Trial Outcomes & Findings for An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir Plus Lamivudine With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Subjects (Gemini 1) (NCT NCT02831673)

NCT ID: NCT02831673

Last Updated: 2023-08-24

Results Overview

Percentage of participants with HIV-1 RNA\<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights. Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all randomized participants who received at least one dose of study treatment. Percentage values are rounded to the nearest whole digit.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 719 participants
• Primary outcome timeframe: Week 48
• Results posted on: 2023-08-24

Participant Flow

This study is a randomized, double-blind, parallel-group, non-inferiority study. The study consisted of double blind, open label, and continuation phase.

Total of 719 participants were enrolled and randomized. Five participants were randomized but not treated. A total of 714 participants received at least one dose of study treatment, following randomization creating the intent to treat exposed (ITT-E) population.

Participant milestones

Measure	DTG + 3TC-Double Blind Phase Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.	DTG + 3TC - Open-label Phase Participants received a two-drug regimen of DTG + 3TC administered orally, once daily from Week 96 to Week 148 in the open-label phase.	DTG + TDF/FTC - Open-label Phase Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily from Week 96 to Week 148 in the open-label phase.	DTG + 3TC - Continuation Phase Participants received a DTG + 3TC administered orally, once daily from Week 148 to Week 280 in a continuation phase.
Double-blind (Day 1 to Week 96) STARTED	359	360	0	0	0
Double-blind (Day 1 to Week 96) Intent to Treat Exposed	356	358	0	0	0
Double-blind (Day 1 to Week 96) COMPLETED	301	320	0	0	0
Double-blind (Day 1 to Week 96) NOT COMPLETED	58	40	0	0	0
Open-label Phase (Week 96 to Week 148) STARTED	0	0	301	319	0
Open-label Phase (Week 96 to Week 148) COMPLETED	0	0	281	294	0
Open-label Phase (Week 96 to Week 148) NOT COMPLETED	0	0	20	25	0
Continuation Phase(Week 148 to Week 280) STARTED	0	0	0	0	233
Continuation Phase(Week 148 to Week 280) COMPLETED	0	0	0	0	212
Continuation Phase(Week 148 to Week 280) NOT COMPLETED	0	0	0	0	21

Reasons for withdrawal

Measure	DTG + 3TC-Double Blind Phase Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.	DTG + 3TC - Open-label Phase Participants received a two-drug regimen of DTG + 3TC administered orally, once daily from Week 96 to Week 148 in the open-label phase.	DTG + TDF/FTC - Open-label Phase Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily from Week 96 to Week 148 in the open-label phase.	DTG + 3TC - Continuation Phase Participants received a DTG + 3TC administered orally, once daily from Week 148 to Week 280 in a continuation phase.
Double-blind (Day 1 to Week 96) Adverse Event	10	7	0	0	0
Double-blind (Day 1 to Week 96) Lack of Efficacy	4	2	0	0	0
Double-blind (Day 1 to Week 96) Protocol Deviation	6	6	0	0	0
Double-blind (Day 1 to Week 96) Protocol Withdrawal Criterion Met	2	6	0	0	0
Double-blind (Day 1 to Week 96) Lost to Follow-up	13	7	0	0	0
Double-blind (Day 1 to Week 96) Physician Decision	9	4	0	0	0
Double-blind (Day 1 to Week 96) Withdrawal by Subject	11	6	0	0	0
Double-blind (Day 1 to Week 96) Randomized but not treated	3	2	0	0	0
Open-label Phase (Week 96 to Week 148) Adverse Event	0	0	3	6	0
Open-label Phase (Week 96 to Week 148) Lack of Efficacy	0	0	1	2	0
Open-label Phase (Week 96 to Week 148) Protocol Deviation	0	0	0	1	0
Open-label Phase (Week 96 to Week 148) Protocol-Specified Withdrawal Criterion Met	0	0	2	1	0
Open-label Phase (Week 96 to Week 148) Lost to Follow-up	0	0	7	6	0
Open-label Phase (Week 96 to Week 148) Physician Decision	0	0	1	4	0
Open-label Phase (Week 96 to Week 148) Withdrawal by Subject	0	0	6	5	0
Continuation Phase(Week 148 to Week 280) Adverse Event	0	0	0	0	1
Continuation Phase(Week 148 to Week 280) Protocol Deviation	0	0	0	0	1
Continuation Phase(Week 148 to Week 280) Lost to Follow-up	0	0	0	0	10
Continuation Phase(Week 148 to Week 280) Physician Decision	0	0	0	0	2
Continuation Phase(Week 148 to Week 280) Withdrawal by Subject	0	0	0	0	7

Baseline Characteristics

An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir Plus Lamivudine With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Subjects (Gemini 1)

Baseline characteristics by cohort

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.	Total n=714 Participants Total of all reporting groups
Age, Continuous	34.0 Years STANDARD_DEVIATION 9.88 • n=93 Participants	35.0 Years STANDARD_DEVIATION 10.72 • n=4 Participants	34.5 Years STANDARD_DEVIATION 10.31 • n=27 Participants
Sex: Female, Male Female	59 Participants n=93 Participants	52 Participants n=4 Participants	111 Participants n=27 Participants
Sex: Female, Male Male	297 Participants n=93 Participants	306 Participants n=4 Participants	603 Participants n=27 Participants
Race/Ethnicity, Customized Race · American (Am) Indian or Alaska (Al.) native	31 Participants n=93 Participants	28 Participants n=4 Participants	59 Participants n=27 Participants
Race/Ethnicity, Customized Race · Asian-Central/South Asian heritage (H.)	0 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants
Race/Ethnicity, Customized Race · Asian - East Asian H.	33 Participants n=93 Participants	36 Participants n=4 Participants	69 Participants n=27 Participants
Race/Ethnicity, Customized Race · Asian - South East Asian H.	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Race/Ethnicity, Customized Race · Black or African Am	39 Participants n=93 Participants	36 Participants n=4 Participants	75 Participants n=27 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or other Pacific Islander	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized Race · White (Wt)-Arabic/North African H.	5 Participants n=93 Participants	5 Participants n=4 Participants	10 Participants n=27 Participants
Race/Ethnicity, Customized Race · White - White/Caucasian/European H.	239 Participants n=93 Participants	242 Participants n=4 Participants	481 Participants n=27 Participants
Race/Ethnicity, Customized Race · Multiple	3 Participants n=93 Participants	5 Participants n=4 Participants	8 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 48

Population: ITT-E Population

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights. Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all randomized participants who received at least one dose of study treatment. Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL (c/mL) at Week 48	90 Percentage of participants Interval 86.8 to 93.0	93 Percentage of participants Interval 90.0 to 95.4

SECONDARY outcome

Timeframe: Week 24

Population: ITT-E Population

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel weights. Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24	92 Percentage of participants Interval 89.7 to 95.2	93 Percentage of participants Interval 90.4 to 95.7

SECONDARY outcome

Timeframe: Week 96

Population: ITT-E Population

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel weights. Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 96	84 Percentage of participants Interval 80.5 to 88.1	89 Percentage of participants Interval 86.2 to 92.6

SECONDARY outcome

Timeframe: Week 144

Population: ITT-E Population

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. This endpoint was analyzed using a stratified analysis with CMH weights. Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 144	79 Percentage of participants Interval 74.7 to 83.2	83 Percentage of participants Interval 78.8 to 86.6

SECONDARY outcome

Timeframe: Up to Week 144

Population: ITT-E Population

Time of viral suppression is defined as the first viral load value <50 c/mL. Nonparametric Kaplan-Meier method was performed. Participants who withdrew for any reason without being suppressed were censored at date of withdrawal. Participants who have not been withdrawn and have not had viral suppression at time of the analysis were censored at last viral load date. Confidence Interval (CI) was estimated using the Brookmeyer-Crowley method.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Time to Viral Suppression (HIV-1 RNA <50 c/mL) up to Week 144	29.0 Days Interval 29.0 to 53.0	29.0 Days Interval 29.0 to 56.0

SECONDARY outcome

Timeframe: Weeks 24 and 48

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
CD4+ Cell Counts at Weeks 24 and 48 Week 24, n=340,341	655.3 Cells per cubic millimeter (cells/mm^3) Standard Deviation 288.32	632.8 Cells per cubic millimeter (cells/mm^3) Standard Deviation 262.61
CD4+ Cell Counts at Weeks 24 and 48 Week 48, n=324,334	687.7 Cells per cubic millimeter (cells/mm^3) Standard Deviation 275.47	675.3 Cells per cubic millimeter (cells/mm^3) Standard Deviation 274.46

SECONDARY outcome

Timeframe: Week 96

Population: ITT-E Population. Only those participants available at the specified time points were analyzed

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+ cells. Analysis was performed by flow cytometry.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=301 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=320 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
CD4+ Cell Counts at Week 96	732.8 Cells per cubic millimeter (cells/mm^3) Standard Deviation 298.05	711.5 Cells per cubic millimeter (cells/mm^3) Standard Deviation 284.15

SECONDARY outcome

Timeframe: Week 144

Population: ITT-E Population. Only those participants available at the specified time points were analyzed

