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A Dose Ranging Trial of GSK1349572 and 2 NRTI in HIV-1 Infected, Therapy Naive Subjects (ING112276)

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ClinicalTrials.gov Identifier: NCT00951015
Recruitment Status : Completed
First Posted : August 3, 2009
Results First Posted : November 11, 2013
Last Update Posted : January 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: efavirenz
Enrollment 208
Recruitment Details Randomization Phase participants received Dolutegravir (DTG 10, 25 or 50 milligrams[mg]) with Placebo/Efavirenz (EFV) for 96 Weeks . DTG participants who completed 96 Weeks continued or were switched to receive DTG 50 mg in Open label phase until DTG was locally available.
Pre-assignment Details A total of 278 par were screened of which 70 were screen failures and 208 were randomized; 205 received at least one dose of study medication and comprised the Intent-To-Treat exposed (ITT-E) population. 17 participants out of 155 from DTG arm withdrew during Randomization phase and total 138 participants were enrolled in an Open-label phase.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD Open-label DTG 50 mg QD
Hide Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and Abacavir/lamivudine (ABC/3TC) 600 mg/300 mg or tenofovir/emtricitabine (TDF/FTC) 300 mg/200 mg orally once daily (QD) for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg matching placebo and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. All DTG participants were switched to or continued DTG 50 mg with either ABC/3TC orally at 600 mg/300 mg (1 tablet) or TDF/FTC orally QD during the Open label phase
Period Title: Randomization Phase 96 Week
Started 53 51 51 50 0
Completed 48 44 46 40 0
Not Completed 5 7 5 10 0
Reason Not Completed
Adverse Event             1             1             2             5             0
Lack of Efficacy             1             1             0             0             0
Protocol Violation             1             1             1             0             0
Protocol-Defined Stopping Criteria             0             0             0             1             0
Lost to Follow-up             0             3             1             2             0
Withdrawal by Subject             2             1             1             2             0
Period Title: Open-label Phase
Started 0 0 0 0 138
Completed 0 0 0 0 88
Not Completed 0 0 0 0 50
Reason Not Completed
Adverse Event             0             0             0             0             3
Lack of Efficacy             0             0             0             0             1
Protocol Violation             0             0             0             0             12
Lost to Follow-up             0             0             0             0             12
Withdrawal by Subject             0             0             0             0             14
Physician Decision             0             0             0             0             8
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD Total
Hide Arm/Group Description Participants received Dolutegravir (DTG) 10 milligrams (mg), DTG matching placebo, and Abacavir (ABC)/Lamivudine (3TC) 600 mg/300 mg or Tenofovir (TDF)/Emtricitabine (FTC) 300 mg/200 mg orally once daily (QD) for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Total of all reporting groups
Overall Number of Baseline Participants 53 51 51 50 205
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 53 participants 51 participants 51 participants 50 participants 205 participants
34.2  (9.25) 37.0  (9.79) 37.0  (8.89) 40.7  (11.19) 37.2  (10.00)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 51 participants 51 participants 50 participants 205 participants
Female
11
  20.8%
5
   9.8%
6
  11.8%
6
  12.0%
28
  13.7%
Male
42
  79.2%
46
  90.2%
45
  88.2%
44
  88.0%
177
  86.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 53 participants 51 participants 51 participants 50 participants 205 participants
African American/African Heritage (HER) 7 6 8 4 25
American Indian or Alaska Native 1 3 4 2 10
Japanese/East Asian HER/South East Asian HER 0 0 0 1 1
Native Hawaiian or other Pacific Islander 3 0 0 0 3
White 41 42 38 43 164
African American/African HER & White 0 0 1 0 1
Asian & White 1 0 0 0 1
1.Primary Outcome
Title Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16
Hide Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Week 16. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason. Data are reported per the Week 16 report. In later cuts of the data, the Week 16 values may have changed (because of the nature of the TLOVR algorithm).ITT-E Population included all randomized participants who received at least one dose of study medication
Time Frame Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received Dolutegravir (DTG) 10 milligrams (mg), DTG matching placebo, and Abacavir (ABC)/Lamivudine (3TC) 600 mg/300 mg or Tenofovir (TDF)/Emtricitabine (FTC) 300 mg/200 mg orally once daily (QD) for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 51 51 50
Measure Type: Number
Unit of Measure: participants
51 47 46 29
2.Secondary Outcome
Title Viral Change Over the Initial 2 Weeks of Treatment
Hide Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline and Week 2. Viral change is defined as the change in plasma HIV-1 RNA over the initial 2 weeks of treatment, calculated as the value at Week 2 minus the value at Baseline. Only those participants available at the specified time point were analyzed.
Time Frame Baseline and Week 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 50 50 48
Mean (Standard Deviation)
Unit of Measure: Log10 c/mL
-2.387  (0.4595) -2.365  (0.5458) -2.392  (0.4241) -1.930  (0.4312)
3.Secondary Outcome
Title Change From Baseline in HIV-1 RNA at the Indicated Time Points
Hide Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, 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 DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 51 51 50
Mean (Standard Deviation)
Unit of Measure: Log10 c/mL
Week 1, n=53, 50, 48, 50 Number Analyzed 53 participants 50 participants 48 participants 50 participants
-1.815  (0.3999) -1.773  (0.4650) -1.738  (0.3840) -1.562  (0.4158)
Week 2, n=53, 50, 50, 48 Number Analyzed 53 participants 50 participants 50 participants 48 participants
