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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.

Verified March 2014 by ViiV Healthcare.
Recruitment status was: Active, not recruiting

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; Intervention Model: Parallel Assignment; Masking: Double Blind (Participant, Care Provider, 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

Overall Participants Analyzed
[Units: Participants]

354

361

715

Age ^[1]
[Units: Years]
Mean (Standard Deviation)

42.6 (10.45)

42.5 (9.81)

42.5 (10.13)

^[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.

Gender ^[1]
[Units: Participants]

Female

107

123

230

Male

247

238

485

^[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.

Race/Ethnicity, Customized ^[1]
[Units: Participants]

African American/African Heritage

143

160

303

American Indian or Alaska Native

Asian-Central/South Asian Heritage

Asian-East Asian Heritage

Asian-South East Asian Heritage

Native Hawaiian or Other Pacific Islander

White-Arabic/North African Heritage

White-White/Caucasian/European Heritage

175

172

347

Mixed Race

Unknown

^[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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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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Measure Type	Secondary
Measure Title	DTG PK Parameters Including AUC(0-tau)
Measure Description	AUC is defined as the area under the DTG concentration-time curve as a measure of drug exposure over time. AUC(0-tau) is defined as the area under the plasma concentration-time curve from time zero to time tau over a dosing interval at steady state, where tau is the length of the dosing interval of DTG. AUC was assessed by population pharmacokinetic (PK) modeling using sparse PK samples which were collected as follows: one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 4, one pre-dose sample at Week 24, and one pre-dose sample and one post-dose sample at 1 to 3 hours/4 to 12 hours at Week 48.
Time Frame	Week 4, Week 24, and Week 48

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.
PK Concentration Population: all participants who received DTG, underwent sparse PK sampling during the study, and provided evaluable DTG plasma concentration data. Only those participants available at the indicated time points were assessed.

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 continued to have access to DTG in the Open-Label phase of the study.

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 continued to have access to DTG in the Open-Label phase of the study.

Measured Values

	DTG 50 mg OD
Participants Analyzed [Units: Participants]	340
DTG PK Parameters Including AUC(0-tau) [Units: Microgramshour per milliliter (µghr/mL] Geometric Mean (Geometric Coefficient of Variation)	44.7 (40.5%)

No statistical analysis provided for DTG PK Parameters Including AUC(0-tau)

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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