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+ cells. Analysis was performed by flow cytometry.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=270 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=287 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
CD4+ Cell Counts at Week 144	767.8 Cells per cubic millimeter (cells/mm^3) Standard Deviation 274.00	758.2 Cells per cubic millimeter (cells/mm^3) Standard Deviation 285.35

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 24, 48

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is defined as the the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Changes From Baseline in CD4+ Cell Counts at Week 24 and 48 Week 24, n=340,341	192.2 Cells per cubic millimeter Standard Error 9.67	175.1 Cells per cubic millimeter Standard Error 9.41
Changes From Baseline in CD4+ Cell Counts at Week 24 and 48 Week 48, n=324,334	222.2 Cells per cubic millimeter Standard Error 9.87	217.7 Cells per cubic millimeter Standard Error 10.64

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 96

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+ cells. Analysis was performed by flow cytometry. Baseline value is defined as the the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=301 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=320 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Changes From Baseline in CD4+ Cell Counts at Week 96	264.7 Cells per cubic millimeter Standard Error 11.32	253.8 Cells per cubic millimeter Standard Error 11.40

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 144

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+ cells. Analysis was performed by flow cytometry. Baseline value is defined as the the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=270 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=287 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Changes From Baseline in CD4+ Cell Counts at Week 144	301.8 Cells per cubic millimeter Standard Error 11.51	303.2 Cells per cubic millimeter Standard Error 12.13

SECONDARY outcome

Timeframe: Up to Week 144

Population: ITT-E Population

HIV-associated conditions were recorded during the study and was assessed according to the 2014 Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection in Adults. Disease progressions summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrollment to Stage 3 event; CDC Category Stage 2 at enrolment to Stage 3 event; CDC Category Stage 3 at enrollment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrolment to Death.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants With HIV-1 Disease Progression up to Week 144 No HIV-1 disease progression	352 Participants	356 Participants
Number of Participants With HIV-1 Disease Progression up to Week 144 From CDC Stage 1 to CDC Stage 3 Event	0 Participants	0 Participants
Number of Participants With HIV-1 Disease Progression up to Week 144 From CDC Stage 2 to CDC Stage 3 Event	2 Participants	2 Participants
Number of Participants With HIV-1 Disease Progression up to Week 144 From CDC Stage 3 to New CDC Stage 3 Event	1 Participants	0 Participants
Number of Participants With HIV-1 Disease Progression up to Week 144 From CDC Stage 1, 2 or 3 to Death	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 144

Population: Viral Genotypic Population. Only those participants available at the specified time points were analyzed.

Number of participants, who met confirmed virologic withdrawal (CVW) criteria, with treatment emergent genotypic resistance to Integrase strand transfer inhibitor (INSTI) and/or Nucleoside reverse transcriptase inhibitor (NRTI) was summarized. The Viral Genotypic Population comprised of all participants in the ITT-E population who have available on-treatment genotypic resistance data.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=8 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=8 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants With Treatment-emergent Genotypic Resistance up to Week 144 INSTI Mutations	0 Participants	0 Participants
Number of Participants With Treatment-emergent Genotypic Resistance up to Week 144 Major mutations of NRTI	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 144

Population: Viral Phenotypic Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Number of participants, who meet CVW criteria, with treatment emergent phenotypic resistance to INSTI and/or NRTI were summarized. Assessment of antiviral activity of anti-retroviral therapy (ART) using phenotypic test results was interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. The Viral Phenotypic Population comprised of all participants in the ITT-E population who have available on-treatment phenotypic resistance data.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=5 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=6 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, TDF, Resistant, n=5,5	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, 3TC, Resistant, n=5,5	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, ABC, Sensitive, n=5,5	5 Participants	5 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, ABC, Resistant, n=5,5	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, AZT, Sensitive, n=5,5	5 Participants	5 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, AZT, Resistant, n=5,5	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, D4T, Sensitive, n=5,5	5 Participants	5 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, D4T, Resistant, n=5,5	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, DDI, Sensitive, n=5,5	5 Participants	5 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, DDI, Resistant, n=5,5	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, FTC, Sensitive, n=5,5	5 Participants	5 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, FTC, Resistant, n=5,5	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, TDF, Sensitive, n=5,5	5 Participants	5 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 INSTI, DTG, Sensitive, n=,5,4	5 Participants	4 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 INSTI, DTG, Resistant, n=5,4	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 INSTI, EGV, Sensitive, n=5,4	5 Participants	4 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 INSTI, EGV, Resistant, n=5,4	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 INSTI, RAL, Sensitive, n=5,4	5 Participants	4 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 INSTI, RAL, Resistant, n=5,4	0 Participants	0 Participants
Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 NRTI, 3TC, Sensitive, n=5,5	5 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to Week 148

Population: Safety Population

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or protocol defined event associated with liver injury and impaired liver function were categorized as SAE. Safety Population was used which comprised of all participants who received at least one dose of study treatment.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants With Any AE and SAE up to Week 148 Any AE	307 Participants	316 Participants
Number of Participants With Any AE and SAE up to Week 148 Any SAE	37 Participants	38 Participants

SECONDARY outcome

Timeframe: Up to Week 144

Population: Safety Population

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants With AEs by Maximum Severity Grades up to Week 144 Grade 1 AEs	33 Participants	35 Participants
Number of Participants With AEs by Maximum Severity Grades up to Week 144 Grade 2 AEs	229 Participants	242 Participants
Number of Participants With AEs by Maximum Severity Grades up to Week 144 Grade 3 AEs	37 Participants	34 Participants
Number of Participants With AEs by Maximum Severity Grades up to Week 144 Grade 4 AEs	7 Participants	5 Participants
Number of Participants With AEs by Maximum Severity Grades up to Week 144 Grade 5 AEs	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 144

Population: Safety Population

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5. (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with drug related AEs and drug related AEs by by maximum grade have been presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 144 Any drug related AE	77 Participants	101 Participants
Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 144 Drug related AEs with maximum toxicity Grade 1	51 Participants	70 Participants
Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 144 Drug related AEs with maximum toxicity Grade 2	19 Participants	28 Participants
Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 144 Drug related AEs with maximum toxicity Grade 3	7 Participants	3 Participants
Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 144 Drug related AEs with maximum toxicity Grade 4	0 Participants	0 Participants
Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 144 Drug related AEs with maximum toxicity Grade 5	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 144

Population: Safety Population

Blood samples were collected up to Week 144 for assessment of hemoglobin, leukocytes, neutrophils and platelets. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the listed hematology parameters have been presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Hemoglobin, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Hemoglobin, Grade 1	8 Participants	6 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Hemoglobin, Grade 2	1 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Hemoglobin, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Hemoglobin, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Leukocytes, Grades 1 to 4	16 Participants	3 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Leukocytes, Grades 2 to 4	4 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Leukocytes, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Leukocytes, Grade 1	12 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Leukocytes, Grade 2	4 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Leukocytes, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Leukocytes, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Neutrophils, Grades 1 to 4	25 Participants	18 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Neutrophils, Grades 2 to 4	19 Participants	11 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Neutrophils, Grades 3 to 4	7 Participants	6 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Neutrophils, Grade 1	6 Participants	7 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Neutrophils, Grade 2	12 Participants	5 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Neutrophils, Grade 3	5 Participants	5 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Neutrophils, Grade 4	2 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Platelets, Grades 1 to 4	14 Participants	11 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Platelets, Grades 2 to 4	8 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Platelets, Grades 3 to 4	1 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Platelets, Grade 1	6 Participants	7 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Platelets, Grade 2	7 Participants	3 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Platelets, Grade 3	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Platelets, Grade 4	1 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Hemoglobin, Grades 1 to 4	9 Participants	7 Participants
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 Hemoglobin, Grades 2 to 4	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Week 144