-2.387  (0.4595) -2.365  (0.5458) -2.392  (0.4241) -1.930  (0.4312)
Week 4, n=53, 50, 50, 45 Number Analyzed 53 participants 50 participants 50 participants 45 participants
-2.629  (0.5863) -2.583  (0.6337) -2.713  (0.5471) -2.162  (0.5400)
Week 8, n=52, 50, 49, 45 Number Analyzed 52 participants 50 participants 49 participants 45 participants
-2.657  (0.6980) -2.666  (0.6667) -2.848  (0.6556) -2.450  (0.5989)
Week 12, n=53, 49, 49, 45 Number Analyzed 53 participants 49 participants 49 participants 45 participants
-2.685  (0.6831) -2.671  (0.6850) -2.860  (0.6772) -2.603  (0.5869)
Week 16, n=52, 49, 49, 45 Number Analyzed 52 participants 49 participants 49 participants 45 participants
-2.718  (0.6593) -2.668  (0.6826) -2.859  (0.6876) -2.698  (0.6715)
Week 20, n=52, 48, 49, 44 Number Analyzed 52 participants 48 participants 49 participants 44 participants
-2.701  (0.6423) -2.662  (0.6908) -2.869  (0.6896) -2.745  (0.6602)
Week 24, n=52, 49, 48, 45 Number Analyzed 52 participants 49 participants 48 participants 45 participants
-2.700  (0.6261) -2.657  (0.6969) -2.853  (0.6889) -2.773  (0.7026)
Week 32, n=52, 49, 47, 45 Number Analyzed 52 participants 49 participants 47 participants 45 participants
-2.717  (0.6588) -2.658  (0.6991) -2.855  (0.6963) -2.772  (0.7021)
Week 40, n=51, 48, 47, 44 Number Analyzed 51 participants 48 participants 47 participants 44 participants
-2.647  (0.7039) -2.665  (0.7051) -2.855  (0.6934) -2.795  (0.7169)
Week 48, n=51, 48, 48, 45 Number Analyzed 51 participants 48 participants 48 participants 45 participants
-2.723  (0.6519) -2.667  (0.6934) -2.850  (0.6849) -2.711  (0.7765)
Week 60, n=50, 48, 48, 44 Number Analyzed 50 participants 48 participants 48 participants 44 participants
-2.741  (0.6444) -2.675  (0.7012) -2.825  (0.7458) -2.765  (0.7035)
Week 72, n=51, 47, 48, 44 Number Analyzed 51 participants 47 participants 48 participants 44 participants
-2.742  (0.6453) -2.622  (0.8052) -2.860  (0.6930) -2.757  (0.7094)
Week 84, n=51, 47, 47, 43 Number Analyzed 51 participants 47 participants 47 participants 43 participants
-2.725  (0.6506) -2.670  (0.7064) -2.855  (0.6923) -2.743  (0.7321)
Week 96, n=48, 44, 46, 39 Number Analyzed 48 participants 44 participants 46 participants 39 participants
-2.728  (0.6494) -2.680  (0.7116) -2.854  (0.7061) -2.807  (0.7238)
4.Secondary Outcome
Title Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points
Hide Description Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, 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.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 51 51 50
Median (Inter-Quartile Range)
Unit of Measure: Cells per cubic millimeter
Week 1, n=53, 50, 48, 50 Number Analyzed 53 participants 50 participants 48 participants 50 participants
85.0
(18.0 to 134.0)
94.5
(40.0 to 160.0)
75.5
(18.5 to 129.5)
42.5
(-23.0 to 111.0)
Week 2, n=53, 50, 50, 47 Number Analyzed 53 participants 50 participants 50 participants 47 participants
75.0
(37.0 to 124.0)
79.0
(27.0 to 138.0)
99.5
(53.0 to 160.0)
55.0
(-10.0 to 132.0)
Week 4, n=53, 50, 50, 45 Number Analyzed 53 participants 50 participants 50 participants 45 participants
75.0
(34.0 to 151.0)
89.0
(36.0 to 165.0)
110.0
(46.0 to 170.0)
89.0
(30.0 to 165.0)
Week 8, n=52, 50, 49, 44 Number Analyzed 52 participants 50 participants 49 participants 44 participants
118.5
(65.5 to 210.5)
156.5
(93.0 to 226.0)
129.0
(105.0 to 201.0)
104.5
(34.5 to 240.5)
Week 12, n=53, 48, 48, 45 Number Analyzed 53 participants 48 participants 48 participants 45 participants
139.0
(96.0 to 284.0)
137.5
(61.0 to 250.0)
171.5
(107.5 to 269.0)
127.0
(58.0 to 186.0)
Week 16, n=52, 49, 49, 44 Number Analyzed 52 participants 49 participants 49 participants 44 participants
153.0
(95.0 to 276.0)
176.0
(86.0 to 227.0)
160.0
(94.0 to 227.0)
115.5
(65.5 to 226.0)
Week 20, n=52, 48, 49, 44 Number Analyzed 52 participants 48 participants 49 participants 44 participants
163.5
(79.5 to 288.5)
200.0
(103.0 to 316.5)
139.0
(64.0 to 238.0)
136.0
(54.5 to 215.5)
Week 24, n=51, 49, 47, 44 Number Analyzed 51 participants 49 participants 47 participants 44 participants
159.0
(97.0 to 233.0)
206.0
(102.0 to 289.0)
167.0
(125.0 to 268.0)
109.5
(66.0 to 229.0)
Week 32, n=50, 48, 47, 44 Number Analyzed 50 participants 48 participants 47 participants 44 participants
221.5
(94.0 to 300.0)
195.5
(109.0 to 294.0)
203.0
(125.0 to 282.0)
146.5
(82.5 to 223.5)
Week 40, n=50, 48, 47, 44 Number Analyzed 50 participants 48 participants 47 participants 44 participants
205.0
(136.0 to 364.0)
204.5
(157.5 to 346.5)
224.0
(123.0 to 322.0)
171.5
(123.0 to 268.0)
Week 48, n=51, 47, 47, 45 Number Analyzed 51 participants 47 participants 47 participants 45 participants
204.0
(127.0 to 384.0)
249.0
(143.0 to 416.0)
223.0
(141.0 to 292.0)
174.0
(91.0 to 292.0)
Week 60, n=51, 48, 47, 43 Number Analyzed 51 participants 48 participants 47 participants 43 participants
265.0
(173.0 to 365.0)
278.0
(198.5 to 369.5)
229.0
(166.0 to 306.0)
221.0
(153.0 to 355.0)
Week 72, n=51, 47, 48, 44 Number Analyzed 51 participants 47 participants 48 participants 44 participants
236.0
(177.0 to 351.0)
285.0
(186.0 to 427.0)
220.0
(146.0 to 373.0)
195.0
(144.0 to 334.5)
Week 84, n=51, 47, 46, 42 Number Analyzed 51 participants 47 participants 46 participants 42 participants
292.0
(222.0 to 408.0)
313.0
(244.0 to 366.0)
280.0
(197.0 to 379.0)
296.5
(187.0 to 400.0)
Week 96, n=48, 44, 46, 39 Number Analyzed 48 participants 44 participants 46 participants 39 participants
335.0
(253.5 to 478.5)
391.5
(243.0 to 527.0)
326.0
(236.0 to 451.0)
301.0
(204.0 to 445.0)
5.Secondary Outcome
Title Number of Participants With New HIV-associated Conditions of the Indicated Class
Hide Description HIV-associated conditions were 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 acquired immunodeficiency syndrome (AIDS) surveillance case definition.
Time Frame From Baseline up to Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 51 51 50
Measure Type: Number
Unit of Measure: Participants
Category B 2 0 1 1
Category C 0 0 1 0
Death 1 0 0 0
6.Secondary Outcome
Title Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death)
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: CAT A at Baseline (BS) to CAT B event (EV), CAT A at BS to a CAT C EV; CAT B at BS to a CAT C EV; CAT C at BS to a new CAT C EV; or CAT A, B, or C at BS to death.
