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A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen. (VIKING-3)

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ClinicalTrials.gov Identifier: NCT01328041
Recruitment Status : Completed
First Posted : April 4, 2011
Results First Posted : July 21, 2014
Last Update Posted : January 7, 2016
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Infection, Human Immunodeficiency Virus
Intervention Drug: dolutegravir
Enrollment 183
Recruitment Details Participants (par.) having documented Human immunodeficiency virus type 1 (HIV-1) infection with a plasma HIV-1 Ribonucleic acid(RNA) >=500 copies per milliliter (c/mL) at Screening, Antiretroviral therapy (ART)-experienced and on stable ART for at least one month prior to Screening were enrolled
Pre-assignment Details A total of 139 par. were screen failures and 183 par. entered the single arm, open-label study.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description Participants received dolutegravir (DTG) 50 milligrams (mg) twice a day (BID).
Period Title: Overall Study
Started 183
Completed 126
Not Completed 57
Reason Not Completed
Adverse Event             7
Lack of Efficacy             27
Protocol Violation             7
Lost to Follow-up             7
Physician Decision             2
Withdrawal by Subject             7
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description Participants received DTG 50 mg BID.
Overall Number of Baseline Participants 183
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 183 participants
48
(19 to 67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 183 participants
Female
42
  23.0%
Male
141
  77.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 183 participants
African American/African Heritage 49
American Indian or Alaska Native and White 1
Asian-Central/South Asian Heritage 1
White 130
White and African American/African Heritage 2
1.Primary Outcome
Title Mean Change From Baseline in Plasma HIV-1 RNA at Day 8
Hide Description Mean change from Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 8 was calculated as the Day 8 value minus the Baseline value. The last observation was carried forward if a participant had missed the Day 8 visit. The Baseline observation was carried forward if a participant had discontinued the treatment before Day 8. Blood samples for assessment of HIV-1 RNA levels were collected at Baseline and Day 8.
Time Frame Baseline and Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat-Exposed (ITT-E) Population: all participants who received at least one dose of study drug. Only participants who had Day 8 observations were considered for analysis.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 182
Mean (Standard Deviation)
Unit of Measure: log10 copies/milliliter (mL)
-1.432  (0.6070)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dolutegravir 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The P value was derived by the null hypothesis testing of no change from Baseline in HIV-1 RNA at Day 8 at the two-sided 5% significance level using a single sample t-test.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter T distribution
Estimated Value -1.432
Confidence Interval (2-Sided) 95%
-1.520 to -1.343
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 24
Hide Description The number of participants who had viral load <50 copies/mL at Week 24 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI [due to missing data/discontinuation of investigational product prior to the visit window]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Measure Type: Number
Unit of Measure: participants
126
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dolutegravir 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 69
Confidence Interval (2-Sided) 95%
62 to 76
Estimation Comments The estimated value represents the percentage of participants with HIV-1 RNA less than 50 copies/mL at Week 24.
3.Primary Outcome
Title Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48
Hide Description The number of participants who had viral load <50 copies/mL at Week 48 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI [due to missing data/discontinuation of investigational product prior to the visit window]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Measure Type: Number
Unit of Measure: participants
116
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dolutegravir 50 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 63
Confidence Interval (2-Sided) 95%
56 to 70
Estimation Comments The estimated value represents the percentage of participants with HIV-1 RNA less than 50 copies/mL at Week 48.
4.Primary Outcome
Title Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
Hide Description An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.
Time Frame From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of study drug
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Measure Type: Number
Unit of Measure: participants
Any AE 169
Any SAE 46
5.Primary Outcome
Title Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale
Hide Description An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. AE/SAE severity was graded according to the DAIDS grading scale. The DAIDS displays events as Grades 1-4 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, potentially life threatening.
Time Frame From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Measure Type: Number
Unit of Measure: participants
Grade 1 45
Grade 2 64
Grade 3 44
Grade 4 16
6.Primary Outcome
Title Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade
Hide Description The severity of clinical chemistry toxicities was graded according to the DAIDS toxicity scale. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.
