ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01231516
Recruitment Status : Active, not recruiting
First Posted : November 1, 2010
Results First Posted : January 31, 2014
Last Update Posted : September 3, 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
Enrollment 724

Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description 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. 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.
Period Title: 48 Week Double-blind Phase
Started 357 362
Completed 299 283
Not Completed 58 79
Reason Not Completed
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 Title: Open-label Phase
Started 295 [1] 27 [2]
Ongoing at the Time of Analysis 282 23
Completed 0 1
Not Completed 295 26
Reason Not Completed
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.
Arm/Group Title DTG 50 mg OD RAL 400 mg BID Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 354 361 715
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 354 participants 361 participants 715 participants
42.6  (10.45) 42.5  (9.81) 42.5  (10.13)
[1]
Measure Description: 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] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 354 participants 361 participants 715 participants
Female
107
  30.2%
123
  34.1%
230
  32.2%
Male
247
  69.8%
238
  65.9%
485
  67.8%
[1]
Measure Description: 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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 354 participants 361 participants 715 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]
Measure Description: 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.
1.Primary Outcome
Title Percentage of Participants With HIV-1 RNA <50 Copies/Milliliter (c/mL) at Week 48
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 354 361
Measure Type: Number
Unit of Measure: Percentage of participants
71 64
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DTG 50 mg OD, RAL 400 mg BID
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value 0.030
Comments P-value is for test of superiority.
Method Cochran-Mantel-Haenszel
Comments Adjusted difference in proportion which is based on the difference in percentage, adjusted for Baseline (BL) stratification factors.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 7.4
Confidence Interval (2-Sided) 95%
0.7 to 14.2
Estimation Comments 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 Outcome
Title 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)
Hide Description For par. meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure and Baseline were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) virologic non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 16, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 or (B) virologic rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >1 log10 copies/mL above the nadir value, where nadir is >=400 copies/mL.Treatment-emergent IN mutations are those detected at the time of PDVF but not at Baseline.
Time Frame Baseline until PDVF up to Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT-E Population
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 354 361
Measure Type: Number
Unit of Measure: Participants
4 17
3.Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24
Hide Description The number of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 c/mL at Week 24 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 24 as nonresponders, as well as participants who switched their concomitant ART prior to Week 24 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 measurement through Week 24 (within window) while the participant was on-treatment. The result below corresponds to the Week 24 interim analysis.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT-E Population
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 354 361
Measure Type: Number
Unit of Measure: Participants
281 252
4.Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA <400 c/mL at Week 24 and Week 48
Hide Description The number of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <400 c/mL at the visit of interest 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 the visit of interest as nonresponders, as well as participants who switched their concomitant ART prior to the visit of interest 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 measurment (within window) for the timepoint of interest while the participant was on-treatment.
Time Frame Week 24, Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT-E Population
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 354 361
Measure Type: Number
Unit of Measure: Participants
Week 24 307 287
Week 48 278 257
5.Secondary Outcome
Title 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
Hide Description The absolute value for CD4+ cell count (cells per millimeters cubed [mm^3]) was assessed at Baseline (BL), Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40 and Week 48. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline; Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT-E Population. Only those participants available at the indicated time points were assessed. The number of participants assessed at each visit is indicated by "n=X, X".