Time Frame From Baseline up to Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 51 51 50
Measure Type: Number
Unit of Measure: Participants
CAT A at Baseline to a CAT C event 0 0 0 0
CAT B at Baseline to a CAT C event 0 0 1 0
CAT C at Baseline to a new CAT C event 0 0 0 0
CAT A, B, or C at Baseline to death 1 0 0 0
7.Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA <50 c/mL
Hide Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 51 51 50
Measure Type: Number
Unit of Measure: Participants
Baseline 0 0 0 0
Week 1 6 4 4 3
Week 2 22 19 11 6
Week 4 37 35 31 9
Week 8 46 45 43 18
Week 12 50 46 45 25
Week 16 51 46 47 29
Week 20 51 47 47 38
Week 24 51 46 47 41
Week 32 50 45 46 43
Week 40 49 45 46 42
Week 48 48 45 46 40
Week 60 48 44 46 41
Week 72 48 44 45 40
Week 84 47 43 46 38
Week 96 42 40 45 36
8.Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA <400 c/mL
Hide Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<400 c/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
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ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 51 51 50
Measure Type: Number
Unit of Measure: Participants
Baseline 0 0 0 0
Week 1 25 20 16 15
Week 2 45 45 41 23
Week 4 52 49 48 32
Week 8 52 49 49 41
Week 12 52 49 49 45
Week 16 52 48 49 45
Week 20 52 48 49 45
Week 24 52 47 48 45
Week 32 52 47 48 45
Week 40 50 47 48 45
Week 48 50 47 48 44
Week 60 50 46 48 44
Week 72 50 46 47 43
Week 84 50 45 47 42
Week 96 46 43 46 39
9.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE)
Hide Description An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (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; or is a congenital anomaly/birth defect. All clinically suspected cases of hypersensitivity reaction to abacavir in participants receiving abacavir/lamivudine were reported as SAEs. Medical or scientific judgment was to have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occuring at a frequency threshold >=3%) and SAEs.
Time Frame From Baseline up to Week 96/Early Withdrawal
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Safety Population:All participants who received at least one dose of the study medication
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 51 51 50
Measure Type: Number
Unit of Measure: Participants
Any AE 50 46 46 46
Any SAE 5 5 7 7
10.Secondary Outcome
Title Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities
Hide Description Blood samples were collected for the measurement of clinical chemistry and hematology parameters. Toxicities were graded for severity according to the Division of AIDS (DAIDS) toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).
Time Frame From Baseline up to Week 96/Early Withdrawal
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Hide Analysis Population Description
Safety Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 53 51 51 50
Measure Type: Number
Unit of Measure: Participants
Alanine amino transferase 7 11 3 19
Cholesterol 18 16 13 24
Creatinine kinase 17 6 7 5
Lipase 11 13 11 9
Triglycerides 0 1 2 1
Alkaline phosphatase 1 0 1 10
Amylase 2 3 1 4
Aspartate amino transferase 12 8 6 9
Carbon dioxide content/bicarbonate 28 24 23 30
Creatinine 0 4 0 0
Hypercalcemia 0 0 0 1
Hyperglycaemia 16 15 17 17
Hyperkalemia 0 0 1 1
Hypernatremia 1 1 1 0
Hypocalcemia 4 5 5 8
Hypoglycaemia 3 3 5 4
Hypokalemia 4 1 3 3
Hyponatremia 6 12 7 13
Low-density lipoprotein cholesterol 14 15 11 20
Magnesium 7 6 5 4
Phosphate, inorganic 9 15 14 11
Total bilirubin 3 4 3 0
Activated partial thromboplastin time 7 12 6 5
Hemoglobin 0 1 0 1
International normalized ratio 6 9 6 5
Platelet count 1 4 1 1
Prothrombin time 7 8 7 4
Total neutrophils 9 7 6 10
White blood cell count 1 1 1 1
11.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 For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure 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 4, 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 without evidence of prior suppression to <400copies/mL 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 >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.On-treatment Genotypic Resistance Population: all participants in the ITT-E Population with available on-treatment genotypic data, excluding participants who were not protocol-defined virologic failures.
Time Frame From Baseline up to Week 96/Early Withdrawal
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On-treatment Genotypic Resistance Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 2 1 0 1
Measure Type: Number
Unit of Measure: Participants
A23A/V 1 0 0
S255N 1 0 0
12.Secondary Outcome
Title Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
Hide Description For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure 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 4, 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 without evidence of prior suppression to <400copies/mL 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 >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.
Time Frame From Baseline up to Week 96/Early Withdrawal
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Hide Analysis Population Description
On-treatment Genotypic Resistance Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 2 1 0 1
Measure Type: Number
Unit of Measure: Participants
1 0 0
13.Secondary Outcome
Title Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at 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. Fold increase in DTG FC at the time of PDVF was derived as the PDVF FC/Baseline FC ratio. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, 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 without evidence of prior suppression to <400copies/mL 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 >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.On-treatment Phenotypic Resistance Population: all participants in the ITT-E Population with available on-treatment phenotypic data
Time Frame From Baseline up to Week 96/Early Withdrawal
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On-treatment Phenotypic Resistance Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 2 1 0 0
Measure Type: Number
Unit of Measure: Participants
<1 fold 0 1
1-<2 fold 2 0
2-<4 fold 0 0
4-<8 fold 0 0
>=8 fold 0 0
14.Secondary Outcome
Title Plasma DTG Concentration
Hide Description Blood samples for the determination of plasma DTG concentration were collected from the participants randomized to receive DTG, at the following time points: pre-dose and 2-4 hours post-dose at Weeks 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. The Pharmacokinetic (PK) Summary Population is comprised of all participants who received DTG and underwent intensive PK sampling or limited PK sampling during the study and provided evaluable DTG PK parameters. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, 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 PK Summary Population.
Time Frame Week 2, Week 12, and Week 24
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Hide Analysis Population Description
PK Summary Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 48 46 46 0
Mean (Standard Deviation)
Unit of Measure: Micrograms per milliliter (µg/mL)
Week 2, Pre-dose, n=46, 44, 43, 0 Number Analyzed 46 participants 44 participants 43 participants 0 participants
0.3580  (0.18321) 0.6779  (0.44085) 1.4044  (0.88041)
Week 2, 2-4 hours post-dose, n=31, 29, 29, 0 Number Analyzed 31 participants 29 participants 29 participants 0 participants
1.0121  (0.28125) 1.9716  (0.71890) 3.8414  (1.87405)
Week 12, Pre-dose, n= 46, 45, 44, 0 Number Analyzed 46 participants 45 participants 44 participants 0 participants
0.3648  (0.16791) 0.5759  (0.32645) 1.4169  (1.00152)
Week 12, 2-4 hours post-dose, n=48, 45, 45, 0 Number Analyzed 48 participants 45 participants 45 participants 0 participants
1.0374  (0.27517) 1.7907  (0.70953) 3.6056  (1.33862)
Week 24, Pre-dose, n=45, 44, 44, 0 Number Analyzed 45 participants 44 participants 44 participants 0 participants
0.3766  (0.23399) 0.6636  (0.50767) 1.4534  (0.94283)
Week 24, 2-4 hours post-dose, n=45, 45, 45, 0 Number Analyzed 45 participants 45 participants 45 participants 0 participants
1.0113  (0.34083) 1.9021  (0.79430) 3.5397  (1.36538)
15.Secondary Outcome
Title AUC(0-tau) of DTG
Hide Description The area under the time concentration curve over the dosing interval (AUC[0-tau]) of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed.