Time Frame From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Measure Type: Number
Unit of Measure: participants
Grade 1 49
Grade 2 67
Grade 3 43
Grade 4 16
7.Primary Outcome
Title Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade
Hide Description The severity of hematology toxicities was graded according to the DAIDS. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.
Time Frame From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Measure Type: Number
Unit of Measure: Participants
Grade 1 31
Grade 2 15
Grade 3 4
Grade 4 2
8.Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Hide Description The number of participants with plasma HIV-1 RNA less than 400 and 50 copies (c)/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40 and 48 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI [due to missing data/discontinuation of investigational product prior to the visit window]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the par. was on treatment within the VOI analysis window
Time Frame Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Measure Type: Number
Unit of Measure: participants
HIV-1 RNA <50 c/mL, Baseline 1
HIV-1 RNA <50 c/mL, Day 8 28
HIV-1 RNA <50 c/mL, Week 4 98
HIV-1 RNA <50 c/mL, Week 8 112
HIV-1 RNA <50 c/mL, Week 12 116
HIV-1 RNA <50 c/mL, Week 16 116
HIV-1 RNA <50 c/mL, Week 24 126
HIV-1 RNA <50 c/mL, Week 32 117
HIV-1 RNA <50 c/mL, Week 40 108
HIV-1 RNA <50 c/mL, Week 48 116
HIV-1 RNA <400 c/mL, Baseline 8
HIV-1 RNA <400 c/mL, Day 8 82
HIV-1 RNA <400 c/mL, Week 4 145
HIV-1 RNA <400 c/mL, Week 8 146
HIV-1 RNA <400 c/mL, Week 12 142
HIV-1 RNA <400 c/mL, Week 16 139
HIV-1 RNA <400 c/mL, Week 24 135
HIV-1 RNA <400 c/mL, Week 32 127
HIV-1 RNA <400 c/mL, Week 40 119
HIV-1 RNA <400 c/mL, Week 48 125
9.Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion
Hide Description The number of participants with plasma HIV-1 RNA less than 400 and 50 copies (c)/mL was assessed at Weeks 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 using data of observed cases. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame From Week 48 every 12 weeks up to study completion.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Measure Type: Number
Unit of Measure: Participants
HIV-1 RNA <50 c/mL, Week 48, n =146 121
HIV-1 RNA <50 c/mL, Week 60, n=142 110
HIV-1 RNA <50 c/mL, Week 72, n=138 116
HIV-1 RNA <50 c/mL, Week 84, n=138 108
HIV-1 RNA <50 c/mL, Week 96, n=120 101
HIV-1 RNA <50 c/mL, Week 108, n=98 81
HIV-1 RNA <50 c/mL, Week 120, n=82 72
HIV-1 RNA <50 c/mL, Week 132, n=61 49
HIV-1 RNA <50 c/mL, Week 144, n=45 37
HIV-1 RNA <50 c/mL, Week 156, n=32 28
HIV-1 RNA <50 c/mL, Week 168, n=24 20
HIV-1 RNA <50 c/mL, Week 180, n=6 4
HIV-1 RNA <400 c/mL, Week 48, n=146 134
HIV-1 RNA <400 c/mL, Week 60, n=142 131
HIV-1 RNA <400 c/mL, Week 72, n=138 130
HIV-1 RNA <400 c/mL, Week 84, n=138 127
HIV-1 RNA <400 c/mL, Week 96, n=120 111
HIV-1 RNA <400 c/mL, Week 108, n=98 92
HIV-1 RNA <400 c/mL, Week 120, n=82 80
HIV-1 RNA <400 c/mL, Week 132, n=61 59
HIV-1 RNA <400 c/mL, Week 144, n=45 44
HIV-1 RNA <400 c/mL, Week 156, n=32 31
HIV-1 RNA <400 c/mL, Week 168, n=24 23
HIV-1 RNA <400 c/mL, Week 180, n=6 5
10.Secondary Outcome
Title Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion
