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

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ClinicalTrials.gov Identifier: NCT01231516
Recruitment Status : Active, not recruiting
First Posted : November 1, 2010
Results First Posted : January 31, 2014
Last Update Posted : May 16, 2018
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

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
Interventions: Drug: GSK1349572
Drug: Raltegravir
Drug: GSK1349572 Placebo
Drug: Raltegravir Placebo

  Participant Flow

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
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

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 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.
Sex: Female, Male [1] 
[Units: Participants]
Count of Participants 		     
Female      107  30.2%      123  34.1%      230  32.2% 
Male      247  69.8%      238  65.9%      485  67.8% 
[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   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

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 ]
  Show Outcome Measure 3

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 ]
  Show Outcome Measure 4

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 ]
  Show Outcome Measure 5

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 ]
  Show Outcome Measure 6

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  

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 
Participants Analyzed   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


  Other Adverse Events


  Limitations and Caveats

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
No text entered.


  More Information