Time Frame Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
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Hide Analysis Population Description
PK Summary Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 15 15 15 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*µg/mL
16.0
(40%)
23.1
(48%)
48.1
(40%)
16.Secondary Outcome
Title Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG
Hide Description The Cmax, Cmax, and Ctau of DTG were determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
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Hide Analysis Population Description
PK Summary Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title DTG 10 mg OD DTG 25 mg OD DTG 50 mg OD EFV 600 mg OD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.
Overall Number of Participants Analyzed 15 15 15 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg/mL
Cmax
1.10
(37%)
1.71
(43%)
3.40
(27%)
Cmin
0.33
(64%)
0.44
(68%)
0.94
(74%)
Ctau
0.37
(55%)
0.45
(71%)
1.05
(72%)
17.Secondary Outcome
Title Pre-dose Concentration (C0) and C0 Avg of DTG
Hide Description The plasma DTG C0 of DTG was determined using limited/sparse PK sampling at Week 2, Week 12, and Week 24. C0 avg was calculated at Week 24 as the mean of the C0 of DTG at Week 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, 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 PK Summary Population.
Time Frame Week 2, Week 12, and Week 24
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Hide Analysis Population Description
PK Summary Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg QD.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 49 46 46 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Microgram per milliliter (µg/mL)
C0, Week 2, n=46, 44, 43, 0 Number Analyzed 46 participants 44 participants 43 participants 0 participants
0.31
(58%)
0.57
(62%)
1.20
(61%)
C0, Week 12, n=46, 45, 44, 0 Number Analyzed 46 participants 45 participants 44 participants 0 participants
0.33
(49%)
0.47
(77%)
1.13
(95%)
C0, Week 24, n=45, 44, 44, 0 Number Analyzed 45 participants 44 participants 44 participants 0 participants
0.33
(67%)
0.57
(74%)
1.20
(74%)
C0 avg, n=48, 46, 46, 0 Number Analyzed 48 participants 46 participants 46 participants 0 participants
0.34
(49%)
0.56
(61%)
1.25
(55%)
18.Secondary Outcome
Title Time to Maximal Drug Concentration (Tmax) of DTG
Hide Description Tmax of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2
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Hide Analysis Population Description
PK Summary Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 15 15 15 0
Median (Full Range)
Unit of Measure: Hours
2.0
(2.0 to 4.0)
2.0
(2.0 to 8.0)
2.0
(1.9 to 4.0)
19.Secondary Outcome
Title Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters
Hide Description Relationships between Week 2 plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], and Ctau [concentration at the end of the dosing interval]) and the change from Baseline in plasma HIV-1 RNA at Week 2 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson’s correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between plasma HIV-1 RNA and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. PK/Pharmacodynamic (PD) Analysis Population: all participants with available PD measures (e.g., safety and/or efficacy data) and with evaluable DTG plasma concentration data considered suitable for investigation of relationship with the PD measures
Time Frame Week 2
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Hide Analysis Population Description
PK/PD Analysis Population.Only those participants available at the specified time points were analyzed.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD Overall DTG
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
All participants who received DTG in any DTG treatment group (DTG 10 mg QD, DTG 25 mg QD, and DTG 50 mg QD)
Overall Number of Participants Analyzed 15 15 15 0 45
Measure Type: Number
Unit of Measure: Pearson's correlation coefficient
AUC(0-tau) 0.426 -0.018 -0.258 -0.086
Cmax 0.452 -0.051 -0.150 -0.055
Ctau 0.273 -0.100 -0.263 -0.129
20.Secondary Outcome
Title Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters
Hide Description Relationships between plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], C0avg [average pre-dose concentration], and Ctau [concentration at the end of the dosing interval]) and the change from Baseline in CD4+ cell counts at Week 96 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson’s correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between CD4+ cell counts and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association.Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)
Time Frame Week 96
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Hide Analysis Population Description
PK/PD Analysis Population.
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD Overall DTG
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
All participants who received DTG in any DTG treatment group (DTG 10 mg QD, DTG 25 mg QD, and DTG 50 mg QD)
Overall Number of Participants Analyzed 50 46 46 0 142
Measure Type: Number
Unit of Measure: Pearson's correlation coefficient
AUC(0-tau), n=13, 14, 15, 0 Number Analyzed 13 participants 14 participants 15 participants 0 participants 142 participants
-0.100 0.379 0.008 -0.005
Cmax, n=13, 14, 15, 0 Number Analyzed 13 participants 14 participants 15 participants 0 participants 142 participants
-0.047 0.332 0.234 0.037
C0avg, n=43, 40, 42, 0 Number Analyzed 43 participants 40 participants 42 participants 0 participants 142 participants
-0.009 -0.013 0.206 -0.011
Ctau, n=13, 14, 15, 0 Number Analyzed 13 participants 14 participants 15 participants 0 participants 142 participants
-0.289 0.299 -0.074 -0.055
21.Secondary Outcome
Title Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters
Hide Description Relationships between log-transformed plasma DTG PK parameters (AUC[0-tau], Cmax, C0, C0avg, Ctau, and Cmin) and safety parameters (AE occurrence, maximum AE intensity, alanine aminotransferase [ALT], change from Baseline [CFB] in ALT, total bilirubin, CFB in total bilirubin, creatine kinase, CFB in creatine kinase, triglycerides, CFB in triglycerides, lipase, CFB in lipase, total cholesterol [TC], CFB in TC) was assessed using Pearson’s correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between safety parameters and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. The presence of >=1 AE was used for AE occurrence. The most severe AE grade/intensity was used for maximum AE intensity. Maximum laboratory values per participant were used for safety parameters. CFB was calculated as the post-Baseline value minus the value at Baseline.
