after completion of the Week 48 visit unless a participant successfully completed Week 48 and RAL was not approved and commercially available within the country, GSK will continue to supply RAL in the Open-Label Phase until it is commercially available.
Total	Total of all reporting groups

Baseline Measures

	DTG 50 mg OD	RAL 400 mg BID	Total
Number of Participants [units: participants]	354	361	715
Age ^[1] [units: Years] Mean ± Standard Deviation	42.6 ± 10.45	42.5 ± 9.81	42.5 ± 10.13
Gender ^[1] [units: Participants]
Female	107	123	230
Male	247	238	485
Race/Ethnicity, Customized ^[1] [units: Participants]
African American/African Heritage	143	160	303
American Indian or Alaska Native	10	17	27
Asian-Central/South Asian Heritage	2	2	4
Asian-East Asian Heritage	6	4	10
Asian-South East Asian Heritage	1	0	1
Native Hawaiian or Other Pacific Islander	1	0	1
White-Arabic/North African Heritage	3	3	6
White-White/Caucasian/European Heritage	175	172	347
Mixed Race	12	2	14
Unknown	1	1	2

[1]	Baseline Characteristic data are reported for members of the modified Intent-To-Treat Exposed Population, all randomized participants who received at least one dose of IP excluding four participants at one site, which was closed due to Good Clinical Practice (GCP) non-compliance issues in another ViiV sponsored trial.

Outcome Measures

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1. Primary:

Percentage of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) at Week 48 [ Time Frame: Week 48 ]

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Measure Type	Primary
Measure Title	Percentage of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) at Week 48
Measure Description	The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 c/mL at Week 48 was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the randomized phase of the study.
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.
Modified Intent-To-Treat Exposed (mITT-E) Population: all randomized participants who received at least one dose of IP excluding four participants at one site, which was closed due to Good Clinical Practice (GCP) non-compliance issues in another ViiV sponsored trial.

Reporting Groups

Description

DTG 50 mg OD

RAL 400 mg BID

Measured Values

	DTG 50 mg OD	RAL 400 mg BID
Number of Participants Analyzed [units: participants]	354	361
Percentage of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) at Week 48 [units: Percentage of participants]	71	64

Statistical Analysis 1 for Percentage of Participants With HIV-1 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]	0.030
Difference in percentage ^[5]	7.4
95% Confidence Interval	( 0.7 to 14.2 )

[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 of DTG 50 mg and RAL at Week 48 can be concluded if the lower bound of a two-sided 95% confidence interval (CI) for the difference in percentages (DTG - RAL) is greater than -12%. If non-inferiority were established, superiority would be tested at the nominal 5% level based on a pre-specified testing procedure.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	Adjusted difference in proportion which is based on the difference in percentage, adjusted for Baseline (BL) stratification factors.
[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 test of superiority.
[5]	Other relevant estimation information:
	Analysis was adjusted for the BL stratification factors: HIV-1 RNA (<=50000 vs > 50000 c/mL), darunavir-ritonavir use without primary protease inhibitor mutations (yes vs no), and phenotypic susceptibility score (2 vs <2) to background regimen.

2. Secondary:

Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent INI Resistance at Time of Protocol Defined Virology Failure (PDVF) [ Time Frame: Baseline until PDVF up to Week 48 ]

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3. Secondary:

Number of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24 [ Time Frame: Week 24 ]

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4. Secondary:

Number of Participants With Plasma HIV-1 RNA <400 c/mL at Week 24 and Week 48 [ Time Frame: Week 24, Week 48 ]

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5. Secondary:

Absolute Values and Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 16, 24, 32, 40, and 48 ]

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6. Secondary:

Number of Participants With Indicated Post-Baseline HIV-associated Conditions, Excluding Recurrences, and Disease Progressions [ Time Frame: From Baseline (Day 1) until Week 48 ]

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7. Secondary:

Number of Participants With the Indicated Post-Baseline Emergent Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) [ Time Frame: From Baseline until Week 48, including participants with post-treatment events occurring after Week 48 for participants not entering the post-Week 48 Open-Label phase of the study ]

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8. Secondary:

DTG PK Parameters Including Cmax, Cmin, C0, and C0_avg [ Time Frame: Week 4, Week 24, and Week 48 ]

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9. Secondary:

DTG PK Parameters Including AUC(0-tau) [ Time Frame: Week 4, Week 24, and Week 48 ]

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10. Other Pre-specified:

Absolute Values and Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 16, 24, 32, 40, and 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

No publications provided by ViiV Healthcare

Publications automatically indexed to this study:

Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal M, Hagins D, Felizarta F, Madruga J, Reuter T, Newman T, Small CB, Lombaard J, Grinsztejn B, Dorey D, Underwood M, Griffith S, Min S; extended SAILING Study Team. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013 Aug 24;382(9893):700-8. doi: 10.1016/S0140-6736(13)61221-0. Epub 2013 Jul 3. Erratum in: Lancet. 2014 Jan 4;383(9911):30.

Responsible Party:	ViiV Healthcare
ClinicalTrials.gov Identifier:	NCT01231516 History of Changes
Other Study ID Numbers:	111762
Study First Received:	October 21, 2010
Results First Received:	August 15, 2013
Last Updated:	March 20, 2014
Health Authority:	Spain: Agencia Española del Medicamento y Productos Sanitarios Argentina: Ministry of Health - A.N.M.A.T Italy: Comitato Etico Fondazione Centro San Raffaele del Monte Tabor - Via Olgettina, 60 - 20132 Milano Brazil: National Health Surveillance Agency Chile:Ministerio de Salud de Chile 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 Taiwan: Department of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency Hungary: Országos Gyógyszerészeti Intézet South Africa: Medicines Control Council Romania: National Medicines Agency Russia: Roszdrav Nadzor France: Agence Française de Sécurité Sanitaire des Produits de Santé Canada: Health Canada Mexico: COFEPRIS Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Australia: Therapeutic Goods Administration Greece: National Drug Organisation

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