Trial Outcomes & Findings for Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Elvitegravir Versus Raltegravir (NCT NCT00708162)

Last Updated: 2016-05-30

Results Overview

The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the FDA-defined Time to Loss of Virologic Response (TLOVR) algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

724 participants

Primary outcome timeframe

Week 48

Results posted on

2016-05-30

Participant Flow

Participants were enrolled in a total of 161 study sites in Australia, Europe, and North America. The first participant was screened on 19 June 2008. The last study visit occurred on 22 April 2015.

1335 participants were screened.

Participant milestones

Participant milestones
Measure	Elvitegravir Elvitegravir (EVG) 85 or 150 mg tablet once daily plus raltegravir (RAL) placebo plus background regimen (1 fully-active ritonavir (RTV)-boosted protease inhibitor (PI) plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Randomized Phase STARTED	361	363
Randomized Phase Randomized and Treated	354	358
Randomized Phase COMPLETED	205	209
Randomized Phase NOT COMPLETED	156	154
Open-Label Phase STARTED	196	151
Open-Label Phase COMPLETED	152	121
Open-Label Phase NOT COMPLETED	44	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Elvitegravir Elvitegravir (EVG) 85 or 150 mg tablet once daily plus raltegravir (RAL) placebo plus background regimen (1 fully-active ritonavir (RTV)-boosted protease inhibitor (PI) plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Randomized Phase Randomized but Not Treated	7	5
Randomized Phase Participant Noncompliance	40	32
Randomized Phase Lost to Follow-up	34	34
Randomized Phase Withdrew Consent	31	22
Randomized Phase Lack of Efficacy	14	19
Randomized Phase Protocol Violation	10	11
Randomized Phase Adverse Event	8	12
Randomized Phase Investigator's Discretion	7	10
Randomized Phase Death	2	9
Randomized Phase Pregnancy	3	0
Open-Label Phase Lost to Follow-up	10	8
Open-Label Phase Withdrew Consent	12	6
Open-Label Phase Participant Noncompliance	7	7
Open-Label Phase Lack of Efficacy	7	4
Open-Label Phase Investigator's Discretion	3	2
Open-Label Phase Death	3	1
Open-Label Phase Adverse Event	1	2
Open-Label Phase Other	1	0

Baseline Characteristics

Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Elvitegravir Versus Raltegravir