Hide Description Mean change from Baseline in plasma HIV-1 RNA was assesseed at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, 48 , 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 using data of the observed cases. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study completion (Up to Week 180)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants with data available at the indicated time points were considered for analysis (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Mean (Standard Deviation)
Unit of Measure: Log10 copies/mL
Day 8, n=182 -1.432  (0.607)
Week 4, n=180 -2.088  (0.885)
Week 8, n=179 -2.101  (0.987)
Week 12, n=174 -2.113  (1.069)
Week 16, n=165 -2.216  (1.005)
Week 24, n=164 -2.211  (1.023)
Week 32, n=146 -2.373  (0.926)
Week 40, n=144 -2.301  (0.955)
Week 48, n=146 -2.321  (0.981)
Week 60, n=142 -2.356  (0.928)
Week 72, n=138 -2.390  (0.941)
Week 84, n=138 -2.311  (0.996)
Week 96, n=120 -2.346  (1.008)
Week 108, n=98 -2.394  (0.966)
Week 120, n=82 -2.515  (0.904)
Week 132, n=61 -2.456  (0.988)
Week 144, n=45 -2.585  (0.983)
Week 156, n=32 -2.595  (1.009)
Week 168, n=24 -2.719  (0.898)
Week 180, n=6 -2.425  (1.557)
11.Secondary Outcome
Title Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48
Hide Description Absolute values for CD4+ cell counts were assessed at Baseline, Day 8 and Weeks 4, 8, 12, 16, and 24, and absolute values for CD8+ cell counts were assessed at Baseline and Weeks 4, 12, 24, and 48.
Time Frame Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants with data available at the indicated time points were considered for analysis (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Median (Inter-Quartile Range)
Unit of Measure: Cells per millimeters cubed (cells/mm^3)
CD4+, Baseline, n=183
140.0
(40.0 to 330.0)
CD4+, Day 8, n=181
170.0
(60.0 to 350.0)
CD4+, Week 4, n=178
185.0
(80.0 to 350.0)
CD4+, Week 8, n=178
210.0
(100.0 to 350.0)
CD4+, Week 12, n=171
210.0
(110.0 to 360.0)
CD4+, Week 16, n=165
210.0
(130.0 to 400.0)
CD4+, Week 24, n=163
250.0
(130.0 to 420.0)
CD4+, Week 32, n=147
270.0
(170.0 to 440.0)
CD4+, Week 40, n=143
290.0
(200.0 to 440.0)
CD4+, Week 48, n=145
310.0
(200.0 to 450.0)
CD8+, Week 4, n=181
860.0
(540.0 to 1220.0)
CD8+, Week 4, n=176
970.0
(655.0 to 1405.0)
CD8+, Week 12, n=170
1015.0
(730.0 to 1460.0)
CD8+, Week 24, n=154
1020.0
(690.0 to 1460.0)
CD8+, Week 48, n=140
1000.0
(720.0 to 1380.0)
12.Secondary Outcome
Title Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion
Hide Description Median change from Baseline in CD4+ cell counts was assessed at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180. v
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants with data available at the indicated time points were considered for analysis (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Median (Inter-Quartile Range)
Unit of Measure: Cells per millimeters cubed (cells/mm^3)
CD4+, Day 8, n=181
20.0
(0.0 to 60.0)
CD4+, Week 4, n=178
30.0
(0.0 to 71.0)
CD4+, Week 8, n=178
40.0
(0.0 to 81.0)
CD4+, Week 12, n=171
50.0
(0.0 to 100.0)
CD4+, Week 16, n=165
60.0
(20.0 to 130.0)
CD4+, Week 24, n=163
61.0
(20.0 to 130.0)
CD4+, Week 32, n=147
100.0
(20.0 to 160.0)
CD4+, Week 40, n=143
90.0
(30.0 to 180.0)
CD4+, Week 48, n=145
110.0
(40.0 to 190.0)
CD4+, Week 60, n=142
120.0
(50.0 to 210.0)
CD4+, Week 72, n=138
140.0
(60.0 to 231.0)
CD4+, Week 84, n=137
150.0
(80.0 to 240.0)
CD4+, Week 96, n=117
160.0
(80.0 to 270.0)
CD4+, Week 108, n=98
180.5
(80.0 to 280.0)
CD4+, Week 120, n=82
180.0
(100.0 to 280.0)
CD4+, Week 132, n=61
221.0
(100.0 to 320.0)
CD4+, Week 144, n=46
