Trial Outcomes & Findings for Study to Evaluate Switching From a Regimen Consisting of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) Fixed Dose Combination (FDC) to Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) FDC in Virologically-Suppressed, HIV-1 Infected Adults (NCT NCT02345226)

Last Updated: 2020-01-02

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

881 participants

Primary outcome timeframe

Week 48

Results posted on

2020-01-02

Participant Flow

Participants were enrolled at study sites in Europe and North America. The first participant was screened on 26 January 2015. The last study visit occurred on 02 January 2019.

974 participants were screened.

Participant milestones

Participant milestones
Measure	FTC/RPV/TAF Double-Blind Phase: Emtricitabine/rilpivirine/tenofovir alafenamide (FTC/RPV/TAF) (200/25/25 mg) fixed-dose combination (FDC) tablet + efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) placebo tablet orally once daily for up to 96 weeks. Open-Label Extension Phase: After the Week 96 visit, participants were given the option to receive open label FTC/RPV/TAF FDC for up to an additional 48 weeks. In countries where FTC/RPV/TAF FDC was not yet commercially available, participants were given the option to receive open-label FTC/RPV/TAF FDC orally once daily and attend visits every 12 weeks until FTC/RPV/TAF FDC became commercially available, or until Gilead elected to discontinue the study, whichever occurred first.	EFV/FTC/TDF Double-Blind Phase: EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks. Open-Label Extension Phase: After the Week 96 visit, participants were given the option to receive open label FTC/RPV/TAF FDC for up to an additional 48 weeks. In countries where FTC/RPV/TAF FDC was not yet commercially available, participants were given the option to receive open-label FTC/RPV/TAF FDC orally once daily and attend visits every 12 weeks until FTC/RPV/TAF FDC became commercially available, or until Gilead elected to discontinue the study, whichever occurred first.
Double-Blind Phase STARTED	440	441
Double-Blind Phase COMPLETED	371	370
Double-Blind Phase NOT COMPLETED	69	71
Open-Label Extension Phase STARTED	25	21
Open-Label Extension Phase COMPLETED	25	20
Open-Label Extension Phase NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	FTC/RPV/TAF Double-Blind Phase: Emtricitabine/rilpivirine/tenofovir alafenamide (FTC/RPV/TAF) (200/25/25 mg) fixed-dose combination (FDC) tablet + efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) placebo tablet orally once daily for up to 96 weeks. Open-Label Extension Phase: After the Week 96 visit, participants were given the option to receive open label FTC/RPV/TAF FDC for up to an additional 48 weeks. In countries where FTC/RPV/TAF FDC was not yet commercially available, participants were given the option to receive open-label FTC/RPV/TAF FDC orally once daily and attend visits every 12 weeks until FTC/RPV/TAF FDC became commercially available, or until Gilead elected to discontinue the study, whichever occurred first.	EFV/FTC/TDF Double-Blind Phase: EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks. Open-Label Extension Phase: After the Week 96 visit, participants were given the option to receive open label FTC/RPV/TAF FDC for up to an additional 48 weeks. In countries where FTC/RPV/TAF FDC was not yet commercially available, participants were given the option to receive open-label FTC/RPV/TAF FDC orally once daily and attend visits every 12 weeks until FTC/RPV/TAF FDC became commercially available, or until Gilead elected to discontinue the study, whichever occurred first.
Double-Blind Phase Adverse Event	5	6
Double-Blind Phase Death	3	0
Double-Blind Phase Pregnancy	0	1
Double-Blind Phase Lack of Efficacy	1	0
Double-Blind Phase Investigator's Discretion	4	3
Double-Blind Phase Non-Compliance with Study Drug	1	2
Double-Blind Phase Withdrew Consent	41	39
Double-Blind Phase Lost to Follow-up	12	16
Double-Blind Phase Randomized but Never Treated	2	4
Open-Label Extension Phase Lost to Follow-up	0	1