Population: Safety Population

Blood samples were collected up to Week 144 for assessment of Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate aminotransferase (AST), Bilirubin, Carbon dioxide (CO2), Cholesterol, Creatine kinase (CK), Creatinine, Direct Bilirubin, Glomerular filtration rate (GFR) from creatinine adjusted for body surface area (BSA), Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypernatremia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hyponatremia, Low density lipid (LDL) Cholesterol, Lactate Dehydrogenase, Lipase, Phosphate, and Triglycerides. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CO2, Grade 1	118 Participants	107 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALT, Grades 1 to 4	55 Participants	81 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALT, Grades 2 to 4	23 Participants	25 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALT, Grades 3 to 4	14 Participants	9 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALT, Grade 1	32 Participants	56 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALT, Grade 2	9 Participants	16 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALT, Grade 3	7 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALT, Grade 4	7 Participants	5 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Albumin, Grades 1 to 4	1 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Albumin, Grades 2 to 4	1 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Albumin, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Albumin, Grade 1	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Albumin, Grade 2	1 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Albumin, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Albumin, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALP, Grades 1 to 4	8 Participants	10 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALP, Grades 2 to 4	3 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALP, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALP, Grade 1	5 Participants	9 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALP, Grade 2	3 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALP, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 ALP, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 AST, Grades 1 to 4	52 Participants	79 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 AST, Grades 2 to 4	27 Participants	31 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 AST, Grades 3 to 4	8 Participants	13 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 AST, Grade 1	25 Participants	48 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 AST, Grade 2	19 Participants	18 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 AST, Grade 3	6 Participants	9 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 AST, Grade 4	2 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Bilirubin, Grades 1 to 4	42 Participants	51 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Bilirubin, Grades 2 to 4	14 Participants	17 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Bilirubin, Grades 3 to 4	4 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Bilirubin, Grade 1	28 Participants	34 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Bilirubin, Grade 2	10 Participants	13 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Bilirubin, Grade 3	2 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Bilirubin, Grade 4	2 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CO2, Grades 1 to 4	126 Participants	116 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CO2, Grades 2 to 4	8 Participants	9 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CO2, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CO2, Grade 2	8 Participants	9 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CO2, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CO2, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Cholesterol, Grades 1 to 4	77 Participants	40 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Cholesterol, Grades 2 to 4	24 Participants	13 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Cholesterol, Grades 3 to 4	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Cholesterol, Grade 1	53 Participants	27 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Cholesterol, Grade 2	24 Participants	12 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Cholesterol, Grade 3	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Cholesterol, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CK, Grades 1 to 4	76 Participants	75 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CK, Grades 2 to 4	43 Participants	52 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CK, Grades 3 to 4	26 Participants	36 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CK, Grade 1	33 Participants	23 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CK, Grade 2	17 Participants	16 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CK, Grade 3	15 Participants	21 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 CK, Grade 4	11 Participants	15 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Creatinine, Grades 1 to 4	21 Participants	31 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Creatinine, Grades 2 to 4	1 Participants	3 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Creatinine, Grades 3 to 4	0 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Creatinine, Grade 1	20 Participants	28 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Creatinine, Grade 2	1 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Creatinine, Grade 3	0 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Creatinine, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Direct Bilirubin, Grades 1 to 4	14 Participants	13 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Direct Bilirubin, Grades 2 to 4	14 Participants	13 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Direct Bilirubin, Grades 3 to 4	14 Participants	13 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Direct Bilirubin, Grade 1	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Direct Bilirubin, Grade 2	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Direct Bilirubin, Grade 3	14 Participants	13 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Direct Bilirubin, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 GFR from creatinine adjusted for BSA Grades 1 to 4	185 Participants	226 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 GFR from creatinine adjusted for BSA Grades 2 to 4	185 Participants	226 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 GFR from creatinine adjusted for BSA Grades 3 to 4	13 Participants	27 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 GFR from creatinine adjusted for BSA, Grade 1	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 GFR from creatinine adjusted for BSA, Grade 2	172 Participants	199 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 GFR from creatinine adjusted for BSA Grades 3	13 Participants	25 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 GFR from creatinine adjusted for BSA, Grade 4	0 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypercalcaemia, Grades 1 to 4	7 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypercalcaemia, Grades 2 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypercalcaemia, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypercalcaemia, Grade 1	7 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypercalcaemia, Grade 2	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypercalcaemia, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypercalcaemia, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperglycemia, Grades 1 to 4	91 Participants	81 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperglycemia, Grades 2 to 4	38 Participants	25 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperglycemia, Grades 3 to 4	3 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperglycemia, Grade 1	53 Participants	56 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperglycemia, Grade 2	35 Participants	23 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperglycemia, Grade 3	3 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperglycemia, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperkalemia, Grades 1 to 4	1 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperkalemia, Grades 2 to 4	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperkalemia, Grades 3 to 4	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperkalemia, Grade 1	1 Participants	3 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperkalemia, Grade 2	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperkalemia, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyperkalemia, Grade 4	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypernatremia, Grades 1 to 4	6 Participants	3 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypernatremia, Grades 2 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypernatremia, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypernatremia, Grade 1	6 Participants	3 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypernatremia, Grade 2	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypernatremia, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypernatremia, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypocalcaemia, Grades 1 to 4	14 Participants	13 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypocalcaemia, Grades 2 to 4	4 Participants	3 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypocalcaemia, Grades 3 to 4	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypocalcaemia, Grade 1	10 Participants	10 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypocalcaemia, Grade 2	4 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypocalcaemia, Grade 3	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypocalcaemia, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypoglycemia, Grades 1 to 4	22 Participants	17 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypoglycemia, Grades 2 to 4	8 Participants	3 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypoglycemia, Grades 3 to 4	2 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypoglycemia, Grade 1	14 Participants	14 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypoglycemia, Grade 2	6 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypoglycemia, Grade 3	1 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypoglycemia, Grade 4	1 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypokalemia, Grades 1 to 4	6 Participants	7 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypokalemia, Grades 2 to 4	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypokalemia, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypokalemia, Grade 1	6 Participants	6 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypokalemia, Grade 2	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypokalemia, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hypokalemia, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyponatremia, Grades 1 to 4	25 Participants	28 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyponatremia, Grades 2 to 4	2 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyponatremia, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyponatremia, Grade 1	23 Participants	28 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyponatremia, Grade 2	2 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyponatremia, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Hyponatremia, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 LDL Cholesterol, Grades 1 to 4	57 Participants	35 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 LDL Cholesterol, Grades 2 to 4	17 Participants	14 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 LDL Cholesterol, Grades 3 to 4	5 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 LDL Cholesterol, Grade 1	40 Participants	21 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 LDL Cholesterol, Grade 2	12 Participants	10 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 LDL Cholesterol, Grade 3	5 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 LDL Cholesterol, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lactate Dehydrogenase, Grades 1 to 4	3 Participants	5 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lactate Dehydrogenase, Grades 2 to 4	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lactate Dehydrogenase, Grades 3 to 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lactate Dehydrogenase, Grade 1	3 Participants	4 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lactate Dehydrogenase, Grade 2	0 Participants	1 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lactate Dehydrogenase, Grade 3	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lactate Dehydrogenase, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lipase, Grades 1 to 4	65 Participants	80 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lipase, Grades 2 to 4	35 Participants	49 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lipase, Grades 3 to 4	10 Participants	18 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lipase, Grade 1	30 Participants	31 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lipase, Grade 2	25 Participants	31 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lipase, Grade 3	8 Participants	10 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Lipase, Grade 4	2 Participants	8 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Phosphate, Grades 1 to 4	70 Participants	68 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Phosphate, Grades 2 to 4	35 Participants	47 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Phosphate, Grades 3 to 4	2 Participants	6 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Phosphate, Grade 1	35 Participants	21 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Phosphate, Grade 2	33 Participants	41 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Phosphate, Grade 3	2 Participants	6 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Phosphate, Grade 4	0 Participants	0 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Triglycerides, Grades 1 to 4	80 Participants	62 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Triglycerides, Grades 2 to 4	12 Participants	14 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Triglycerides, Grades 3 to 4	7 Participants	3 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Triglycerides, Grade 1	68 Participants	48 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Triglycerides, Grade 2	5 Participants	11 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Triglycerides, Grade 3	6 Participants	2 Participants
Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 Triglycerides, Grade 4	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Week 24, Week 48 and Week 96

Population: Safety Population

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. . Number of participants who discontinued treatment due to AEs have been reported.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48, 96 Up to Week 24	6 Participants	4 Participants
Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48, 96 Up to Week 48	7 Participants	8 Participants
Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48, 96 Up to Week 96	14 Participants	11 Participants

SECONDARY outcome

Timeframe: Up to Week 144

Population: Safety Population

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants who discontinued treatment due to AEs have been reported.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Number of Participants Who Discontinue Treatment Due to AEs Over Week 144	18 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Weeks 24, 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Serum Cystatin C and Serum Retinol Binding Protein (RBP). Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48 Serum Cystatin C, Week 24, n=338, 336	-0.05 Milligrams per Liter (mg/L) Standard Error 0.007	-0.03 Milligrams per Liter (mg/L) Standard Error 0.007
Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48 Serum Cystatin C, Week 48, n=324, 332	-0.07 Milligrams per Liter (mg/L) Standard Error 0.007	-0.04 Milligrams per Liter (mg/L) Standard Error 0.006
Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48 Serum RBP, Week 24, n=332, 334	1.6 Milligrams per Liter (mg/L) Standard Error 0.41	1.9 Milligrams per Liter (mg/L) Standard Error 0.51
Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48 Serum RBP, Week 48, n=322, 332	0.5 Milligrams per Liter (mg/L) Standard Error 0.47	0.6 Milligrams per Liter (mg/L) Standard Error 0.46

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of renal inflammation biomarkers which included Serum Cystatin C . Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=300 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=319 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 96	-0.11 Milligrams per Liter (mg/L) Standard Error 0.006	-0.09 Milligrams per Liter (mg/L) Standard Error 0.006

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of renal biomarkers which included Serum Cystatin C. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Adjusted mean and standard error is presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=283 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=298 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 144	-0.12 Milligrams per Liter (mg/L) Standard Error 0.006	-0.11 Milligrams per Liter (mg/L) Standard Error 0.007

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood and/or urine samples were collected to perform evaluation of renal biomarkers which included Serum RBP. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=288 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=310 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarker-Serum RBP at Week 96	1.535 Microgram per millimoles (ug/mmol) Standard Deviation 8.5872	7.704 Microgram per millimoles (ug/mmol) Standard Deviation 41.9650