205.0
(130.0 to 350.0)
CD4+, Week 156, n=32
225.0
(155. to 345.0)
CD4+, Week168, n=24
265.0
(155.0 to 380.0)
CD4+, Week180, n=6
170.5
(140.0 to 230.0)
13.Secondary Outcome
Title Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48
Hide Description The ratio of CD4+/CD8+ cell count (measured in cells/mm^3) was assessed at Baseline and at Weeks 4, 12, 24, and 48. The ratio was calculated as the CD4+ cell count divided by CD8+ cell count.
Time Frame Baseline; Weeks 4, 12, 24, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants with data available at the indicated time points were considered for analysis (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Median (Inter-Quartile Range)
Unit of Measure: ratio
Baseline, n=180
0.15
(0.05 to 0.34)
Week 4, n=176
0.19
(0.09 to 0.37)
Week 12, n=170
0.21
(0.10 to 0.46)
Week 24, n=154
0.26
(0.14 to 0.46)
Week 48, n=140
0.32
(0.19 to 0.52)
14.Secondary Outcome
Title Number of Participants With HIV-1 Disease Progression (Acquired Immune Deficiency Syndrome [AIDS] or Death)
Hide Description The number of participants with HIV-1 disease progression (AIDS or death) was assessed per the Centers for Disease Control and Prevention (CDC) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. The CDC classifies HIV infection as Category A (participants with asymptomatic HIV infection, acute HIV infection with accompanying illness, or persistent generalized lymphadenopathy), Category B (participants with symptomatic non-AIDS condition, i.e., conditions that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection), and Category C (includes AIDS indicator conditions as defined by diagnostic or presumptive measures).
Time Frame From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Measure Type: Number
Unit of Measure: Participants
Progression from CDC Class A to Class C Event 1
Progression from CDC Class B to Class C Event 2
Progression from CDC Class C to New Class C Event 6
Progression from Classes A, B, or C to Death 2
15.Secondary Outcome
Title Cmax and Ctau of DTG
Hide Description The maximum plasma concentration (Cmax) and the concentration at the end of a dosing interval (Ctau) of DTG were assessed by a population pharmacokinetic (PK) modeling approach using pooled DTG PK data from multiple studies. For this study, blood samples for pharmacokinetic assessments were collected pre-dose on Day 8 and at Weeks 4 and 24, at 1-3 hours post-dose on Day 8, and at 1-3 hours or 4-12 hours post-dose at Weeks 4 and 24.
Time Frame Day 8, Week 4, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) Concentration Population: all subjects who received DTG, had undergone PK sampling during the study, and provided evaluable DTG plasma concentration data.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Geometric Mean (95% Confidence Interval)
Unit of Measure: Micrograms per milliliter (µg/mL)
Cmax
4.74
(4.18 to 5.36)
Ctau
2.60
(2.15 to 3.15)
16.Secondary Outcome
Title AUC(0-tau) and AUC(0-24) of DTG
Hide Description The area under the time concentration curve over the dosing interval (AUC[0-tau]) and from 0 to 24 hours (AUC[0-24]) of DTG was assessed by a population PK modeling approach using pooled DTG PK data from multiple studies. For this study, blood samples for pharmacokinetic assessments were collected pre-dose on Day 8 and at Weeks 4 and 24, at 1-3 hours post-dose on Day 8, and at 1-3 hours or 4-12 hours post-dose at Weeks 4 and 24.