Baseline Characteristics

Study to Evaluate Switching From a Regimen Consisting of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) Fixed Dose Combination (FDC) to Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) FDC in Virologically-Suppressed, HIV-1 Infected Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FTC/RPV/TAF n=438 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=437 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.	Total n=875 Participants Total of all reporting groups
Age, Continuous	48 Years STANDARD_DEVIATION 9.8 • n=5 Participants	47 Years STANDARD_DEVIATION 10.5 • n=7 Participants	48 Years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	373 Participants n=5 Participants	390 Participants n=7 Participants	763 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	47 Participants n=7 Participants	112 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Asian	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Black	118 Participants n=5 Participants	120 Participants n=7 Participants	238 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	291 Participants n=5 Participants	292 Participants n=7 Participants	583 Participants n=5 Participants
Race/Ethnicity, Customized Not Permitted	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	79 Participants n=5 Participants	78 Participants n=7 Participants	157 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	358 Participants n=5 Participants	359 Participants n=7 Participants	717 Participants n=5 Participants
Region of Enrollment Canada	20 Participants n=5 Participants	24 Participants n=7 Participants	44 Participants n=5 Participants
Region of Enrollment Belgium	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	351 Participants n=5 Participants	345 Participants n=7 Participants	696 Participants n=5 Participants
Region of Enrollment United Kingdom	4 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment France	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Switzerland	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Germany	33 Participants n=5 Participants	27 Participants n=7 Participants	60 Participants n=5 Participants
Region of Enrollment Spain	14 Participants n=5 Participants	15 Participants n=7 Participants	29 Participants n=5 Participants
HIV-1 RNA Category < 50 copies/mL	430 Participants n=5 Participants	432 Participants n=7 Participants	862 Participants n=5 Participants
HIV-1 RNA Category ≥ 50 copies/mL	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
CD4 Cell Count	711 cells/µL STANDARD_DEVIATION 292.3 • n=5 Participants	688 cells/µL STANDARD_DEVIATION 263.5 • n=7 Participants	700 cells/µL STANDARD_DEVIATION 278.4 • n=5 Participants
CD4 Cell Count Category ≥ 50 to < 200 cells/µL	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
CD4 Cell Count Category ≥ 200 to < 350 cells/µL	41 Participants n=5 Participants	26 Participants n=7 Participants	67 Participants n=5 Participants
CD4 Cell Count Category ≥ 350 to < 500 cells/µL	63 Participants n=5 Participants	74 Participants n=7 Participants	137 Participants n=5 Participants
CD4 Cell Count Category ≥ 500 cells/ µL	332 Participants n=5 Participants	332 Participants n=7 Participants	664 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: The Full Analysis Set included participants who were randomized and received at least 1 dose of study drug and were on EFV/FTC/TDF prior to the screening visit.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=438 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=437 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm	90.0 percentage of participants	92.0 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Participants in the Full Analysis Set were analyzed.

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=438 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=437 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm	1.1 percentage of participants	0.9 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Full Analysis Set were analyzed.

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=438 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=437 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-defined Snapshot Algorithm	0.7 percentage of participants	0.9 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Full Analysis Set were analyzed.

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

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=438 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=437 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-defined Snapshot	85.2 percentage of participants	85.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Full Analysis Set with on-treatment data were analyzed.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=390 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=403 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Change From Baseline in CD4+ Cell Count at Week 48	23 cells/µL Standard Deviation 156.4	12 cells/µL Standard Deviation 153.3

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Full Analysis Set with on-treatment data were analyzed.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=370 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=371 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Change From Baseline in CD4+ Cell Count at Week 96	12 cells/µL Standard Deviation 199.8	6 cells/µL Standard Deviation 153.2

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Hip DXA Analysis Set (all randomized participants received at least 1 dose of study drug, and had nonmissing baseline hip BMD value) with available data were analyzed.

Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=347 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=367 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	1.279 percentage change Standard Deviation 2.3800	-0.134 percentage change Standard Deviation 2.4930

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Hip DXA Analysis Set with available data were analyzed.

Hip BMD was assessed by DXA scan.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=322 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=345 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Percent Change From Baseline in Hip BMD at Week 96	1.831 percentage change Standard Deviation 3.2925	-0.617 percentage change Standard Deviation 3.3046

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Spine DXA Analysis Set (all randomized participants, received at least 1 dose of study drug, and had nonmissing baseline spine BMD values) with available data were analyzed.

Spine BMD was assessed by DXA scan.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=351 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=369 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Percent Change From Baseline in Spine BMD at Week 48	1.645 percentage change Standard Deviation 3.3198	-0.045 percentage change Standard Deviation 2.9087

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Spine DXA Analysis Set with available data were analyzed.

Spine BMD was assessed by DXA scan.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=327 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=344 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Percent Change From Baseline in Spine BMD at Week 96	1.701 percentage change Standard Deviation 3.6185	0.126 percentage change Standard Deviation 3.2400

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Safety Analysis Set with available data were analyzed.