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 354 361
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^3
Absolute value, BL, n=354, 361
204.5
(88 to 368)
193.0
(96 to 365)
Absolute value, Week 4, n=341, 351
266.0
(164 to 416)
253.0
(153 to 425)
Absolute value, Week 8, n=338, 346
280.0
(179 to 423)
268.0
(163 to 445)
Absolute value, Week 12, n=335, 345
296.0
(188 to 451)
289.0
(174 to 443)
Absolute value, Week 16, n=327, 338
299.0
(179 to 462)
293.0
(186 to 460)
Absolute value, Week 24, n=326, 326
334.5
(201 to 488)
326.5
(198 to 473)
Absolute value, Week 32, n=309, 309
332.0
(229 to 482)
338.0
(215 to 484)
Absolute value, Week 40, n=299, 292
376.0
(239 to 523)
349.0
(227 to 500)
Absolute value, Week 48, n=294, 283
385.0
(244 to 565)
379.0
(250 to 521)
Change from BL, Week 4, n=341, 351
53.0
(0 to 109)
45.0
(5 to 99)
Change from BL, Week 8, n=338, 346
60.5
(15 to 117)
59.0
(12 to 124)
Change from BL, Week 12, n=335, 345
74.0
(25 to 135)
75.0
(22 to 141)
Change from BL, Week 16, n=327, 338
76.0
(20 to 156)
79.5
(28 to 158)
Change from BL, Week 24, n=326, 326
99.0
(34 to 184)
93.0
(46 to 166)
Change from BL, Week 32, n=309, 309
107.0
(49 to 188)
116.0
(52 to 173)
Change from BL, Week 40, n=299, 292
125.0
(57 to 212)
117.5
(52 to 192)
Change from BL, Week 48, n=294, 283
144.0
(73 to 242)
137.0
(67 to 224)
6.Secondary Outcome
Title Number of Participants With Indicated Post-Baseline HIV-associated Conditions, Excluding Recurrences, and Disease Progressions
Hide Description Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline (BS) to a CDC CAT C event (EV); CDC CAT B at BS to a CDC CAT C EV; CDC CAT C at BS to a new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.
Time Frame From Baseline (Day 1) until Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT-E Population
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 354 361
Measure Type: Number
Unit of Measure: Participants
Any CAT 20 19
CAT B 11 11
CAT C 10 6
Death 0 3
Progression from CAT A to CAT C 2 1
Progression from CAT B to CAT C 0 1
Progression from CAT C to New CAT C 8 3
Progression from CAT A, B, or C to Death 0 3
7.Secondary Outcome
Title Number of Participants With the Indicated Post-Baseline Emergent Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs)
Hide 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, 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 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 DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of IP (i.e., DTG or RAL)
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 357 362
Measure Type: Number
Unit of Measure: Participants
ALT 47 46
Albumin 4 3
ALP 27 42
AST 49 52
CO2 content/bicarbonate 97 109
Cholesterol 99 103
CK 28 29
Creatinine 18 13
Hyperglycaemia 71 80
Hyperkalemia 7 6
Hypernatremia 5 7
Hypoglycaemia 21 14
Hypokalemia 37 41
Hyponatremia 76 79
LDL cholesterol calculation 68 82
Lipase 63 68
Total bilirubin 56 53
Triglycerides 14 24
Hemoglobin 19 27
Platelet count 36 32
Total neutrophils 49 49
White Blood Cell count 19 29
8.Secondary Outcome
Title DTG PK Parameters Including Cmax, Cmin, C0, and C0_avg
Hide Description The maximal concentration (Cmax), and the minimal concentration (Cmin) were 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. DTG predose concentration (C0) at Week 4, Week 24, and Week 48 as well as the average C0 (C0_avg) , Cmax and Cmin were estimated and reported here.
Time Frame Week 4, Week 24, and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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. The number of participants assessed at each time point is indicated by "n=X".
Arm/Group Title DTG 50 mg OD
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 342
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram/milliliter (µg/mL)
C0, Week 4, Pre-dose, n=329
0.786
(143%)
C0, Week 24, Pre-dose, n=298
0.940
(132%)
C0, Week 48, Pre-dose, n=276
0.932
(152%)
C0_avg, n=342
0.926
(131%)
Cmax, n=340
3.21
(26.7%)
Cmin, n=340
0.849
(76.5%)
9.Secondary Outcome
Title DTG PK Parameters Including AUC(0-tau)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title DTG 50 mg OD
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 340
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Micrograms*hour per milliliter (µg*hr/mL
44.7
(40.5%)
10.Other Pre-specified Outcome
Title 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
Hide Description The absolute value data for CD8+ cell count (cells per millimeters cubed [mm^3]) were only reported on a per-participant basis and were not summarized.