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Elvitegravir n=354 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=358 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Total n=712 Participants Total of all reporting groups
Age, Continuous	44 years STANDARD_DEVIATION 9.0 • n=5 Participants	45 years STANDARD_DEVIATION 9.1 • n=7 Participants	45 years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	67 Participants n=7 Participants	127 Participants n=5 Participants
Sex: Female, Male Male	294 Participants n=5 Participants	291 Participants n=7 Participants	585 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	81 Participants n=5 Participants	74 Participants n=7 Participants	155 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	272 Participants n=5 Participants	283 Participants n=7 Participants	555 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	210 participants n=5 Participants	227 participants n=7 Participants	437 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	128 participants n=5 Participants	119 participants n=7 Participants	247 participants n=5 Participants
Race/Ethnicity, Customized Asian	9 participants n=5 Participants	5 participants n=7 Participants	14 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment United States	230 participants n=5 Participants	223 participants n=7 Participants	453 participants n=5 Participants
Region of Enrollment Portugal	10 participants n=5 Participants	11 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment Spain	14 participants n=5 Participants	20 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment United Kingdom	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Italy	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment France	16 participants n=5 Participants	9 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Mexico	26 participants n=5 Participants	25 participants n=7 Participants	51 participants n=5 Participants
Region of Enrollment Canada	16 participants n=5 Participants	18 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Puerto Rico	8 participants n=5 Participants	14 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Belgium	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Australia	17 participants n=5 Participants	12 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Germany	6 participants n=5 Participants	8 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Netherlands	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
HIV-1 RNA	4.26 log10 copies/mL STANDARD_DEVIATION 0.969 • n=5 Participants	4.27 log10 copies/mL STANDARD_DEVIATION 0.943 • n=7 Participants	4.26 log10 copies/mL STANDARD_DEVIATION 0.955 • n=5 Participants
HIV-1 RNA category ≤ 100,000 copies/mL	263 participants n=5 Participants	267 participants n=7 Participants	530 participants n=5 Participants
HIV-1 RNA category > 100,000 copies/mL	91 participants n=5 Participants	91 participants n=7 Participants	182 participants n=5 Participants
Cluster of differentiation (CD4) Cell Count	257.9 cells/mm^3 STANDARD_DEVIATION 204.31 • n=5 Participants	265.3 cells/mm^3 STANDARD_DEVIATION 207.04 • n=7 Participants	261.6 cells/mm^3 STANDARD_DEVIATION 205.57 • n=5 Participants
HIV Disease Status Asymptomatic	172 participants n=5 Participants	175 participants n=7 Participants	347 participants n=5 Participants
HIV Disease Status Symptomatic HIV Infections	52 participants n=5 Participants	54 participants n=7 Participants	106 participants n=5 Participants
HIV Disease Status AIDS	126 participants n=5 Participants	125 participants n=7 Participants	251 participants n=5 Participants
HIV Disease Status Unknown	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Type of PI in Background Regimen (Excluding Ritonavir) atazanavir	64 participants n=5 Participants	53 participants n=7 Participants	117 participants n=5 Participants
Type of PI in Background Regimen (Excluding Ritonavir) darunavir	202 participants n=5 Participants	206 participants n=7 Participants	408 participants n=5 Participants
Type of PI in Background Regimen (Excluding Ritonavir) fosamprenavir	14 participants n=5 Participants	20 participants n=7 Participants	34 participants n=5 Participants
Type of PI in Background Regimen (Excluding Ritonavir) lopinavir	68 participants n=5 Participants	72 participants n=7 Participants	140 participants n=5 Participants
Type of PI in Background Regimen (Excluding Ritonavir) tipranavir	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants
Type of NRTI in Background Regimen tenofovir disoproxil fumarate	163 participants n=5 Participants	171 participants n=7 Participants	334 participants n=5 Participants
Type of NRTI in Background Regimen emtricitabine/tenofovir disoproxil fumarate	91 participants n=5 Participants	66 participants n=7 Participants	157 participants n=5 Participants
Type of NRTI in Background Regimen lamivudine	13 participants n=5 Participants	13 participants n=7 Participants	26 participants n=5 Participants
Type of NRTI in Background Regimen abacavir	6 participants n=5 Participants	15 participants n=7 Participants	21 participants n=5 Participants
Type of NRTI in Background Regimen abacavir/lamivudine	4 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants
Type of NRTI in Background Regimen lamivudine/zidovudine	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Type of NRTI in Background Regimen zidovudine	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Type of NRTI in Background Regimen didanosine	1 participants n=5 Participants	7 participants n=7 Participants	8 participants n=5 Participants
Type of NRTI in Background Regimen emtricitabine	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Type of NRTI in Background Regimen no NRTI in background regimen	65 participants n=5 Participants	64 participants n=7 Participants	129 participants n=5 Participants
Enfuvirtide (T-20) in background regimen No	352 participants n=5 Participants	357 participants n=7 Participants	709 participants n=5 Participants
Enfuvirtide (T-20) in background regimen Yes	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Etravirine in background regimen No	309 participants n=5 Participants	303 participants n=7 Participants	612 participants n=5 Participants
Etravirine in background regimen Yes	45 participants n=5 Participants	55 participants n=7 Participants	100 participants n=5 Participants
Maraviroc in background regimen No	330 participants n=5 Participants	340 participants n=7 Participants	670 participants n=5 Participants
Maraviroc in background regimen Yes	24 participants n=5 Participants	18 participants n=7 Participants	42 participants n=5 Participants
Phenotypic Sensitivity Score 1.0	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Phenotypic Sensitivity Score 1.5	23 participants n=5 Participants	28 participants n=7 Participants	51 participants n=5 Participants
Phenotypic Sensitivity Score 2.0	309 participants n=5 Participants	313 participants n=7 Participants	622 participants n=5 Participants
Phenotypic Sensitivity Score 2.5	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Phenotypic Sensitivity Score 3.0	14 participants n=5 Participants	10 participants n=7 Participants	24 participants n=5 Participants
Phenotypic Sensitivity Score 3.5	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Phenotypic Sensitivity Score No baseline PSS score	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Chronic Hepatitis B (HBV) Infection Status Indeterminant	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Chronic Hepatitis B (HBV) Infection Status Negative	333 participants n=5 Participants	342 participants n=7 Participants	675 participants n=5 Participants
Chronic Hepatitis B (HBV) Infection Status Positive	17 participants n=5 Participants	13 participants n=7 Participants	30 participants n=5 Participants
Chronic Hepatitis B (HBV) Infection Status No baseline HBV measurement	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Chronic Hepatitis C (HCV) Infection Status Indeterminant	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Chronic Hepatitis C (HCV) Infection Status Negative	305 participants n=5 Participants	298 participants n=7 Participants	603 participants n=5 Participants
Chronic Hepatitis C (HCV) Infection Status Positive	44 participants n=5 Participants	55 participants n=7 Participants	99 participants n=5 Participants
Chronic Hepatitis C (HCV) Infection Status No baseline HCV measurement	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: ITT Analysis Set