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood and/or urine samples were collected to perform evaluation of renal biomarkers which included Serum RBP. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=276 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=292 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarker-Serum RBP at Week 144	1.760 Microgram per millimoles (ug/mmol) Standard Deviation 5.7909	8.855 Microgram per millimoles (ug/mmol) Standard Deviation 35.5147

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Weeks 24, 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Serum GFR from cystatin C adjusted using CKD-EPI (GFR-cystatin C adjusted)and Serum or Plasma GFR from creatinine adjusted using CKD-EPI. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24, 48 GFR-cystatin C adjusted, Week 24, n=338, 336	4.4 Milliliter/minute/1.73*meter^2 Standard Error 0.63	2.2 Milliliter/minute/1.73*meter^2 Standard Error 0.60
Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24, 48 GFR-cystatin C adjusted, Week 48, n=324, 332	7.0 Milliliter/minute/1.73*meter^2 Standard Error 0.60	4.1 Milliliter/minute/1.73*meter^2 Standard Error 0.59
Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24, 48 GFR-creatinine adjusted, Week 24, n=340, 341	-13.5 Milliliter/minute/1.73*meter^2 Standard Error 0.59	-16.7 Milliliter/minute/1.73*meter^2 Standard Error 0.56
Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24, 48 GFR-creatinine adjusted, Week 48, n=326,335	-12.1 Milliliter/minute/1.73*meter^2 Standard Error 0.56	-15.6 Milliliter/minute/1.73*meter^2 Standard Error 0.55

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of renal biomarkers which included Serum GFR from cystatin C adjusted using CKD-EPI and Serum or Plasma GFR from creatinine adjusted for BSA using CKD-EPI. Baseline value is the latest pre-dose Assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=300 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=319 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI Method at Week 96 GFR Cystatin C adjusted, Week 96	11.3 Milliliter/minute/1.73*meter^2 Standard Deviation 14.54	9.3 Milliliter/minute/1.73*meter^2 Standard Deviation 13.78
Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI Method at Week 96 GFR creatinine adjusted, Week 96	-15.3 Milliliter/minute/1.73*meter^2 Standard Deviation 11.50	-19.0 Milliliter/minute/1.73*meter^2 Standard Deviation 11.25

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of renal biomarkers which included Serum GFR from cystatin C adjusted using CKD-EPI and Serum or Plasma GFR from creatinine adjusted for BSA using CKD-EPI. Baseline value is the latest pre-dose Assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI Method at Week 144 GFR Cystatin C adjusted, Week 144, n=283,298	13.0 Milliliter/minute/1.73*meter^2 Standard Deviation 13.64	12.1 Milliliter/minute/1.73*meter^2 Standard Deviation 15.24
Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI Method at Week 144 GFR creatinine adjusted, Week 144, n=271, 289	-16.7 Milliliter/minute/1.73*meter^2 Standard Deviation 11.65	-19.3 Milliliter/minute/1.73*meter^2 Standard Deviation 11.07

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Weeks 24, 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood and/or urine were collected to perform evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48 Serum or Plasma Creatinine, Week 24, n=340, 343	11.88 Micromoles per Liter (umol/L) Standard Error 0.510	15.07 Micromoles per Liter (umol/L) Standard Error 0.520
Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48 Serum or Plasma Creatinine, Week 48, n=326, 335	10.39 Micromoles per Liter (umol/L) Standard Error 0.466	13.61 Micromoles per Liter (umol/L) Standard Error 0.480

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood and/or urine were collected to perform evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=300 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=319 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 96	12.75 Micromoles per Liter (umol/L) Standard Error 0.623	16.10 Micromoles per Liter (umol/L) Standard Error 0.539

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood and/or urine were collected to perform evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=271 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=289 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 144	12.89 Micromoles per Liter (umol/L) Standard Error 0.583	15.87 Micromoles per Liter (umol/L) Standard Error 0.560

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Weeks 24, 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Urine and Serum B2M, Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value is defined as the latest pre-dose assessment (Day 1). Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Statistical analysis of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Estimated ratio of geometric means (each visit over Baseline) and 95% confidence interval (CI) have been presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Serum B2M, Week 24, n=338, 335	0.798 Ratio Interval 0.779 to 0.817	0.872 Ratio Interval 0.856 to 0.89
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Serum B2M, Week 48, n=324, 332	0.806 Ratio Interval 0.79 to 0.823	0.892 Ratio Interval 0.876 to 0.908
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine B2M, Week 24, n=121, 95	0.887 Ratio Interval 0.756 to 1.039	1.351 Ratio Interval 1.06 to 1.722
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine B2M, Week 48, n=119, 103	0.900 Ratio Interval 0.792 to 1.022	1.338 Ratio Interval 1.148 to 1.56
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine Albumin/Creatinine, Week 24, n=254, 252	1.014 Ratio Interval 0.927 to 1.109	1.050 Ratio Interval 0.964 to 1.144
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine Albumin/Creatinine , Week 48, n=237, 244	0.934 Ratio Interval 0.857 to 1.017	1.048 Ratio Interval 0.968 to 1.134
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine B2M/Urine Creatinine, Week 24, n=121, 95	0.852 Ratio Interval 0.737 to 0.985	1.331 Ratio Interval 1.071 to 1.655
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine B2M/Urine Creatinine, Week 48, n=114, 100	0.888 Ratio Interval 0.777 to 1.015	1.278 Ratio Interval 1.119 to 1.458
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine Phosphate, Week 24, n=330, 332	1.115 Ratio Interval 1.025 to 1.212	1.012 Ratio Interval 0.934 to 1.095
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine Phosphate, Week 48, n=316, 330	1.061 Ratio Interval 0.983 to 1.145	1.075 Ratio Interval 0.996 to 1.159
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine Protein/Creatinine, Week 24, n=269, 265	0.850 Ratio Interval 0.806 to 0.895	1.016 Ratio Interval 0.96 to 1.075
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine Protein/Creatinine, Week 48, n=252, 269	0.879 Ratio Interval 0.838 to 0.922	1.061 Ratio Interval 1.009 to 1.115
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine RBP 4, Week 24, n=332, 330	0.934 Ratio Interval 0.842 to 1.036	1.073 Ratio Interval 0.951 to 1.209
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine RBP 4, Week 48, n=318, 328	1.115 Ratio Interval 1.009 to 1.233	1.490 Ratio Interval 1.332 to 1.667
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine RBP 4/Urine Creatinine, Week 24, n=329, 330	0.919 Ratio Interval 0.846 to 0.998	1.110 Ratio Interval 1.003 to 1.228
Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 Urine RBP 4/Urine Creatinine, Week 48, n=304, 318	1.147 Ratio Interval 1.06 to 1.241	1.500 Ratio Interval 1.367 to 1.646

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value is defined as the latest pre-dose assessment (Day 1). Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Statistical analysis of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Estimated ratio of geometric means (each visit over Baseline) and 95% confidence interval (CI) have been presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96 Urine Albumin/Creatinine, Week 96, n=222, 243	0.924 Ratio Interval 0.847 to 1.008	1.101 Ratio Interval 1.008 to 1.202
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96 Urine B2M/Urine Creatinine , Week 96, n=107, 104	0.794 Ratio Interval 0.72 to 0.877	1.441 Ratio Interval 1.193 to 1.74
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96 Urine Phosphate, Week 96, n=292, 316	1.113 Ratio Interval 1.021 to 1.214	1.066 Ratio Interval 0.984 to 1.155
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96 Urine Protein/Creatinine, Week 96, n=238, 258	0.868 Ratio Interval 0.818 to 0.92	1.053 Ratio Interval 1.004 to 1.105
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96 Urine RBP 4/Urine Creatinine, Week 96, n=289, 311	1.310 Ratio Interval 1.207 to 1.42	1.771 Ratio Interval 1.604 to 1.955

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Urine and Serum B2M, Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value is defined as the latest pre-dose assessment (Day 1). Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Statistical analysis of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Estimated ratio of geometric means (each visit over Baseline) and 95% confidence interval (CI) have been presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144 Urine Albumin/Creatinine , Week 144, n=207, 212	1.050 Ratio Interval 0.954 to 1.155	1.146 Ratio Interval 1.039 to 1.264
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144 Urine B2M/Urine Creatinine , Week 144, n=100, 102	0.751 Ratio Interval 0.679 to 0.83	1.518 Ratio Interval 1.281 to 1.799
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144 Urine Phosphate, Week 144, n=274, 294	1.040 Ratio Interval 0.954 to 1.133	0.955 Ratio Interval 0.879 to 1.037
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144 Urine Protein/Creatinine , Week 144, n=225,232	0.988 Ratio Interval 0.932 to 1.047	1.210 Ratio Interval 1.144 to 1.28
Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144 Urine RBP 4/Urine Creatinine, Week 144, n=276, 292	1.648 Ratio Interval 1.55 to 1.752	2.425 Ratio Interval 2.208 to 2.663