Time Frame Day 8, Week 4, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) Concentration Population: all subjects who received DTG, had undergone PK sampling during the study, and provided evaluable DTG plasma concentration data.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 183
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg*hour/mL
AUC(0-tau)
36.7
(35.0 to 38.6)
AUC(0-24)
73.5
(70.0 to 77.1)
17.Secondary Outcome
Title C0 Assessment of DTG
Hide Description The plasma DTG concentration immediately prior to dosing at steady state (C0) was assessed at Day 8, Week 4, and Week 24. Blood samples for pharmacokinetic assessments were collected pre-dose and 1-3 hours post-dose on Day 8 and at Week 4 and 4-12 hours post-dose at Week 24. Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Pharmacokinetic Parameter Population.
Time Frame Day 8, Week 4, and Week 24
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Hide Analysis Population Description
Pharmacokinetic (PK) Parameter Population: all participants who received DTG, underwent PK sampling during the study, and provided an evaluable estimate of C0. Only participants with data available at the indicated time points were considered for analysis.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 161
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg/mL
Day 8, n=148
2.36
(91%)
Week 4, n=161
1.90
(113%)
Week 24, n=135
2.14
(93%)
18.Secondary Outcome
Title Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF) as a Measure of Genotypic Resistance
Hide Description An analysis of changes at specific amino acids in the IN coding region associated with resistance to raltegravir, elvitegravir, or DTG was performed at Day 1 and at the time of PDVF. PDVF is a <0.5 log10 copies(c)/mL decrease in plasma HIV-1 RNA at Day 8 unless the absolute value is <400 c/mL. PDVF after Day 8 is defined as virological non-respones (decrease in plasma HIV-1 RNA of <1 log10 c/mL by Week 16, with subsequent confirmation, unless plasma HIV-1 RNA <400 c/mL and confirmed plasma HIV-1 RNA levels >=400 c/mL on or after Week 24) and virological rebound (confirmed rebound in plasma HIV-1 RNA levels to >=400 c/mL after prior confirmed suppression to <400 c/mL and confirmed plasma HIV-1 RNA levels >1 log10 c/mL above the nadir value [nadir: >=400 c/mL]).
Time Frame From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
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Hide Analysis Population Description
PDVF Genotypic Resistance Populations: all participants in the ITT-E Population with available on-treatment genotypic resistance data at the time of PDVF. Only participants with Baseline IN mutations with PDVF who had paired Baseline and time of PDVF samples were considered for analysis.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 42
Measure Type: Number
Unit of Measure: participants
Any IN mutation 25
T97A 8
T97T/A 4
E138A 1
E138E/A 1
E138E/K 3
E138K 4
E138T/A 1
N155H 6
N155N/H 1
Q148H 3
Q148Q/H 2
Q148R 1
Q148Q/R/K 1
G140G/S 1
G140S 3
L74L/M/V 1
L74L/M 1
L74I 1
E92E/Q 2
S147G 2
E157E/Q 1
V151V/M/I 1
Y143Y/H 1
19.Secondary Outcome
Title Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance
Hide Description The FC in IC50 (50% inhibitory concentration) for DTG relative to wild-type virus was determined for virus isolated at Baseline and at the time of PDVF. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. PDVF is defined as a <0.5 log10 copies/mL decrease in plasma HIV-1 RNA at Day 8 unless the absolute value is <400 copies/mL. PDVF after Day 8 was defined for virological non-response (decrease in plasma HIV-1 RNA of less than 1 log10 copies/mL by Week 16, with subsequent confirmation, unless plasma HIV-1 RNA <400 copies/mL and confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24) and virological rebound (confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL and confirmed plasma HIV-1 RNA levels >1 log10 copies/mL above the nadir value, where nadir is >=400 copies/mL).