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48	59.0 percentage of participants	57.8 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: ITT Analysis Set

The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 96	47.6 percentage of participants	45.0 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: ITT Analysis Set

The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 48	68.1 percentage of participants	67.2 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: ITT Analysis Set

The percentage of participants achieving and maintaining confirmed HIV-1 RNA \< 400 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 96	57.0 percentage of participants	56.1 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: ITT Analysis Set

Virologic response at Week 48 (percentage of participants with HIV-1 RNA \< 50 copies/mL) was analyzed using the FDA-defined Snapshot algorithm, which defines a patient's virologic response status using the viral load along with study drug discontinuation status at the predefined time point within an allowed window of time.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Virologic Response at Week 48 (HIV-1 RNA < 50 Copies/mL)	59.8 percentage of participants	57.5 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: ITT Analysis Set

Virologic response at Week 96 (percentage of participants with HIV-1 RNA \< 50 copies/mL) was analyzed using the FDA-defined Snapshot algorithm, which defines a patient's virologic response status using the viral load along with study drug discontinuation status at the predefined time point within an allowed window of time.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Virologic Response at Week 96 (HIV-1 RNA < 50 Copies/mL)	52.4 percentage of participants	53.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: ITT Analysis Set

The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 50 copies/mL) up to Week 48 was estimated using the Kaplan-Meier method in the time to event analysis.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 48	35 percentage of participants Interval 29.8 to 39.8	35 percentage of participants Interval 29.8 to 39.8

SECONDARY outcome

Timeframe: Baseline to Week 96

Population: ITT Analysis Set

The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 50 copies/mL) up to Week 96 was estimated using the Kaplan-Meier method in the time to event analysis.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 96	45 percentage of participants Interval 39.3 to 49.9	46 percentage of participants Interval 41.1 to 51.9

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: ITT Analysis Set

The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 400 copies/mL) up to Week 48 was estimated using the Kaplan-Meier method in the time to event analysis.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 48	24 percentage of participants Interval 19.5 to 28.5	24 percentage of participants Interval 19.7 to 28.9

SECONDARY outcome

Timeframe: Baseline to Week 96

Population: ITT Analysis Set

The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 400 copies/mL) up to Week 96 was estimated using the Kaplan-Meier method in the time to event analysis.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 96	32 percentage of participants Interval 26.7 to 36.7	31 percentage of participants Interval 26.1 to 36.1

SECONDARY outcome

Timeframe: Week 48

Population: ITT Analysis Set

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the missing = failure method, where participants with missing data were considered as having failed to meet the criteria for evaluation.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48	61.0 percentage of participants	60.7 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: ITT Analysis Set

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the missing = failure method.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96	53.6 percentage of participants	56.4 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: ITT Analysis Set

The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the missing = failure method.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48	70.1 percentage of participants	72.1 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: ITT Analysis Set

The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 96 was analyzed using the missing = failure method.

Outcome measures

Outcome measures
Measure	Elvitegravir n=351 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=351 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96	61.3 percentage of participants	63.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: Participants in the ITT Analysis Set with evaluable change data at Week 48 were analyzed.

The change from baseline in log10 HIV-1 RNA (copies/mL) at Week 48 was analyzed.

Outcome measures

Outcome measures
Measure	Elvitegravir n=280 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=291 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Change From Baseline in HIV-1 RNA at Week 48	-2.17 log10 copies/mL Standard Deviation 1.162	-2.18 log10 copies/mL Standard Deviation 1.178

SECONDARY outcome

Timeframe: Baseline to Week 96

Population: Participants in the ITT Analysis Set with evaluable change data at Week 96 were analyzed.

The change from baseline in log10 HIV-1 RNA (copies/mL) at Week 96 was analyzed.

Outcome measures

Outcome measures
Measure	Elvitegravir n=238 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=238 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Change From Baseline in HIV-1 RNA at Week 96	-2.26 log10 copies/mL Standard Deviation 1.078	-2.31 log10 copies/mL Standard Deviation 1.068

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: Participants in the ITT Analysis Set with evaluable change data at Week 48 were analyzed.

The change from baseline in CD4 cell count (cells/mm\^3) at Week 48 was analyzed.

Outcome measures

Outcome measures
Measure	Elvitegravir n=267 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=282 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Change From Baseline in CD4 Cell Count at Week 48	138 cells/mm^3 Standard Deviation 141.4	147 cells/mm^3 Standard Deviation 148.9

SECONDARY outcome

Timeframe: Baseline to Week 96

Population: Participants in the ITT Analysis Set with evaluable change data at Week 96 were analyzed.