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Weeks 24, 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood samples were collected to perform evaluation of bone biomarkers which included bone-ALP, Serum Osteocalcin, PINP and CTX-1. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 Bone-ALP, Week 24, n=334, 332	0.91 Micrograms per Liter (ug/L) Standard Error 0.179	3.13 Micrograms per Liter (ug/L) Standard Error 0.199
Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 Bone-ALP, Week 48, n=321, 331	1.21 Micrograms per Liter (ug/L) Standard Error 0.193	3.79 Micrograms per Liter (ug/L) Standard Error 0.239
Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 Serum Osteocalcin, Week 24, n=335, 334	2.56 Micrograms per Liter (ug/L) Standard Error 0.341	6.74 Micrograms per Liter (ug/L) Standard Error 0.347
Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 Serum Osteocalcin, Week 48, n=322, 330	0.78 Micrograms per Liter (ug/L) Standard Error 0.311	6.01 Micrograms per Liter (ug/L) Standard Error 0.400
Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 PINP, Week 24, n=337, 336	4.5 Micrograms per Liter (ug/L) Standard Error 0.91	18.3 Micrograms per Liter (ug/L) Standard Error 1.06
Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 PINP, Week 48, n=321, 334	0.5 Micrograms per Liter (ug/L) Standard Error 0.83	13.1 Micrograms per Liter (ug/L) Standard Error 0.84
Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 CTX-1, Week 24, n=337, 334	0.1192 Micrograms per Liter (ug/L) Standard Error 0.01304	0.2820 Micrograms per Liter (ug/L) Standard Error 0.01472
Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 CTX-1, Week 48, n=323, 331	0.1338 Micrograms per Liter (ug/L) Standard Error 0.01258	0.3352 Micrograms per Liter (ug/L) Standard Error 0.01885

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood samples were collected to perform evaluation of bone biomarkers which included bone-ALP, Serum Osteocalcin, PINP and CTX-1. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 96 Bone-ALP, Week 96, n=296, 317	0.30 Micrograms per Liter (ug/L) Standard Error 0.191	2.37 Micrograms per Liter (ug/L) Standard Error 0.216
Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 96 Serum Osteocalcin, Week 96, n=297, 320	0.40 Micrograms per Liter (ug/L) Standard Error 0.345	4.57 Micrograms per Liter (ug/L) Standard Error 0.391
Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 96 PINP, Week 96, n=297, 319	15.0 Micrograms per Liter (ug/L) Standard Error 1.63	28.3 Micrograms per Liter (ug/L) Standard Error 1.50
Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 96 CTX-1, Week 96, n=297, 315	0.1351 Micrograms per Liter (ug/L) Standard Error 0.01580	0.2943 Micrograms per Liter (ug/L) Standard Error 0.01916

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood samples were collected to perform evaluation of bone biomarkers which included bone-ALP, Serum Osteocalcin, PINP and CTX-1. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 144 Bone-ALP, Week 144, n=281, 295	-0.25 Micrograms per Liter (ug/L) Standard Error 0.172	1.43 Micrograms per Liter (ug/L) Standard Error 0.217
Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 144 Serum Osteocalcin, Week 144, n=281, 299	0.29 Micrograms per Liter (ug/L) Standard Error 0.374	3.21 Micrograms per Liter (ug/L) Standard Error 0.403
Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 144 PINP, Week 144, n=281,299	4.6 Micrograms per Liter (ug/L) Standard Error 1.04	13.8 Micrograms per Liter (ug/L) Standard Error 1.14
Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 144 CTX-1, Week 144, n=281, 296	0.0750 Micrograms per Liter (ug/L) Standard Error 0.01150	0.2164 Micrograms per Liter (ug/L) Standard Error 0.01407

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Weeks 24, 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood samples were collected to perform evaluation of bone biomarker serum vitamin D. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Bone Biomarker-Serum Vitamin D at Weeks 24, 48 Serum Vitamin D, Week 24, n=337, 337	5.9 Nanomoles per Liter (nmol/L) Standard Error 1.15	12.4 Nanomoles per Liter (nmol/L) Standard Error 1.33
Change From Baseline in Bone Biomarker-Serum Vitamin D at Weeks 24, 48 Serum Vitamin D, Week 48, n=322, 333	-3.1 Nanomoles per Liter (nmol/L) Standard Error 0.89	3.1 Nanomoles per Liter (nmol/L) Standard Error 1.10

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of bone biomarker serum vitamin D. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=298 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=320 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Bone Biomarker-Serum Vitamin D at Week 96	-2.2 Nanomoles per Liter (nmol/L) Standard Error 1.05	0.7 Nanomoles per Liter (nmol/L) Standard Error 1.04

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of bone biomarker serum vitamin D. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=281 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=298 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Bone Biomarker-Serum Vitamin D at Week 144	-2.0 Nanomoles per Liter (nmol/L) Standard Error 1.16	2.9 Nanomoles per Liter (nmol/L) Standard Error 1.28

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Weeks 24, 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value is defined as the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value).

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 Serum or Plasma Cholesterol, Week 24, n=294, 297	9.4 Percentage change Standard Deviation 17.44	-4.7 Percentage change Standard Deviation 16.12
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 Serum or Plasma Cholesterol, Week 48, n=280, 289	10.5 Percentage change Standard Deviation 18.89	-2.4 Percentage change Standard Deviation 17.14
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 HDL Cholesterol, Direct, Week 24, n=294, 297	16.4 Percentage change Standard Deviation 22.58	3.4 Percentage change Standard Deviation 21.55
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 HDL Cholesterol, Direct, Week 48, n=280, 289	15.0 Percentage change Standard Deviation 25.07	5.0 Percentage change Standard Deviation 33.04
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 LDL Cholesterol, Week 24, n=294, 297	12.4 Percentage change Standard Deviation 45.05	-8.1 Percentage change Standard Deviation 23.70
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 LDL Cholesterol, Week 48, n=280, 289	14.8 Percentage change Standard Deviation 48.74	-4.0 Percentage change Standard Deviation 24.06
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 Triglycerides ,Week 24, n=294, 297	8.5 Percentage change Standard Deviation 46.57	4.3 Percentage change Standard Deviation 72.35
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 Triglycerides , Week 48, n=280, 289	12.8 Percentage change Standard Deviation 68.99	4.4 Percentage change Standard Deviation 70.43

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed

Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=253 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=277 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 96 Serum or Plasma Cholesterol, Week 96	0.379 Millimoles per liter Standard Error 0.0376	-0.104 Millimoles per liter Standard Error 0.0378
Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 96 HDL Cholesterol, Direct, Week 96	0.199 Millimoles per liter Standard Error 0.0156	0.090 Millimoles per liter Standard Error 0.0149
Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 96 LDL Cholesterol, Week 96,	0.147 Millimoles per liter Standard Error 0.0338	-0.154 Millimoles per liter Standard Error 0.0303
Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 96 Triglycerides, Week 96,	0.129 Millimoles per liter Standard Error 0.0835	-0.112 Millimoles per liter Standard Error 0.0358

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed

Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=245 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=256 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 144 LDL Cholesterol, Week 144,	0.170 Millimoles per liter Standard Error 0.0336	-0.105 Millimoles per liter Standard Error 0.0348
Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 144 Serum or Plasma Cholesterol, Week 144,	0.367 Millimoles per liter Standard Error 0.0408	-0.037 Millimoles per liter Standard Error 0.0406
Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 144 HDL Cholesterol, Direct, Week 144	0.181 Millimoles per liter Standard Error 0.0150	0.098 Millimoles per liter Standard Error 0.0147
Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 144 Triglycerides, Week 144	0.117 Millimoles per liter Standard Error 0.0872	-0.104 Millimoles per liter Standard Error 0.0385

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Weeks 24, 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value is the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value).

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48 Total/HDL Cholesterol Ratio, Week 24, n=294, 297	-4.0 Percentage change Standard Deviation 19.08	-4.6 Percentage change Standard Deviation 27.52
Percentage Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48 Total/HDL Cholesterol Ratio, Week 48, n=280, 289	-0.2 Percentage change Standard Deviation 31.10	-4.4 Percentage change Standard Deviation 16.96

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=253 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=277 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Week 96	-0.213 Ratio Standard Error 0.0566	-0.402 Ratio Standard Error 0.0479

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=245 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=256 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Week 144	-0.229 Ratio Standard Error 0.0559	-0.386 Ratio Standard Error 0.0463

SECONDARY outcome

Timeframe: Weeks 24 and Week 48

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Blood samples were collected to perform evaluation of fasting LDL cholesterol. Any abnormalities were evaluated by the investigator and graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24 and 48 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 48 or those who had Baseline lipids-lowering agents are not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48 Week 24, n=309, 316	4 Percentage of participants	2 Percentage of participants
Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48 Week 48, n=318, 320	4 Percentage of participants	3 Percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of fasting LDL cholesterol. Any abnormalities were evaluated by the investigator and graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Week 96 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 96 or those who had Baseline lipids-lowering agents were not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=320 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=323 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Week 96	5 Percentage of participants	4 Percentage of participants