Time Frame Baseline; Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT-E Population
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the randomized treatment period (up to Week 48).
Adverse Event Reporting Description SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product. Also included are post-treatment events occurring after Week 48 for participants not entering the post-Week 48 Open-Label phase of the study.
 
Arm/Group Title DTG 50 mg OD RAL 400 mg BID
Hide Arm/Group Description 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. 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 continued to supply RAL in the Open-Label Phase until it was commercially available.
All-Cause Mortality
DTG 50 mg OD RAL 400 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
DTG 50 mg OD RAL 400 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   33/357 (9.24%)   42/362 (11.60%) 
Blood and lymphatic system disorders     
Anaemia  1  0/357 (0.00%)  2/362 (0.55%) 
Coagulation factor deficiency  1  0/357 (0.00%)  1/362 (0.28%) 
Disseminated intravascular coagulation  1  1/357 (0.28%)  0/362 (0.00%) 
Methaemoglobinaemia  1  1/357 (0.28%)  0/362 (0.00%) 
Cardiac disorders     
Angina pectoris  1  1/357 (0.28%)  0/362 (0.00%) 
Cardiomyopathy  1  0/357 (0.00%)  1/362 (0.28%) 
Coronary artery disease  1  0/357 (0.00%)  1/362 (0.28%) 
Eye disorders     
Iridocyclitis  1  0/357 (0.00%)  1/362 (0.28%) 
Gastrointestinal disorders     
Pancreatitis  1  2/357 (0.56%)  1/362 (0.28%) 
Abdominal pain  1  1/357 (0.28%)  0/362 (0.00%) 
Anal ulcer  1  0/357 (0.00%)  1/362 (0.28%) 
Intestinal obstruction  1  0/357 (0.00%)  1/362 (0.28%) 
Oral mucosal blistering  1  0/357 (0.00%)  1/362 (0.28%) 
Pancreatitis acute  1  0/357 (0.00%)  1/362 (0.28%) 
Pancreatitis relapsing  1  1/357 (0.28%)  0/362 (0.00%) 
Rectal haemorrhage  1  1/357 (0.28%)  0/362 (0.00%) 
Small intestine obstruction  1  0/357 (0.00%)  1/362 (0.28%) 
General disorders     
Non-cardiac chest pain  1  0/357 (0.00%)  1/362 (0.28%) 
Pyrexia  1  1/357 (0.28%)  0/362 (0.00%) 
Hepatobiliary disorders     
Hepatitis  1  2/357 (0.56%)  1/362 (0.28%) 
Hepatotoxicity  1  1/357 (0.28%)  1/362 (0.28%) 
Acute hepatic failure  1  0/357 (0.00%)  1/362 (0.28%) 
Liver disorder  1  1/357 (0.28%)  0/362 (0.00%) 
Immune system disorders     
Immune reconstitution inflammatory syndrome  1  1/357 (0.28%)  0/362 (0.00%) 
Sarcoidosis  1  0/357 (0.00%)  1/362 (0.28%) 
Infections and infestations     
Pneumonia  1  2/357 (0.56%)  4/362 (1.10%) 
Gastroenteritis  1  1/357 (0.28%)  1/362 (0.28%) 
Postoperative wound infection  1  0/357 (0.00%)  2/362 (0.55%) 
Anal abscess  1  0/357 (0.00%)  1/362 (0.28%) 
Bronchitis  1  1/357 (0.28%)  0/362 (0.00%) 
Bronchopneumonia  1  0/357 (0.00%)  1/362 (0.28%) 
