Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
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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 ]
  Show Outcome Measure 1

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 ]
  Show Outcome Measure 2

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 ]
  Show Outcome Measure 7

8.  Secondary:   DTG PK Parameters Including Cmax, Cmin, C0, and C0_avg   [ Time Frame: Week 4, Week 24, and Week 48 ]
  Show Outcome Measure 8

9.  Secondary:   DTG PK Parameters Including AUC(0-tau)   [ Time Frame: Week 4, Week 24, and Week 48 ]
  Hide Outcome Measure 9

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  
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.
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.

Measured Values
    DTG 50 mg OD  
Number of Participants Analyzed  
[units: participants]
 		  340  
DTG PK Parameters Including AUC(0-tau)  
[units: Micrograms*hour per milliliter (µg*hr/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 ]
  Show Outcome Measure 10


  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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