Time Frame Week 96
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Hide Analysis Population Description
PK/PD Analysis Population.Only those participants available at the specified time points were analyzed
Arm/Group Title Overall DTG
Hide Arm/Group Description:
All participants who received DTG in any DTG treatment group (DTG 10 mg QD, DTG 25 mg QD, and DTG 50 mg QD)
Overall Number of Participants Analyzed 142
Measure Type: Number
Unit of Measure: Pearson's correlation coefficient
AUC(0-tau) versus AE occurrence, n=45 Number Analyzed 45 participants
0.114
AUC(0-tau) versus maximum AE intensity, n=45 Number Analyzed 45 participants
0.171
AUC(0-tau) versus ALT, n=45 Number Analyzed 45 participants
-0.196
AUC(0-tau) versus CFB in ALT, n=45 Number Analyzed 45 participants
-0.201
AUC(0-tau) versus total bilirubin, n=45 Number Analyzed 45 participants
0.364
AUC(0-tau) versus CFB in total bilirubin, n=45 Number Analyzed 45 participants
0.147
AUC(0-tau) versus creatine kinase, n=45 Number Analyzed 45 participants
-0.168
AUC(0-tau) versus CFB in creatine kinase, n=45 Number Analyzed 45 participants
-0.145
AUC(0-tau) vs Triglycerides, n=45 Number Analyzed 45 participants
0.104
AUC(0-tau) versus CFB in triglycerides, n=45 Number Analyzed 45 participants
0.216
AUC(0-tau) versus lipase, n=45 Number Analyzed 45 participants
-0.066
AUC(0-tau) versus CFB in lipase, n=45 Number Analyzed 45 participants
0.092
AUC(0-tau) versus total cholesterol, n=45 Number Analyzed 45 participants
-0.097
AUC(0-tau) versus CFB in total cholesterol, n=45 Number Analyzed 45 participants
-0.153
Cmax versus AE occurrence, n=45 Number Analyzed 45 participants
0.061
Cmax versus maximum AE intensity, n=45 Number Analyzed 45 participants
0.110
Cmax versus ALT, n=45 Number Analyzed 45 participants
-0.135
Cmax versus CFB in ALT, n=45 Number Analyzed 45 participants
-0.135
Cmax versus total bilirubin, n=45 Number Analyzed 45 participants
0.265
Cmax versus CFB in total bilirubin, n=45 Number Analyzed 45 participants
0.033
Cmax versus creatine kinase, n=45 Number Analyzed 45 participants
-0.188
Cmax versus CFB in creatine kinase, n=45 Number Analyzed 45 participants
-0.161
Cmax versus triglycerides, n=45 Number Analyzed 45 participants
0.134
Cmax versus CFB in triglycerides, n=45 Number Analyzed 45 participants
0.244
Cmax versus lipase, n=45 Number Analyzed 45 participants
-0.034
Cmax versus CFB in lipase, n=45 Number Analyzed 45 participants
0.115
Cmax versus total cholesterol, n=45 Number Analyzed 45 participants
-0.101
Cmax versus CFB in total cholesterol, n=45 Number Analyzed 45 participants
-0.192
C0 versus AE occurrence, n=133 Number Analyzed 133 participants
-0.080
C0 versus maximum AE intensity, n=133 Number Analyzed 133 participants
-0.003
C0 versus ALT, n=133 Number Analyzed 133 participants
-0.196
C0 versus CFB in ALT, n=133 Number Analyzed 133 participants
-0.237
C0 versus total bilirubin, n=133 Number Analyzed 133 participants
0.298
C0 versus CFB in total bilirubin, n=133 Number Analyzed 133 participants
0.120
C0 versus creatine kinase, n=133 Number Analyzed 133 participants
-0.094
C0 versus CFB in creatine kinase, n=133 Number Analyzed 133 participants
-0.093
C0 versus triglycerides, n=133 Number Analyzed 133 participants
-0.058
C0 versus CFB in triglycerides, n=133 Number Analyzed 133 participants
-0.012
C0 versus lipase, n=133 Number Analyzed 133 participants
-0.187
C0 versus CFB in lipase, n=133 Number Analyzed 133 participants
-0.137
C0 versus total cholesterol, n=133 Number Analyzed 133 participants
-0.179
C0 versus CFB in total cholesterol, n=133 Number Analyzed 133 participants
-0.125
C0avg versus AE occurrence, n=140 Number Analyzed 140 participants
-0.028
C0avg versus maximum AE intensity, n=140 Number Analyzed 140 participants
0.036
C0avg versus ALT, n=140 Number Analyzed 140 participants
-0.166
C0avg versus CFB in ALT, n=140 Number Analyzed 140 participants
-0.177
C0avg versus total bilirubin, n=140 Number Analyzed 140 participants
0.319
C0avg versus CFB in total bilirubin, n=140 Number Analyzed 140 participants
0.109
C0avg versus creatine kinase, n=140 Number Analyzed 140 participants
-0.114
C0avg versus CFB in creatine kinase, n=140 Number Analyzed 140 participants
-0.110
C0avg versus triglycerides, n=140 Number Analyzed 140 participants
0.057
C0avg versus CFB in triglycerides, n=140 Number Analyzed 140 participants
0.092
C0avg versus lipase, n=140 Number Analyzed 140 participants
-0.164
C0avg versus CFB in lipase, n=140 Number Analyzed 140 participants
-0.120
C0avg versus total cholesterol, n=140 Number Analyzed 140 participants
-0.170
C0avg versus CFB in total cholesterol, n=140 Number Analyzed 140 participants
-0.083
Ctau versus AE occurrence, n=45 Number Analyzed 45 participants
0.190
Ctau versus maximum AE intensity, n=45 Number Analyzed 45 participants
0.205
Ctau versus ALT, n=45 Number Analyzed 45 participants
-0.281
Ctau versus CFB in ALT, n=45 Number Analyzed 45 participants
-0.285
Ctau versus total bilirubin, n=45 Number Analyzed 45 participants
0.446
Ctau versus CFB in total bilirubin, n=45 Number Analyzed 45 participants
0.237
Ctau versus creatine kinase, n=45 Number Analyzed 45 participants
-0.143
Ctau versus CFB in creatine kinase, n=45 Number Analyzed 45 participants
-0.125
Ctau versus triglycerides, n=45 Number Analyzed 45 participants
0.061
Ctau versus CFB in triglycerides, n=45 Number Analyzed 45 participants
0.172
Ctau versus lipase, n=45 Number Analyzed 45 participants
-0.131
Ctau versus CFB in lipase, n=45 Number Analyzed 45 participants
0.056
Ctau versus total cholesterol, n=45 Number Analyzed 45 participants
-0.039
Ctau versus CFB in total cholesterol, n=45 Number Analyzed 45 participants
-0.108
Cmin versus AE occurrence, n=45 Number Analyzed 45 participants
0.156
Cmin versus maximum AE intensity, n=45 Number Analyzed 45 participants
0.193
Cmin versus ALT, n=45 Number Analyzed 45 participants
-0.236
Cmin versus CFB in ALT, n=45 Number Analyzed 45 participants
-0.253
Cmin versus total bilirubin, n=45 Number Analyzed 45 participants
0.430
Cmin versus CFB in total bilirubin, n=45 Number Analyzed 45 participants
0.171
Cmin versus creatine kinase, n=45 Number Analyzed 45 participants
-0.132
Cmin versus CFB in creatine kinase, n=45 Number Analyzed 45 participants
-0.124
Cmin versus triglycerides, n=45 Number Analyzed 45 participants
-0.042
Cmin versus CFB in triglycerides, n=45 Number Analyzed 45 participants
0.057
Cmin versus lipase, n=45 Number Analyzed 45 participants
-0.135
Cmin versus CFB in lipase, n=45 Number Analyzed 45 participants
0.032
Cmin versus total cholesterol, n=45 Number Analyzed 45 participants
-0.194
Cmin versus CFB in total cholesterol, n=45 Number Analyzed 45 participants
-0.208
22.Secondary Outcome
Title Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters
Hide Description Logistic regressions were performed to examine the correlation between plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], Ctau [concentration at the end of the dosing interval], and C0avg [average pre-dose concentration]) on log scales and the presence of gastrointestinal system organ class AEs (abdominal pain, diarrhea, nausea, and vomiting) at Week 96. Data are presented as estimates from logistic regression, which is a measure of the association between AEs of special interest and plasma DTG PK parameters. A value of 0 indicates no statistical association; a large absolute value of the estimate indicates higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Results are presented for participants in any DTG group (overall DTG).Only those participants available at the specified time points were analyzed represented by n=X in the category titles
Time Frame Week 96
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Hide Analysis Population Description
PK/PD Analysis Population.