The HIV Symptoms Index was a 20-item, self-reported measure that addressed presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Twenty HIV symptoms including Fatigue, Fever, Dizziness, Hand/Foot Pain, Memory Loss, Nausea, Diarrhea, Sadness, Nervous/anxious, Sleep Trouble, Skin Problems, Cough, Headache, Appetite Loss, Stomach Pain, Muscle/Joint Pain, Sex Problems, Change in Fat Deposits, Weight Loss, and Hair Loss were assessed. There were 5 possible responses (0 = I don't have this symptom; 1 = It doesn't bother me; 2 = It bothers me a little; 3 = It bothers me; and 4 = It bothers me a lot) for each HIV symptom. Total HIV Symptoms Index Score was derived from all 20 HIV symptoms by counting the number of bothersome symptoms. Total score would be missing if any of the individual items were missing.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=368 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=383 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Change From Baseline in HIV Symptoms Index Score (HIVSI) at Week 48	0 units on a scale Standard Deviation 3.4	-1 units on a scale Standard Deviation 3.4

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Safety Analysis Set with available data were analyzed.

Outcome measures

Outcome measures
Measure	FTC/RPV/TAF n=347 Participants FTC/RPV/TAF (200/25/25 mg) FDC tablet + EFV/FTC/TDF placebo tablet orally once daily for up to 96 weeks.	EFV/FTC/TDF n=347 Participants EFV/FTC/TDF (600/200/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks.
Change From Baseline in HIVSI Score at Week 96	0 units on a scale Standard Deviation 4.1	-1 units on a scale Standard Deviation 3.3

Adverse Events

FTC/RPV/TAF (Double-Blind Phase)

Serious events: 54 serious events

Other events: 277 other events

Deaths: 3 deaths

EFV/FTC/TDF (Double-Blind Phase)

Serious events: 45 serious events

Other events: 270 other events

Deaths: 0 deaths

Open-Label FTC/RPV/TAF From FTC/RPV/TAF

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Open-Label FTC/RPV/TAF From EFV/FTC/TDF

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

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	FTC/RPV/TAF (Double-Blind Phase) n=438 participants at risk Adverse events reported occurred during the Double-Blind Phase in participants from the FTC/RPV/TAF group, who received FTC/RPV/TAF (200/25/25 mg) FDC tablet plus EFV/FTC/TDF placebo tablet administered orally once daily.	EFV/FTC/TDF (Double-Blind Phase) n=437 participants at risk Adverse events reported occurred during the Double-Blind Phase in participants from the EFV/FTC/TDF group, who received EFV/FTC/TDF (600/200/300 mg) FDC tablet plus FTC/RPV/TAF placebo tablet administered orally once daily.	Open-Label FTC/RPV/TAF From FTC/RPV/TAF n=25 participants at risk Adverse events reported occurred during the Open-Label Extension Phase in participants who enrolled into the Open-Label Extension Phase from the FTC/RPV/TAF group and received FTC/RPV/TAF (200/25/25 mg) FDC tablet once daily.	Open-Label FTC/RPV/TAF From EFV/FTC/TDF n=21 participants at risk Adverse events reported occurred during the Open-Label Extension Phase in participants who enrolled into the Open-Label Extension Phase from the EFV/FTC/TDF group and received FTC/RPV/TAF (200/25/25 mg) FDC tablet once daily.
Gastrointestinal disorders Abdominal pain	5.0% 22/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	3.0% 13/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	9.4% 41/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	10.8% 47/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.0% 1/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	9.5% 2/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	5.3% 23/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	3.7% 16/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Infections and infestations Bronchitis	5.5% 24/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	6.4% 28/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	8.0% 2/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	11.6% 51/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	8.9% 39/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	12.0% 3/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.8% 1/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Infections and infestations Pharyngitis	2.7% 12/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.3% 19/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	8.0% 2/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.8% 1/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Infections and infestations Rhinitis	1.1% 5/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	1.6% 7/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	16.0% 4/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Infections and infestations Sinusitis	5.3% 23/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	7.3% 32/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.0% 1/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Infections and infestations Syphilis	8.9% 39/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	7.1% 31/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	9.5% 2/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	16.9% 74/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	16.0% 70/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.0% 1/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.8% 1/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	5.0% 22/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	1.6% 7/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	7.8% 34/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	9.6% 42/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.8% 1/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	8.0% 35/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	8.5% 37/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.0% 1/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	6.4% 28/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	3.4% 15/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Nervous system disorders Headache	8.0% 35/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	7.1% 31/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.0% 1/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Psychiatric disorders Insomnia	5.9% 26/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	5.3% 23/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	10.3% 45/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	6.9% 30/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	8.0% 2/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	9.5% 2/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Eczema	0.91% 4/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.46% 2/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	9.5% 2/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	5.5% 24/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	3.7% 16/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Vascular disorders Hypertension	5.7% 25/438 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	3.7% 16/437 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	4.0% 1/25 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.	0.00% 0/21 • First dose date to last dose date (maximum duration: 172.4 weeks) plus 30 days The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.