Cellulitis  1  0/357 (0.00%)  1/362 (0.28%) 
Cytomegalovirus oesophagitis  1  0/357 (0.00%)  1/362 (0.28%) 
Disseminated tuberculosis  1  0/357 (0.00%)  1/362 (0.28%) 
Extrapulmonary tuberculosis  1  0/357 (0.00%)  1/362 (0.28%) 
Gangrene  1  0/357 (0.00%)  1/362 (0.28%) 
Gas gangrene  1  0/357 (0.00%)  1/362 (0.28%) 
Gastroenteritis viral  1  1/357 (0.28%)  0/362 (0.00%) 
Genital herpes  1  0/357 (0.00%)  1/362 (0.28%) 
Histoplasmosis disseminated  1  1/357 (0.28%)  0/362 (0.00%) 
Infection  1  0/357 (0.00%)  1/362 (0.28%) 
Infective myositis  1  0/357 (0.00%)  1/362 (0.28%) 
Intervertebral discitis  1  0/357 (0.00%)  1/362 (0.28%) 
Joint abscess  1  1/357 (0.28%)  0/362 (0.00%) 
Legionella infection  1  1/357 (0.28%)  0/362 (0.00%) 
Lower respiratory tract infection  1  1/357 (0.28%)  0/362 (0.00%) 
Orchitis  1  0/357 (0.00%)  1/362 (0.28%) 
Parvovirus infection  1  1/357 (0.28%)  0/362 (0.00%) 
Pneumonia staphylococcal  1  0/357 (0.00%)  1/362 (0.28%) 
Pneumonia viral  1  1/357 (0.28%)  0/362 (0.00%) 
Progressive multifocal leukoencephalopathy  1  0/357 (0.00%)  1/362 (0.28%) 
Subcutaneous abscess  1  0/357 (0.00%)  1/362 (0.28%) 
Toxoplasmosis  1  1/357 (0.28%)  0/362 (0.00%) 
Tuberculosis liver  1  1/357 (0.28%)  0/362 (0.00%) 
Wound infection  1  0/357 (0.00%)  1/362 (0.28%) 
Wound infection staphylococcal  1  0/357 (0.00%)  1/362 (0.28%) 
Injury, poisoning and procedural complications     
Alcohol poisoning  1  1/357 (0.28%)  0/362 (0.00%) 
Fibula fracture  1  1/357 (0.28%)  0/362 (0.00%) 
Overdose  1  1/357 (0.28%)  0/362 (0.00%) 
Upper limb fracture  1  1/357 (0.28%)  0/362 (0.00%) 
Investigations     
Blood alkaline phosphatase increased  1  0/357 (0.00%)  1/362 (0.28%) 
Metabolism and nutrition disorders     
Dehydration  1  0/357 (0.00%)  2/362 (0.55%) 
Hyperglycaemia  1  0/357 (0.00%)  1/362 (0.28%) 
Hyperkalaemia  1  1/357 (0.28%)  0/362 (0.00%) 
Lactic acidosis  1  0/357 (0.00%)  1/362 (0.28%) 
Musculoskeletal and connective tissue disorders     
Rhabdomyolysis  1  2/357 (0.56%)  0/362 (0.00%) 
Arthritis  1  0/357 (0.00%)  1/362 (0.28%) 
Back pain  1  1/357 (0.28%)  0/362 (0.00%) 
Intervertebral disc protrusion  1  0/357 (0.00%)  1/362 (0.28%) 
Myositis  1  1/357 (0.28%)  0/362 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma  1  0/357 (0.00%)  1/362 (0.28%) 
Cervix carcinoma  1  0/357 (0.00%)  1/362 (0.28%) 
Immunoblastic lymphoma  1  0/357 (0.00%)  1/362 (0.28%) 
Metastatic neoplasm  1  1/357 (0.28%)  0/362 (0.00%) 
Vulval neoplasm  1  0/357 (0.00%)  1/362 (0.28%) 
Nervous system disorders     
Cerebrovascular accident  1  0/357 (0.00%)  2/362 (0.55%) 
Cerebrovascular disorder  1  1/357 (0.28%)  0/362 (0.00%) 
Headache  1  0/357 (0.00%)  1/362 (0.28%) 
Psychiatric disorders     
Suicidal ideation  1  4/357 (1.12%)  1/362 (0.28%) 