Arm/Group Title Overall DTG
Hide Arm/Group Description:
All participants who received DTG in any DTG treatment group (DTG 10 mg OD, DTG 25 mg OD, and DTG 50 mg OD).
Overall Number of Participants Analyzed 142
Measure Type: Number
Unit of Measure: estimated effect
Abdominal pain versus AUC(0-tau), n=45 Number Analyzed 45 participants
-2.49
Abdominal pain versus Cmax, n=45 Number Analyzed 45 participants
-2.98
Abdominal pain versus Ctau, n=45 Number Analyzed 45 participants
-1.72
Abdominal pain versus C0avg, n=140 Number Analyzed 140 participants
-0.41
Diarrhoea versus AUC(0-tau), n=45 Number Analyzed 45 participants
-0.62
Diarrhoea versus Cmax, n=45 Number Analyzed 45 participants
-0.98
Diarrhoea versus Ctau, n=45 Number Analyzed 45 participants
-0.29
Diarrhoea versus C0avg, n=140 Number Analyzed 140 participants
0.13
Nausea versus AUC(0-tau), n=45 Number Analyzed 45 participants
-0.31
Nausea versus Cmax, n=45 Number Analyzed 45 participants
-0.72
Nausea versus Ctau, n=45 Number Analyzed 45 participants
0.03
Nausea versus C0avg, n=140 Number Analyzed 140 participants
-0.32
Vomiting versus AUC(0-tau), n=45 Number Analyzed 45 participants
-1.29
Vomiting versus Cmax, n=45 Number Analyzed 45 participants
-1.61
Vomiting versus Ctau, n=45 Number Analyzed 45 participants
-1.15
Vomiting versus C0avg, n=140 Number Analyzed 140 participants
-0.89
23.Other Pre-specified Outcome
Title Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points
Hide Description Change from Baseline in CD8+ cell count data are not available; CD8+ data are only listed on a per-participant basis and were not summarized.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96
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Hide Analysis Population Description
ITT-E Population
Arm/Group Title DTG 10 mg QD DTG 25 mg QD DTG 50 mg QD EFV 600 mg QD
Hide Arm/Group Description:
Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Serious adverse events (SAEs) and non-serious AEs were collected in the time period from Baseline up to end of study.
Adverse Event Reporting Description SAEs and AEs were collected in members of Safety Population, comprised of all participants who received at least one dose of study medication.
 
Arm/Group Title DTG 10mg QD DTG 25mg QD DTG 50mg QD EFV 600mg Open-label DTG 50 mg QD
Hide Arm/Group Description Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks. All DTG participants were switched to or continued DTG 50 mg with either ABC/3TC orally at 600 mg/300 mg (1 tablet) or TDF/FTC orally QD during the Open label phase
All-Cause Mortality
DTG 10mg QD DTG 25mg QD DTG 50mg QD EFV 600mg Open-label DTG 50 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/53 (3.77%)      0/51 (0.00%)      0/51 (0.00%)      0/50 (0.00%)      2/138 (1.45%)    
Show Serious Adverse Events Hide Serious Adverse Events
DTG 10mg QD DTG 25mg QD DTG 50mg QD EFV 600mg Open-label DTG 50 mg QD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/53 (11.32%)      4/51 (7.84%)      7/51 (13.73%)      7/50 (14.00%)      16/138 (11.59%)    
Cardiac disorders           
Acute myocardial infarction  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Myocardial infarction  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Gastrointestinal disorders           
Constipation  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Flatulence  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Inguinal hernia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Mallory-Weiss syndrome  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Nausea  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Upper gastrointestinal haemorrhage  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
General disorders           
Pyrexia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Systemic inflammatory response syndrome  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Hepatobiliary disorders           
Cholelithiasis  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Infections and infestations           
Pneumonia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 1/138 (0.72%)  1
Abscess  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Appendicitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Bronchitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Diverticulitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Epididymitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Gastroenteritis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Herpes zoster  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Meningitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Neurosyphilis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Pneumococcal sepsis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Pneumonia pneumococcal  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Primary syphilis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Pyelonephritis acute  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Injury, poisoning and procedural complications           
Wrist fracture  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 1/138 (0.72%)  1
Foot fracture  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  2 0/50 (0.00%)  0 0/138 (0.00%)  0
Humerus fracture  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Injury  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Joint dislocation  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Multiple injuries  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Road traffic accident  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Spinal compression fracture  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Metabolism and nutrition disorders           
Lipomatosis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Obesity  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Musculoskeletal and connective tissue disorders           
Back pain  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  3
Osteoarthritis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  3
Tendonitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Burkitt's lymphoma  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Nervous system disorders           
Headache  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Hydrocephalus  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Seizure  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Product Issues           
Device malfunction  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 1/138 (0.72%)  1
Psychiatric disorders           
Anxiety  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Depression  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Suicide attempt  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Reproductive system and breast disorders           
Dysmenorrhoea  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Vascular disorders           
Phlebitis  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
DTG 10mg QD DTG 25mg QD DTG 50mg QD EFV 600mg Open-label DTG 50 mg QD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   49/53 (92.45%)      46/51 (90.20%)      45/51 (88.24%)      46/50 (92.00%)      112/138 (81.16%)    