SECONDARY outcome

Timeframe: Week 144

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Blood samples were collected to perform evaluation of fasting LDL cholesterol. Any abnormalities were evaluated by the investigator and graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Week 144 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 144 or those who had Baseline lipids-lowering agents were not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=321 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=322 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Week 144	5 Percentage of participants	4 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian, Other). Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Baseline CD4+ cell count, <=200,n=31,29	90 Percentage of participants	86 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Baseline CD4+ cell count, >200,n=325,329	93 Percentage of participants	94 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Female, n=59, 52	93 Percentage of participants	96 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Male, n=297, 306	92 Percentage of participants	92 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Age, <35,n= 211, 205	93 Percentage of participants	95 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Age, 35 to <50,n=116, 107	91 Percentage of participants	93 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Age, >=50, n=29, 46	93 Percentage of participants	85 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Baseline plasma HIV-1 RNA, <=100000,n=282,282	93 Percentage of participants	95 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Baseline plasma HIV-1 RNA, >100000,n=74, 76	92 Percentage of participants	87 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Race, White, n=244,247	93 Percentage of participants	95 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Race, African American/African H., n=39, 36	92 Percentage of participants	81 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Race, Asian, n=37, 42	89 Percentage of participants	93 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 Race, Other, n=36, 33	94 Percentage of participants	94 Percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian, Other). Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Baseline CD4+ cell count, <=200,n=31,29	81 Percentage of participants	90 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Baseline CD4+ cell count, >200,n=325,329	91 Percentage of participants	93 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Female, n=59, 52	88 Percentage of participants	94 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Male, n=297, 306	90 Percentage of participants	92 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Age, <35,n= 211, 205	92 Percentage of participants	93 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Age, 35 to <50,n=116, 107	86 Percentage of participants	94 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Age, >=50, n=29, 46	90 Percentage of participants	87 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Baseline plasma HIV-1 RNA, <=100000,n=282,282	90 Percentage of participants	93 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Baseline plasma HIV-1 RNA, >100000,n=74, 76	88 Percentage of participants	91 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Race, White, n=244,247	90 Percentage of participants	94 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Race, African American/African H., n=39, 36	87 Percentage of participants	81 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Race, Asian, n=37, 42	92 Percentage of participants	98 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 Race, Other, n=36, 33	89 Percentage of participants	94 Percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm^3, >200 cells/mm^3), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian and other). Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Baseline CD4+ cell count, <=200,n=31, 29	65 Percentage of participants	90 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Baseline CD4+ cell count, >200,n=325,329	86 Percentage of participants	89 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Female, n=59, 52	83 Percentage of participants	88 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Male, n=297,306,	85 Percentage of participants	90 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Age, <35,n= 211, 205	84 Percentage of participants	90 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Age, 35 to <50,n=116, 107	84 Percentage of participants	89 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Age, >=50, n=29,46	86 Percentage of participants	87 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Baseline plasma HIV-1 RNA, <=100000,n=282,282	85 Percentage of participants	90 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Baseline plasma HIV-1 RNA, >100000,n=74, 76	81 Percentage of participants	88 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Race, White, n=244,247	86 Percentage of participants	90 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Race, African American/African H., n=39,36	79 Percentage of participants	81 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Race, Asian, n=37, 42	78 Percentage of participants	90 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 Race, Other, n=36, 33	86 Percentage of participants	91 Percentage of participants

SECONDARY outcome

Timeframe: Week 144

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm^3, >200 cells/mm^3), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian and other). Percentage values are rounded to the nearest whole digit.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Baseline CD4+ cell count, <=200,n=31, 29	58 Percentage of participants	83 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Baseline CD4+ cell count, >200,n=325,329	81 Percentage of participants	83 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Female, n=59, 52	71 Percentage of participants	85 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Male, n=297,306,	80 Percentage of participants	82 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Age, <35,n= 211, 205	77 Percentage of participants	83 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Age, 35 to <50,n=116, 107	81 Percentage of participants	83 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Age, >=50, n=29,46	83 Percentage of participants	78 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Baseline plasma HIV-1 RNA, <=100000,n=282,282	79 Percentage of participants	82 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Baseline plasma HIV-1 RNA, >100000,n=74, 76	78 Percentage of participants	87 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Race, White, n=244,247	82 Percentage of participants	85 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Race, African American/African H., n=39,36	69 Percentage of participants	72 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Race, Asian, n=37, 42	73 Percentage of participants	81 Percentage of participants
Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 Race, Other, n=36, 33	78 Percentage of participants	79 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age, Gender, and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Baseline plasma HIV-1 RNA,<=100000, n=268,268	187.72 Cells per cubic millimeter Standard Error 10.860	167.93 Cells per cubic millimeter Standard Error 10.842
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Baseline plasma HIV-1 RNA,>100000, n=72,73	206.63 Cells per cubic millimeter Standard Error 21.107	205.96 Cells per cubic millimeter Standard Error 20.990
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Baseline CD4+ cell count,<=200, n=29,27	157.01 Cells per cubic millimeter Standard Error 33.113	120.17 Cells per cubic millimeter Standard Error 34.151
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Baseline CD4+ cell count,>200, n=311, 314	195.11 Cells per cubic millimeter Standard Error 10.026	180.73 Cells per cubic millimeter Standard Error 9.972
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Age, <35,n= 203,199	202.76 Cells per cubic millimeter Standard Error 12.456	177.62 Cells per cubic millimeter Standard Error 12.563
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Age, 35 to <50, n=109, 100	172.05 Cells per cubic millimeter Standard Error 16.983	179.87 Cells per cubic millimeter Standard Error 17.733
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Age, >=50, n=28, 42	188.79 Cells per cubic millimeter Standard Error 33.534	159.34 Cells per cubic millimeter Standard Error 27.344
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Female, n=57,50	199.45 Cells per cubic millimeter Standard Error 23.498	181.78 Cells per cubic millimeter Standard Error 25.263
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Male, n=283,291	190.21 Cells per cubic millimeter Standard Error 10.538	175.05 Cells per cubic millimeter Standard Error 10.400
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Race, White, n=236,235	204.78 Cells per cubic millimeter Standard Error 11.531	182.27 Cells per cubic millimeter Standard Error 11.582
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Race, African Am/African H., n=36,33	143.84 Cells per cubic millimeter Standard Error 29.541	170.51 Cells per cubic millimeter Standard Error 30.870
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Race, Asian, n=34, 41	169.80 Cells per cubic millimeter Standard Error 30.491	165.36 Cells per cubic millimeter Standard Error 27.782
Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups Race, Other, n=34,32	174.30 Cells per cubic millimeter Standard Error 30.375	149.34 Cells per cubic millimeter Standard Error 31.404

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 48

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from Analysis of Covariance (ANCOVA) model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Baseline plasma HIV-1 RNA,<=100000, n=257,264	220.0 Cells per cubic millimeter Standard Error 11.72	212.4 Cells per cubic millimeter Standard Error 11.56
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Baseline plasma HIV-1 RNA,>100000, n=67,70	238.5 Cells per cubic millimeter Standard Error 23.09	235.5 Cells per cubic millimeter Standard Error 22.70
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Baseline CD4+ cell count,<=200, n=26, 27	200.5 Cells per cubic millimeter Standard Error 36.97	177.9 Cells per cubic millimeter Standard Error 36.18
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Baseline CD4+ cell count,>200, n=298, 307	225.9 Cells per cubic millimeter Standard Error 10.84	220.7 Cells per cubic millimeter Standard Error 10.68
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Age group-1, <35,n= 194, 192	233.6 Cells per cubic millimeter Standard Error 13.49	225.2 Cells per cubic millimeter Standard Error 13.53
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Age group-1, 35 to <50, n=104, 101	208.7 Cells per cubic millimeter Standard Error 18.40	211.2 Cells per cubic millimeter Standard Error 18.67
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Age group-1, >=50, n=26, 41	212.6 Cells per cubic millimeter Standard Error 36.84	194.8 Cells per cubic millimeter Standard Error 29.27
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Female, n=54, 49	237.1 Cells per cubic millimeter Standard Error 25.53	226.8 Cells per cubic millimeter Standard Error 26.98
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Male, n=270, 285	221.2 Cells per cubic millimeter Standard Error 11.41	215.6 Cells per cubic millimeter Standard Error 11.11
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Race, White, n=224, 231	226.0 Cells per cubic millimeter Standard Error 12.55	219.7 Cells per cubic millimeter Standard Error 12.39
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Race, African Am/African H., n=33, 31	209.4 Cells per cubic millimeter Standard Error 32.75	239.9 Cells per cubic millimeter Standard Error 33.79
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Race, Asian, n=34, 41	246.4 Cells per cubic millimeter Standard Error 32.35	197.2 Cells per cubic millimeter Standard Error 29.47
Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups Race, Other, n=33, 31	200.2 Cells per cubic millimeter Standard Error 32.69	202.7 Cells per cubic millimeter Standard Error 33.83