Alcohol withdrawal syndrome  1  2/357 (0.56%)  0/362 (0.00%) 
Depression  1  2/357 (0.56%)  0/362 (0.00%) 
Mental status changes  1  1/357 (0.28%)  1/362 (0.28%) 
Suicide attempt  1  2/357 (0.56%)  0/362 (0.00%) 
Alcohol abuse  1  1/357 (0.28%)  0/362 (0.00%) 
Anxiety  1  0/357 (0.00%)  1/362 (0.28%) 
Depression suicidal  1  0/357 (0.00%)  1/362 (0.28%) 
Substance abuse  1  0/357 (0.00%)  1/362 (0.28%) 
Renal and urinary disorders     
Renal failure acute  1  2/357 (0.56%)  1/362 (0.28%) 
Nephrolithiasis  1  1/357 (0.28%)  0/362 (0.00%) 
Reproductive system and breast disorders     
Cervical dysplasia  1  0/357 (0.00%)  1/362 (0.28%) 
Uterine haemorrhage  1  0/357 (0.00%)  1/362 (0.28%) 
Respiratory, thoracic and mediastinal disorders     
Alveolar proteinosis  1  0/357 (0.00%)  1/362 (0.28%) 
Dyspnoea  1  0/357 (0.00%)  1/362 (0.28%) 
Epistaxis  1  0/357 (0.00%)  1/362 (0.28%) 
Respiratory distress  1  1/357 (0.28%)  0/362 (0.00%) 
Sinus disorder  1  0/357 (0.00%)  1/362 (0.28%) 
Skin and subcutaneous tissue disorders     
Rash pruritic  1  0/357 (0.00%)  1/362 (0.28%) 
Vascular disorders     
Aortic arteriosclerosis  1  0/357 (0.00%)  1/362 (0.28%) 
Arteriosclerosis  1  0/357 (0.00%)  1/362 (0.28%) 
Hypertension  1  0/357 (0.00%)  1/362 (0.28%) 
Malignant hypertension  1  0/357 (0.00%)  1/362 (0.28%) 
Peripheral arterial  1  0/357 (0.00%)  1/362 (0.28%) 
Occlusive disease  1  0/357 (0.00%)  1/362 (0.28%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DTG 50 mg OD RAL 400 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   178/357 (49.86%)   173/362 (47.79%) 
Gastrointestinal disorders     
Diarrhoea  1  71/357 (19.89%)  64/362 (17.68%) 
Nausea  1  29/357 (8.12%)  29/362 (8.01%) 
Vomiting  1  20/357 (5.60%)  20/362 (5.52%) 
General disorders     
Fatigue  1  15/357 (4.20%)  24/362 (6.63%) 
Infections and infestations     
Upper respiratory tract infection  1  38/357 (10.64%)  29/362 (8.01%) 
Influenza  1  24/357 (6.72%)  25/362 (6.91%) 
Nasopharyngitis  1  23/357 (6.44%)  22/362 (6.08%) 
Urinary tract infection  1  26/357 (7.28%)  18/362 (4.97%) 
Nervous system disorders     
Headache  1  33/357 (9.24%)  30/362 (8.29%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  33/357 (9.24%)  24/362 (6.63%) 
Skin and subcutaneous tissue disorders     
Rash  1  19/357 (5.32%)  18/362 (4.97%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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.
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
Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01231516     History of Changes
Other Study ID Numbers: 111762
First Submitted: October 21, 2010
First Posted: November 1, 2010
Results First Submitted: August 15, 2013
Results First Posted: January 31, 2014
Last Update Posted: September 3, 2018