Time Frame From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)
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Hide Analysis Population Description
PDVF Phenotypic Resistance Populations. Only participants with Baseline DTG IC50 with PDVF who had paired Baseline and time of virological failure samples were considered for analysis.
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description:
Participants received DTG 50 mg BID.
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: Participants
<1 fold 6
1-<2 fold 16
2-<4 fold 4
4-<8 fold 4
>=8 fold 12
Missing 3
Time Frame On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study treament until the end of treatment visit for each participant (up to Week 180)
Adverse Event Reporting Description On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of investigational product.
 
Arm/Group Title Dolutegravir 50 mg BID
Hide Arm/Group Description Participants received DTG 50 mg BID.
All-Cause Mortality
Dolutegravir 50 mg BID
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Dolutegravir 50 mg BID
Affected / at Risk (%)
Total   46/183 (25.14%) 
Cardiac disorders   
Cardiac failure congestive  1  2/183 (1.09%) 
Angina pectoris  1  1/183 (0.55%) 
Coronary artery disease  1  1/183 (0.55%) 
Gastrointestinal disorders   
Constipation  1  1/183 (0.55%) 
Dysphagia  1  1/183 (0.55%) 
Parotid gland enlargement  1  1/183 (0.55%) 
Diarrhoea  1  2/183 (1.09%) 
Gastritis  1  1/183 (0.55%) 
Haematochezia  1  1/183 (0.55%) 
Rectal haemorrhage  1  1/183 (0.55%) 
Aphthous stomatitis  1  1/183 (0.55%) 
General disorders   
Pyrexia  1  3/183 (1.64%) 
Hepatobiliary disorders   
Cholecystitis acute  1  1/183 (0.55%) 
Cholelithiasis  1  2/183 (1.09%) 
Hepatic cirrhosis  1  1/183 (0.55%) 
Hepatitis acute  1  1/183 (0.55%) 
Hyperbilirubinaemia  1  1/183 (0.55%) 
Bile duct obstruction  1  1/183 (0.55%) 
Drug-induced liver injury  1  1/183 (0.55%) 
Hepatocellular injury  1  1/183 (0.55%) 
Nodular regenerative hyperplasia  1  1/183 (0.55%) 
Immune system disorders   
Immune reconstitution inflammatory syndrome  1  1/183 (0.55%) 
Infections and infestations   
Pneumonia  1  5/183 (2.73%) 
Progressive multifocal leukoencephalopathy  1  2/183 (1.09%) 
Cytomegalovirus infection  1  1/183 (0.55%) 
Cytomegalovirus viraemia  1  1/183 (0.55%) 
Epstein-Barr virus infection  1  1/183 (0.55%) 
Gastroenteritis viral  1  1/183 (0.55%) 
Herpes ophthalmic  1  1/183 (0.55%) 
Herpes zoster  1  1/183 (0.55%) 
Lung infection  1  1/183 (0.55%) 
Oesophageal candidiasis  1  1/183 (0.55%) 
Pneumococcal sepsis  1  1/183 (0.55%) 
Septic shock  1  1/183 (0.55%) 
Streptococcal sepsis  1  1/183 (0.55%) 
Viral infection  1  1/183 (0.55%) 
Eye infection toxoplasmal  1  1/183 (0.55%) 
Gastroenteritis  1  1/183 (0.55%) 
Herpes virus infection  1  1/183 (0.55%) 
Hepatitis B  1  1/183 (0.55%) 
Oral candidiasis  1  1/183 (0.55%) 
Orchitis  1  1/183 (0.55%) 
Investigations   
Alanine aminotransferase increased  1  1/183 (0.55%) 
Metabolism and nutrition disorders   
Dehydration  1  3/183 (1.64%) 
Musculoskeletal and connective tissue disorders   
Tendonitis  1  1/183 (0.55%) 
Joint destruction  1  1/183 (0.55%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Bowen's disease  1  1/183 (0.55%) 