Blood and lymphatic system disorders           
Lymphadenopathy  1  2/53 (3.77%)  2 3/51 (5.88%)  3 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Neutropenia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 1/138 (0.72%)  1
Iron deficiency anaemia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Lymphadenitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Cardiac disorders           
Sinus tachycardia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 1/50 (2.00%)  1 0/138 (0.00%)  0
Tachycardia  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Aortic valve incompetence  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Arrhythmia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Bradycardia  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Cardiomegaly  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Palpitations  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Ear and labyrinth disorders           
Vertigo  1  2/53 (3.77%)  2 1/51 (1.96%)  1 2/51 (3.92%)  2 2/50 (4.00%)  2 0/138 (0.00%)  0
Tinnitus  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 2/138 (1.45%)  2
Ear pain  1  0/53 (0.00%)  0 2/51 (3.92%)  2 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Hypoacusis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 2/50 (4.00%)  2 0/138 (0.00%)  0
Cerumen impaction  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Ear congestion  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Ear pruritus  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Presbyacusis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Endocrine disorders           
Hypogonadism  1  2/53 (3.77%)  2 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Hypothyroidism  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Goitre  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Eye disorders           
Astigmatism  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Chalazion  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Dark circles under eyes  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Myopia  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Vision blurred  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Visual acuity reduced  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Vitreous floaters  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Gastrointestinal disorders           
Diarrhoea  1  6/53 (11.32%)  6 9/51 (17.65%)  10 7/51 (13.73%)  8 5/50 (10.00%)  7 12/138 (8.70%)  14
Nausea  1  10/53 (18.87%)  10 8/51 (15.69%)  9 6/51 (11.76%)  6 7/50 (14.00%)  7 2/138 (1.45%)  2
Haemorrhoids  1  0/53 (0.00%)  0 0/51 (0.00%)  0 2/51 (3.92%)  2 2/50 (4.00%)  2 8/138 (5.80%)  10
Abdominal pain  1  3/53 (5.66%)  3 1/51 (1.96%)  1 2/51 (3.92%)  2 1/50 (2.00%)  1 3/138 (2.17%)  3
Dyspepsia  1  1/53 (1.89%)  1 2/51 (3.92%)  3 2/51 (3.92%)  2 2/50 (4.00%)  2 3/138 (2.17%)  3
Abdominal pain upper  1  4/53 (7.55%)  5 3/51 (5.88%)  3 1/51 (1.96%)  1 1/50 (2.00%)  1 0/138 (0.00%)  0
Gastrooesophageal reflux disease  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 2/50 (4.00%)  2 5/138 (3.62%)  5
Vomiting  1  3/53 (5.66%)  3 3/51 (5.88%)  3 0/51 (0.00%)  0 1/50 (2.00%)  1 1/138 (0.72%)  1
Toothache  1  2/53 (3.77%)  2 2/51 (3.92%)  2 1/51 (1.96%)  2 1/50 (2.00%)  1 1/138 (0.72%)  2
Gastritis  1  1/53 (1.89%)  1 1/51 (1.96%)  1 0/51 (0.00%)  0 1/50 (2.00%)  1 3/138 (2.17%)  3
Abdominal discomfort  1  2/53 (3.77%)  2 1/51 (1.96%)  1 1/51 (1.96%)  1 1/50 (2.00%)  1 0/138 (0.00%)  0
Constipation  1  2/53 (3.77%)  3 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  2
Proctitis  1  1/53 (1.89%)  1 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 3/138 (2.17%)  4
Faeces soft  1  1/53 (1.89%)  1 0/51 (0.00%)  0 1/51 (1.96%)  1 2/50 (4.00%)  2 0/138 (0.00%)  0
Haematochezia  1  1/53 (1.89%)  1 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Anal fissure  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  2
Anal fistula  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  2
Anogenital dysplasia  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Aphthous ulcer  1  1/53 (1.89%)  4 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Epigastric discomfort  1  1/53 (1.89%)  1 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Flatulence  1  1/53 (1.89%)  1 1/51 (1.96%)  3 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Inguinal hernia  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Rectal haemorrhage  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 1/50 (2.00%)  1 0/138 (0.00%)  0
Abdominal distension  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Abdominal pain lower  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Anal pruritus  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Anal skin tags  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Anal sphincter hypertonia  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Anal ulcer  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Anorectal disorder  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Anorectal ulcer  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Change of bowel habit  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Chronic gastritis  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Dental caries  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Enteritis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  3
Enterocolitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Food poisoning  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  2 0/138 (0.00%)  0
Gastrointestinal disorder  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Hiatus hernia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Hypoaesthesia oral  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Intestinal polyp  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Leukoplakia oral  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Odynophagia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Pancreatic atrophy  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Perianal erythema  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Rectal polyp  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Stomatitis  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Tongue discolouration  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Tongue disorder  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Umbilical hernia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
General disorders           
Pyrexia  1  5/53 (9.43%)  5 4/51 (7.84%)  4 1/51 (1.96%)  1 4/50 (8.00%)  5 6/138 (4.35%)  9
Fatigue  1  2/53 (3.77%)  2 4/51 (7.84%)  7 2/51 (3.92%)  2 6/50 (12.00%)  6 3/138 (2.17%)  4
Asthenia  1  4/53 (7.55%)  4 2/51 (3.92%)  3 1/51 (1.96%)  1 0/50 (0.00%)  0 3/138 (2.17%)  3
Influenza like illness  1  1/53 (1.89%)  1 0/51 (0.00%)  0 2/51 (3.92%)  2 1/50 (2.00%)  1 3/138 (2.17%)  3
Chest pain  1  1/53 (1.89%)  1 1/51 (1.96%)  1 0/51 (0.00%)  0 2/50 (4.00%)  2 2/138 (1.45%)  2
Malaise  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 1/50 (2.00%)  1 2/138 (1.45%)  2
Oedema peripheral  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  2