The change from baseline in CD4 cell count (cells/mm\^3) at Week 96 was analyzed.

Outcome measures

Outcome measures
Measure	Elvitegravir n=231 Participants EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=233 Participants RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Change From Baseline in CD4 Cell Count at Week 96	205 cells/mm^3 Standard Deviation 191.5	198 cells/mm^3 Standard Deviation 162.2

Adverse Events

Elvitegravir

Serious events: 73 serious events

Other events: 279 other events

Deaths: 0 deaths

Raltegravir

Serious events: 86 serious events

Other events: 250 other events

Deaths: 0 deaths

All Elvitegravir

Serious events: 127 serious events

Other events: 394 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosures

Gilead Sciences, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Elvitegravir n=354 participants at risk Adverse events in this reporting group are those experienced by participants in the Elvitegravir group during the Randomized Phase EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	Raltegravir n=358 participants at risk Adverse events in this reporting group are those experienced by participants in the Raltegravir group during the Randomized Phase RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.	All Elvitegravir n=505 participants at risk Adverse events in this reporting group are those experienced by participants in the Elvitegravir group during both the Randomized Phase and Open-Label Phase, and those experienced by participants in the Raltegravir group following switch to EVG in the Open-Label Phase only.
Gastrointestinal disorders Abdominal pain	6.8% 24/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.0% 18/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	7.9% 40/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Gastrointestinal disorders Diarrhoea	33.9% 120/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	21.5% 77/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	31.3% 158/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Gastrointestinal disorders Gastrooesophageal reflux disease	4.0% 14/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	2.5% 9/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.5% 28/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Gastrointestinal disorders Nausea	12.7% 45/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	11.5% 41/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	12.1% 61/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Gastrointestinal disorders Vomiting	6.2% 22/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	7.8% 28/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.9% 30/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
General disorders Fatigue	11.0% 39/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	7.0% 25/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	10.9% 55/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
General disorders Pyrexia	5.1% 18/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.3% 19/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.7% 29/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Infections and infestations Bronchitis	9.6% 34/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	9.5% 34/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	11.3% 57/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Infections and infestations Folliculitis	5.1% 18/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	2.0% 7/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.0% 25/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Infections and infestations Gastroenteritis	4.2% 15/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	2.0% 7/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.5% 28/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Infections and infestations Influenza	4.2% 15/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	2.8% 10/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.9% 30/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Infections and infestations Nasopharyngitis	11.3% 40/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	8.9% 32/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	11.1% 56/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Infections and infestations Oral herpes	4.2% 15/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	1.7% 6/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.1% 26/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Infections and infestations Sinusitis	7.9% 28/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	7.8% 28/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	9.5% 48/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Infections and infestations Upper respiratory tract infection	21.2% 75/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	16.5% 59/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	23.0% 116/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Infections and infestations Urinary tract infection	7.9% 28/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	9.8% 35/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	10.3% 52/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Metabolism and nutrition disorders Hypercholesterolaemia	3.4% 12/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.6% 20/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.1% 26/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Musculoskeletal and connective tissue disorders Arthralgia	8.5% 30/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	7.8% 28/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	11.3% 57/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Musculoskeletal and connective tissue disorders Back pain	11.9% 42/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	10.1% 36/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	13.5% 68/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Musculoskeletal and connective tissue disorders Muscle spasms	5.1% 18/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	3.6% 13/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.5% 28/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Musculoskeletal and connective tissue disorders Myalgia	4.0% 14/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	3.1% 11/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.1% 26/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Musculoskeletal and connective tissue disorders Pain in extremity	7.9% 28/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	7.0% 25/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	9.5% 48/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Nervous system disorders Headache	13.8% 49/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	10.3% 37/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	12.5% 63/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Psychiatric disorders Anxiety	4.5% 16/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	2.5% 9/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	6.5% 33/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Psychiatric disorders Depression	9.3% 33/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	9.2% 33/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	9.7% 49/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Psychiatric disorders Insomnia	7.3% 26/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	5.9% 21/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	8.3% 42/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Respiratory, thoracic and mediastinal disorders Cough	11.6% 41/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	13.1% 47/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	12.9% 65/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.1% 18/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	2.8% 10/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	4.8% 24/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Skin and subcutaneous tissue disorders Rash	7.9% 28/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	8.1% 29/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	7.9% 40/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug
Vascular disorders Hypertension	4.0% 14/354 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	7.3% 26/358 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug	7.7% 39/505 • Baseline through end of study drug treatment (average exposure: 100 weeks) plus 30 days Safety Analysis Set: participants who were randomized and received at least one dose of study drug