Squamous cell carcinoma  1  2/183 (1.09%) 
Anogenital warts  1  1/183 (0.55%) 
Bile duct cancer  1  1/183 (0.55%) 
Hodgkin's disease recurrent  1  1/183 (0.55%) 
Anal cancer stage I  1  1/183 (0.55%) 
B-cell lymphoma  1  1/183 (0.55%) 
Hodgkin's disease  1  1/183 (0.55%) 
Lip and/or oral cavity cancer  1  1/183 (0.55%) 
Lip and/or oral cavity cancer stage 0  1  1/183 (0.55%) 
Squamous cell carcinoma of the cervix  1  1/183 (0.55%) 
Nervous system disorders   
Cerebrovascular accident  1  1/183 (0.55%) 
Convulsion  1  1/183 (0.55%) 
Nerve compression  1  1/183 (0.55%) 
Syncope  1  1/183 (0.55%) 
Transient ischaemic attack  1  1/183 (0.55%) 
Seizure  1  1/183 (0.55%) 
Psychiatric disorders   
Bipolar disorder  1  1/183 (0.55%) 
Depression  1  1/183 (0.55%) 
Renal and urinary disorders   
Renal failure  1  1/183 (0.55%) 
Acute kidney injury  1  1/183 (0.55%) 
Reproductive system and breast disorders   
Ovarian mass  1  1/183 (0.55%) 
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  2/183 (1.09%) 
Acute respiratory failure  1  1/183 (0.55%) 
Productive cough  1  1/183 (0.55%) 
Pulmonary embolism  1  1/183 (0.55%) 
Lung disorder  1  2/183 (1.09%) 
Bronchopneumopathy  1  1/183 (0.55%) 
Skin and subcutaneous tissue disorders   
Drug eruption  1  1/183 (0.55%) 
Pruritus  1  1/183 (0.55%) 
Rash  1  1/183 (0.55%) 
Rash generalised  1  1/183 (0.55%) 
Vascular disorders   
Hypertensive emergency  1  1/183 (0.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dolutegravir 50 mg BID
Affected / at Risk (%)
Total   143/183 (78.14%) 
Gastrointestinal disorders   
Diarrhoea  1  41/183 (22.40%) 
Nausea  1  26/183 (14.21%) 
Vomiting  1  13/183 (7.10%) 
Abdominal pain upper  1  14/183 (7.65%) 
Constipation  1  12/183 (6.56%) 
General disorders   
Fatigue  1  17/183 (9.29%) 
Pyrexia  1  19/183 (10.38%) 
Asthenia  1  13/183 (7.10%) 
Injection site reaction  1  12/183 (6.56%) 
Infections and infestations   
Bronchitis  1  25/183 (13.66%) 
Upper respiratory tract infection  1  22/183 (12.02%) 
Nasopharyngitis  1  12/183 (6.56%) 
Rhinitis  1  11/183 (6.01%) 
Influenza  1  11/183 (6.01%) 
Sinusitis  1  11/183 (6.01%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  18/183 (9.84%) 
Arthralgia  1  12/183 (6.56%) 
Pain in extremity  1  11/183 (6.01%) 
Nervous system disorders   
Headache  1  24/183 (13.11%) 
Psychiatric disorders   
Insomnia  1  14/183 (7.65%) 
Anxiety  1  10/183 (5.46%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  29/183 (15.85%) 
Oropharyngeal pain  1  10/183 (5.46%) 
Skin and subcutaneous tissue disorders   
Rash  1  17/183 (9.29%) 
Pruritus  1  11/183 (6.01%) 
Vascular disorders   
Hypertension  1  11/183 (6.01%) 
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
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: ViiV Healthcare
Phone: 866-435-7343
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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01328041    
Other Study ID Numbers: 112574
First Submitted: March 31, 2011
First Posted: April 4, 2011
Results First Submitted: August 15, 2013
Results First Posted: July 21, 2014
Last Update Posted: January 7, 2016