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 96

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is the the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Baseline plasma HIV-1 RNA,<=100000, n=240,253	254.8 Cells per cubic millimeter Standard Error 13.30	252.9 Cells per cubic millimeter Standard Error 12.93
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Baseline plasma HIV-1 RNA,>100000, n=61,67	300.2 Cells per cubic millimeter Standard Error 26.50	260.1 Cells per cubic millimeter Standard Error 25.42
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Baseline CD4+ cell count,<=200, n=21,26	240.5 Cells per cubic millimeter Standard Error 45.16	244.4 Cells per cubic millimeter Standard Error 40.44
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Baseline CD4+ cell count,>200, n=280,294	265.9 Cells per cubic millimeter Standard Error 12.28	255.1 Cells per cubic millimeter Standard Error 11.98
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Age group-1, <35,n= 179,185	270.2 Cells per cubic millimeter Standard Error 15.38	263.0 Cells per cubic millimeter Standard Error 15.09
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Age group-1, 35 to <50, n=97,95	259.5 Cells per cubic millimeter Standard Error 20.86	262.0 Cells per cubic millimeter Standard Error 21.09
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Age group-1, >=50, n=25, 40	237.6 Cells per cubic millimeter Standard Error 41.11	195.9 Cells per cubic millimeter Standard Error 32.45
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Female, n=49,46	277.9 Cells per cubic millimeter Standard Error 29.40	259.1 Cells per cubic millimeter Standard Error 30.54
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Male, n=252, 274	261.4 Cells per cubic millimeter Standard Error 12.95	253.5 Cells per cubic millimeter Standard Error 12.43
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Race group, White, n=210,223	275.2 Cells per cubic millimeter Standard Error 14.21	260.0 Cells per cubic millimeter Standard Error 13.80
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Race group, African Am/African H., n=31,29	228.5 Cells per cubic millimeter Standard Error 37.07	230.2 Cells per cubic millimeter Standard Error 38.23
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Race group, Asian, n=29,38	212.1 Cells per cubic millimeter Standard Error 38.34	244.8 Cells per cubic millimeter Standard Error 33.53
Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups Race group, Other, n=31,30	273.4 Cells per cubic millimeter Standard Error 36.97	247.3 Cells per cubic millimeter Standard Error 37.67

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 144

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is the the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Baseline plasma HIV-1 RNA,<=100000, n=214,223	295.7 Cells per cubic millimeter Standard Error 14.14	296.1 Cells per cubic millimeter Standard Error 13.84
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Baseline plasma HIV-1 RNA,>100000, n=56, 64	334.3 Cells per cubic millimeter Standard Error 27.77	329.6 Cells per cubic millimeter Standard Error 26.15
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Baseline CD4+ cell count,<=200, n=17, 24	290.2 Cells per cubic millimeter Standard Error 50.44	272.9 Cells per cubic millimeter Standard Error 42.29
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Baseline CD4+ cell count,>200, n=253, 263	304.7 Cells per cubic millimeter Standard Error 12.97	306.2 Cells per cubic millimeter Standard Error 12.71
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Age group, <35,n=155, 167	298.0 Cells per cubic millimeter Standard Error 16.59	316.0 Cells per cubic millimeter Standard Error 15.93
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Age group-1, 35 to <50, n=92, 87	305.6 Cells per cubic millimeter Standard Error 21.48	302.1 Cells per cubic millimeter Standard Error 22.11
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Age group-1, >=50, n=23,33	337.4 Cells per cubic millimeter Standard Error 43.01	242.2 Cells per cubic millimeter Standard Error 35.83
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Female, n=43, 43	346.6 Cells per cubic millimeter Standard Error 31.40	321.7 Cells per cubic millimeter Standard Error 31.67
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Male, n=227, 244	295.9 Cells per cubic millimeter Standard Error 13.66	300.0 Cells per cubic millimeter Standard Error 13.20
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Race group, White, n=190,201	314.2 Cells per cubic millimeter Standard Error 14.93	314.0 Cells per cubic millimeter Standard Error 14.53
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Race group, African Am/African H., n=26, 26	243.8 Cells per cubic millimeter Standard Error 40.42	295.1 Cells per cubic millimeter Standard Error 40.39
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Race group, Asian, n=26, 34	244.0 Cells per cubic millimeter Standard Error 40.47	264.1 Cells per cubic millimeter Standard Error 35.41
Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups Race group, Other, n=28,26	346.2 Cells per cubic millimeter Standard Error 38.87	279.9 Cells per cubic millimeter Standard Error 40.42

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 4, 24, 48

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has 1 question assessing each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. Baseline was the latest pre-dose assessment (Day 1) and change from Baseline=post-dose value minus Baseline value.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Utility Score at Weeks 4, 24, 48 Week 4, n=349, 348	0.0130 Scores on a scale Standard Error 0.00362	0.0078 Scores on a scale Standard Error 0.00353
Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Utility Score at Weeks 4, 24, 48 Week 24, n=352, 351	0.0131 Scores on a scale Standard Error 0.00371	0.0168 Scores on a scale Standard Error 0.00333
Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Utility Score at Weeks 4, 24, 48 Week 48, n=352, 351	0.0134 Scores on a scale Standard Error 0.00384	0.0129 Scores on a scale Standard Error 0.00349

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 96

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has 1 question assessing each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. Baseline was the latest pre-dose assessment (Day 1) and change from Baseline=post-dose value minus Baseline value.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=352 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=351 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in EQ-5D-5L Utility Score at Week 96	0.0079 Scores on a scale Standard Error 0.00450	0.0091 Scores on a scale Standard Error 0.00408

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 144

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has 1 question assessing each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. Baseline was the latest pre-dose assessment (Day 1) and change from Baseline=post-dose value minus Baseline value.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=352 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=351 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in EQ-5D-5L Utility Score at Week 144	0.0143 Scores on a scale Standard Error 0.00388	0.0135 Scores on a scale Standard Error 0.00365

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 4, 24, 48

Population: ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=356 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=358 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48 Week 4, n=349, 348	2.3 Scores on a scale Standard Error 0.48	1.2 Scores on a scale Standard Error 0.52
Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48 Week 24, n=352, 350	3.7 Scores on a scale Standard Error 0.54	3.2 Scores on a scale Standard Error 0.51
Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48 Week 48, n=352, 350	4.3 Scores on a scale Standard Error 0.49	2.8 Scores on a scale Standard Error 0.49

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 96

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

EQ-5D-5L questionnaire provided a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value. Adjusted mean and standard error is presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=352 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=350 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in EQ-5D-5L Thermometer Scores at Week 96	4.1 Scores on a scale Standard Error 0.51	2.4 Scores on a scale Standard Error 0.56

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 144

Population: ITT-E Population. Only those participants available at the specified time points were analyzed.

EQ-5D-5L questionnaire provided a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value. Adjusted mean and standard error is presented.

Outcome measures

Measure	DTG + 3TC-Double Blind Phase n=352 Participants Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase	DTG + TDF/FTC-Double Blind Phase n=350 Participants Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 96 weeks in the double blind phase.
Change From Baseline in EQ-5D-5L Thermometer Scores at Week 144	5.2 Scores on a scale Standard Error 0.48	3.0 Scores on a scale Standard Error 0.50

Adverse Events

DTG + 3TC-Double-blind Phase + Open-label Phase

Serious events: 37 serious events

Other events: 272 other events

Deaths: 1 deaths

DTG + TDF/FTC-Double-blind Phase + Open-label Phase

Serious events: 38 serious events

Other events: 268 other events

Deaths: 0 deaths

DTG + 3TC-Continuation Phase

Serious events: 5 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Measure	DTG + 3TC-Double-blind Phase + Open-label Phase n=356 participants at risk Participants received a two-drug regimen of DTG + 3TC administered orally, once daily until Week 96 in double-blind phase and participants continued to receive DTG + 3TC from Week 96 to Week 148 in the open-label phase.	DTG + TDF/FTC-Double-blind Phase + Open-label Phase n=358 participants at risk Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily until Week 96 in double-blind phase and participants continued to receive DTG + TDF/FTC FDC from Week 96 to Week 148 in the open-label phase.	DTG + 3TC-Continuation Phase n=233 participants at risk Participants received a DTG + 3TC administered orally, once daily from Week 148 to Week 280 in the continuation phase.
Psychiatric disorders Psychotic disorder	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Hepatitis A	0.84% 3/356 • Number of events 3 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	1.1% 4/358 • Number of events 4 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.43% 1/233 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Appendicitis	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	1.1% 4/358 • Number of events 4 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.86% 2/233 • Number of events 2 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Injury, poisoning and procedural complications Head injury	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.43% 1/233 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Pneumonia	0.56% 2/356 • Number of events 2 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.56% 2/358 • Number of events 2 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Abscess limb	0.56% 2/356 • Number of events 2 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Acute hepatitis C	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Anal abscess	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anogenital warts	0.56% 2/356 • Number of events 2 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Bacterial infection	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Cellulitis	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.56% 2/358 • Number of events 2 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Chagoma	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Hepatobiliary disorders Cholecystitis acute	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Hepatobiliary disorders Cholelithiasis	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clear cell renal cell carcinoma	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Cardiac disorders Coronary artery stenosis	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Gastric ulcer haemorrhage	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Gastroenteritis	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Helicobacter gastritis	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Hepatobiliary disorders Hepatitis toxic	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Herpes zoster	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Intestinal obstruction	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Injury, poisoning and procedural complications Joint dislocation	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Lower respiratory tract infection	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Psychiatric disorders Major depression	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Perineal abscess	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Nervous system disorders Polyneuropathy	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Injury, poisoning and procedural complications Post lumbar puncture syndrome	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Psychiatric disorders Substance-induced psychotic disorder	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Psychiatric disorders Suicide attempt	0.84% 3/356 • Number of events 3 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Appendicitis perforated	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Encephalitis	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Peritonitis	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Erysipelas	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Urinary tract infection	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Injury, poisoning and procedural complications Jaw fracture	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Injury, poisoning and procedural complications Multiple injuries	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.43% 1/233 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease	0.56% 2/356 • Number of events 2 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Respiratory, thoracic and mediastinal disorders Pulmonary sarcoidosis	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Cardiac disorders Acute myocardial infarction	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Cardiac disorders Cardiac failure	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Cardiac disorders Coronary artery disease	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Anal fistula	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Colitis	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Psychiatric disorders Delirium	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Psychiatric disorders Suicidal ideation	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Psychiatric disorders Bipolar I disorder	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 2 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
General disorders Chest pain	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
General disorders Non-cardiac chest pain	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Musculoskeletal and connective tissue disorders Arthritis reactive	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Nervous system disorders Syncope	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Nervous system disorders Acute polyneuropathy	0.28% 1/356 • Number of events 1 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Renal and urinary disorders Nephrolithiasis	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.84% 3/358 • Number of events 3 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Vascular disorders Varicose vein	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.28% 1/358 • Number of events 2 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase

Other adverse events

Measure	DTG + 3TC-Double-blind Phase + Open-label Phase n=356 participants at risk Participants received a two-drug regimen of DTG + 3TC administered orally, once daily until Week 96 in double-blind phase and participants continued to receive DTG + 3TC from Week 96 to Week 148 in the open-label phase.	DTG + TDF/FTC-Double-blind Phase + Open-label Phase n=358 participants at risk Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily until Week 96 in double-blind phase and participants continued to receive DTG + TDF/FTC FDC from Week 96 to Week 148 in the open-label phase.	DTG + 3TC-Continuation Phase n=233 participants at risk Participants received a DTG + 3TC administered orally, once daily from Week 148 to Week 280 in the continuation phase.
Nervous system disorders Headache	14.3% 51/356 • Number of events 80 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	13.1% 47/358 • Number of events 82 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.0% 7/233 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Diarrhoea	14.0% 50/356 • Number of events 69 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	14.8% 53/358 • Number of events 73 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Nasopharyngitis	13.8% 49/356 • Number of events 74 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	16.2% 58/358 • Number of events 84 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.0% 7/233 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Upper respiratory tract infection	10.4% 37/356 • Number of events 50 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	9.2% 33/358 • Number of events 41 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.0% 7/233 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Psychiatric disorders Insomnia	8.1% 29/356 • Number of events 33 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	10.1% 36/358 • Number of events 40 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Nausea	3.7% 13/356 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	8.9% 32/358 • Number of events 37 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Musculoskeletal and connective tissue disorders Back pain	6.2% 22/356 • Number of events 31 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	7.0% 25/358 • Number of events 28 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Pharyngitis	10.7% 38/356 • Number of events 49 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	8.4% 30/358 • Number of events 43 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.6% 6/233 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Syphilis	10.7% 38/356 • Number of events 45 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	11.2% 40/358 • Number of events 47 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.6% 6/233 • Number of events 6 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Bronchitis	8.4% 30/356 • Number of events 36 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	5.9% 21/358 • Number of events 23 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
General disorders Pyrexia	5.1% 18/356 • Number of events 24 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.4% 12/358 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
General disorders Fatigue	4.5% 16/356 • Number of events 19 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.9% 14/358 • Number of events 15 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Influenza	6.7% 24/356 • Number of events 28 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	5.0% 18/358 • Number of events 20 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
General disorders Influenza like illness	5.3% 19/356 • Number of events 20 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	4.5% 16/358 • Number of events 25 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Respiratory, thoracic and mediastinal disorders Cough	3.7% 13/356 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	5.3% 19/358 • Number of events 19 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Sinusitis	4.2% 15/356 • Number of events 17 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	4.2% 15/358 • Number of events 20 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Abdominal pain	4.5% 16/356 • Number of events 16 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	4.5% 16/358 • Number of events 19 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Gastroenteritis	4.8% 17/356 • Number of events 19 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	4.2% 15/358 • Number of events 15 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anogenital warts	3.9% 14/356 • Number of events 14 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	4.7% 17/358 • Number of events 19 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Psychiatric disorders Depression	5.1% 18/356 • Number of events 20 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	4.7% 17/358 • Number of events 18 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Gonorrhoea	4.5% 16/356 • Number of events 22 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.6% 13/358 • Number of events 18 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.4% 12/356 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	4.2% 15/358 • Number of events 15 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Tonsillitis	3.7% 13/356 • Number of events 15 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.4% 12/358 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Nervous system disorders Dizziness	2.8% 10/356 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.8% 10/358 • Number of events 10 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 7/356 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	6.1% 22/358 • Number of events 24 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Herpes zoster	2.2% 8/356 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.6% 13/358 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Vascular disorders Hypertension	4.5% 16/356 • Number of events 18 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.9% 14/358 • Number of events 14 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.1% 5/233 • Number of events 9 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Dyspepsia	3.7% 13/356 • Number of events 20 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.4% 12/358 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Haemorrhoids	5.9% 21/356 • Number of events 25 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	4.5% 16/358 • Number of events 17 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Psychiatric disorders Anxiety	5.3% 19/356 • Number of events 24 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	4.2% 15/358 • Number of events 18 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Pharyngotonsillitis	4.2% 15/356 • Number of events 26 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.4% 12/358 • Number of events 18 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Respiratory tract infection	2.5% 9/356 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.8% 10/358 • Number of events 19 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Respiratory tract infection viral	2.2% 8/356 • Number of events 10 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.5% 9/358 • Number of events 15 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Metabolism and nutrition disorders Vitamin D deficiency	7.0% 25/356 • Number of events 25 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	6.1% 22/358 • Number of events 23 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Abdominal pain upper	1.7% 6/356 • Number of events 9 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.8% 10/358 • Number of events 12 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	4.2% 15/356 • Number of events 24 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	1.4% 5/358 • Number of events 5 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Vomiting	3.1% 11/356 • Number of events 12 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.5% 9/358 • Number of events 10 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Gastritis	2.8% 10/356 • Number of events 11 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	1.7% 6/358 • Number of events 6 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Toothache	3.1% 11/356 • Number of events 15 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.5% 9/358 • Number of events 11 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Gastrointestinal disorders Gastrooesophageal reflux disease	2.8% 10/356 • Number of events 10 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.0% 7/358 • Number of events 7 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Chlamydial infection	3.9% 14/356 • Number of events 15 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.8% 10/358 • Number of events 10 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Urethritis	2.5% 9/356 • Number of events 11 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.6% 13/358 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Urinary tract infection	2.5% 9/356 • Number of events 11 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.6% 13/358 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Oropharyngeal gonococcal infection	2.2% 8/356 • Number of events 9 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.0% 7/358 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Tooth infection	2.8% 10/356 • Number of events 10 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.0% 7/358 • Number of events 7 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Acute sinusitis	1.1% 4/356 • Number of events 4 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.2% 8/358 • Number of events 9 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Oral herpes	2.5% 9/356 • Number of events 11 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.2% 8/358 • Number of events 9 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Proctitis gonococcal	2.2% 8/356 • Number of events 12 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.5% 9/358 • Number of events 12 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Anal chlamydia infection	2.5% 9/356 • Number of events 16 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	1.4% 5/358 • Number of events 5 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Conjunctivitis	2.2% 8/356 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	1.7% 6/358 • Number of events 6 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations COVID-19	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	6.9% 16/233 • Number of events 18 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Infections and infestations Suspected COVID-19	0.00% 0/356 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/358 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	3.4% 8/233 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Musculoskeletal and connective tissue disorders Myalgia	1.4% 5/356 • Number of events 6 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.5% 9/358 • Number of events 9 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.1% 4/356 • Number of events 4 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.8% 10/358 • Number of events 11 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Musculoskeletal and connective tissue disorders Pain in extremity	2.2% 8/356 • Number of events 10 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	1.7% 6/358 • Number of events 6 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.84% 3/356 • Number of events 3 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.2% 8/358 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Respiratory, thoracic and mediastinal disorders Respiratory disorder	2.2% 8/356 • Number of events 11 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	1.4% 5/358 • Number of events 7 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Respiratory, thoracic and mediastinal disorders Asthma	2.2% 8/356 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.84% 3/358 • Number of events 3 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Skin and subcutaneous tissue disorders Rash	3.1% 11/356 • Number of events 11 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.2% 8/358 • Number of events 13 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Immune system disorders Seasonal allergy	2.2% 8/356 • Number of events 10 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.2% 8/358 • Number of events 12 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Skin and subcutaneous tissue disorders Pruritus	2.5% 9/356 • Number of events 9 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.0% 7/358 • Number of events 8 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase
Nervous system disorders Paraesthesia	1.1% 4/356 • Number of events 4 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	2.5% 9/358 • Number of events 10 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase	0.00% 0/233 • All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises all participants who received at least 1 dose of study treatment after entering the Continuation Phase

Additional Information

GSK Response Center

ViiV Healthcare

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Email: GSKClinicalSupportHD@gsk.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
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