Pain  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 1/138 (0.72%)  1
Adverse drug reaction  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Chest discomfort  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Drug intolerance  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Feeling drunk  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Feeling hot  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
General physical health deterioration  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Injection site pain  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Nodule  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Oedema  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Hepatobiliary disorders           
Hypertransaminasaemia  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 1/50 (2.00%)  1 1/138 (0.72%)  1
Hepatic steatosis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  2
Cholestasis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Immune system disorders           
Seasonal allergy  1  1/53 (1.89%)  1 2/51 (3.92%)  2 1/51 (1.96%)  1 0/50 (0.00%)  0 2/138 (1.45%)  2
Allergy to arthropod sting  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Drug hypersensitivity  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  2 0/138 (0.00%)  0
Food allergy  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Hypersensitivity  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Multiple allergies  1  1/53 (1.89%)  2 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Infections and infestations           
Viral upper respiratory tract infection  1  7/53 (13.21%)  10 7/51 (13.73%)  10 6/51 (11.76%)  10 5/50 (10.00%)  7 20/138 (14.49%)  27
Bronchitis  1  5/53 (9.43%)  7 2/51 (3.92%)  3 2/51 (3.92%)  3 5/50 (10.00%)  6 10/138 (7.25%)  14
Influenza  1  5/53 (9.43%)  5 5/51 (9.80%)  6 4/51 (7.84%)  4 3/50 (6.00%)  3 6/138 (4.35%)  9
Syphilis  1  1/53 (1.89%)  1 3/51 (5.88%)  3 1/51 (1.96%)  1 4/50 (8.00%)  4 12/138 (8.70%)  15
Respiratory tract infection  1  4/53 (7.55%)  6 1/51 (1.96%)  2 2/51 (3.92%)  3 3/50 (6.00%)  4 9/138 (6.52%)  13
Upper respiratory tract infection  1  2/53 (3.77%)  2 3/51 (5.88%)  4 6/51 (11.76%)  8 1/50 (2.00%)  1 7/138 (5.07%)  10
Sinusitis  1  2/53 (3.77%)  3 2/51 (3.92%)  3 3/51 (5.88%)  4 4/50 (8.00%)  6 6/138 (4.35%)  6
Pharyngitis  1  3/53 (5.66%)  3 3/51 (5.88%)  3 1/51 (1.96%)  1 2/50 (4.00%)  2 3/138 (2.17%)  3
Gastroenteritis  1  0/53 (0.00%)  0 1/51 (1.96%)  1 2/51 (3.92%)  2 1/50 (2.00%)  1 5/138 (3.62%)  5
Rhinitis  1  1/53 (1.89%)  1 0/51 (0.00%)  0 2/51 (3.92%)  2 0/50 (0.00%)  0 5/138 (3.62%)  7
Tonsillitis  1  3/53 (5.66%)  10 1/51 (1.96%)  1 0/51 (0.00%)  0 1/50 (2.00%)  2 3/138 (2.17%)  5
Oral herpes  1  4/53 (7.55%)  4 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  2
Respiratory tract infection viral  1  3/53 (5.66%)  4 1/51 (1.96%)  4 0/51 (0.00%)  0 1/50 (2.00%)  1 2/138 (1.45%)  2
Folliculitis  1  0/53 (0.00%)  0 1/51 (1.96%)  1 1/51 (1.96%)  1 0/50 (0.00%)  0 4/138 (2.90%)  4
Herpes simplex  1  1/53 (1.89%)  1 0/51 (0.00%)  0 1/51 (1.96%)  1 1/50 (2.00%)  1 3/138 (2.17%)  3
Tooth abscess  1  2/53 (3.77%)  2 1/51 (1.96%)  1 1/51 (1.96%)  1 0/50 (0.00%)  0 2/138 (1.45%)  2
Tooth infection  1  0/53 (0.00%)  0 2/51 (3.92%)  3 1/51 (1.96%)  1 0/50 (0.00%)  0 3/138 (2.17%)  3
Urinary tract infection  1  1/53 (1.89%)  1 0/51 (0.00%)  0 2/51 (3.92%)  2 0/50 (0.00%)  0 3/138 (2.17%)  3
Viral infection  1  1/53 (1.89%)  1 3/51 (5.88%)  3 0/51 (0.00%)  0 1/50 (2.00%)  1 1/138 (0.72%)  3
Cellulitis  1  0/53 (0.00%)  0 1/51 (1.96%)  1 1/51 (1.96%)  1 2/50 (4.00%)  2 1/138 (0.72%)  1
Fungal skin infection  1  1/53 (1.89%)  1 1/51 (1.96%)  1 1/51 (1.96%)  2 1/50 (2.00%)  1 1/138 (0.72%)  1
Herpes zoster  1  1/53 (1.89%)  1 1/51 (1.96%)  1 1/51 (1.96%)  1 0/50 (0.00%)  0 2/138 (1.45%)  2
Acarodermatitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 3/138 (2.17%)  5
Chlamydial infection  1  1/53 (1.89%)  1 1/51 (1.96%)  1 0/51 (0.00%)  0 1/50 (2.00%)  1 1/138 (0.72%)  1
Conjunctivitis  1  0/53 (0.00%)  0 2/51 (3.92%)  2 1/51 (1.96%)  1 0/50 (0.00%)  0 1/138 (0.72%)  1
Ear infection  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 2/138 (1.45%)  2
Furuncle  1  1/53 (1.89%)  1 0/51 (0.00%)  0 2/51 (3.92%)  3 0/50 (0.00%)  0 1/138 (0.72%)  1
Gonorrhoea  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 1/50 (2.00%)  1 2/138 (1.45%)  2
Onychomycosis  1  0/53 (0.00%)  0 1/51 (1.96%)  1 0/51 (0.00%)  0 1/50 (2.00%)  1 2/138 (1.45%)  2
Otitis media  1  3/53 (5.66%)  4 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Urethritis  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 2/138 (1.45%)  2
Gastroenteritis viral  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 1/50 (2.00%)  1 1/138 (0.72%)  1
Herpes virus infection  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 1/138 (0.72%)  1
Nasopharyngitis  1  1/53 (1.89%)  1 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  2
Pharyngitis streptococcal  1  0/53 (0.00%)  0 1/51 (1.96%)  1 1/51 (1.96%)  1 0/50 (0.00%)  0 1/138 (0.72%)  1
Tinea pedis  1  1/53 (1.89%)  1 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 1/138 (0.72%)  1
Amoebic dysentery  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 1/50 (2.00%)  1 0/138 (0.00%)  0
Angular cheilitis  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 0/138 (0.00%)  0
Bacteriuria  1  1/53 (1.89%)  1 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Body tinea  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Cystitis  1  1/53 (1.89%)  1 1/51 (1.96%)  1 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Dermatophytosis  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Diverticulitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  3
Fungal infection  1  1/53 (1.89%)  1 1/51 (1.96%)  2 0/51 (0.00%)  0 0/50 (0.00%)  0 0/138 (0.00%)  0
Genital herpes  1  0/53 (0.00%)  0 0/51 (0.00%)  0 2/51 (3.92%)  2 0/50 (0.00%)  0 0/138 (0.00%)  0
Giardiasis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 1/138 (0.72%)  1
Hepatitis C  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 1/138 (0.72%)  1
Laryngitis  1  0/53 (0.00%)  0 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 1/138 (0.72%)  1
Molluscum contagiosum  1  0/53 (0.00%)  0 0/51 (0.00%)  0 2/51 (3.92%)  2 0/50 (0.00%)  0 0/138 (0.00%)  0
Otitis externa  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  2
Papilloma viral infection  1  1/53 (1.89%)  1 0/51 (0.00%)  0 1/51 (1.96%)  1 0/50 (0.00%)  0 0/138 (0.00%)  0
Shigella infection  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  2
Staphylococcal infection  1  0/53 (0.00%)  0 1/51 (1.96%)  2 0/51 (0.00%)  0 1/50 (2.00%)  3 0/138 (0.00%)  0
Subcutaneous abscess  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 2/138 (1.45%)  2
Superinfection bacterial  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  1 1/138 (0.72%)  1
Vulvovaginal mycotic infection  1  1/53 (1.89%)  1 0/51 (0.00%)  0 0/51 (0.00%)  0 1/50 (2.00%)  2 0/138 (0.00%)  0
Acute hepatitis C  1  0/53 (0.00%)  0 0/51 (0.00%)  0 0/51 (0.00%)  0 0/50 (0.00%)  0 1/138 (0.72%)  1
Acute sinusitis  1