Trial Outcomes & Findings for Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF (NCT NCT02121795)

Last Updated: 2020-03-12

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 participant's virologic response 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

668 participants

Primary outcome timeframe

Week 48

Results posted on

2020-03-12

Participant Flow

Participants were enrolled at study sites in North America and Europe. The first participant was screened on 06 May 2014. The last study visit occurred on 1 March 2019.

780 participants were screened.

Participant milestones

Participant milestones
Measure	F/TAF + 3rd Agent Double-Blind Phase: emtricitabine/tenofovir alafenamide (F/TAF) (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks. Open-Label Phase: After Week 96, participants continued to take their blinded study drug and attended visits every 12 weeks until treatment assignments were unblinded, at which point all participants returned for an unblinding visit and were given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program.	FTC/TDF + 3rd Agent Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks. Open-Label Phase: After Week 96, participants continued to take their blinded study drug and attended visits every 12 weeks until treatment assignments were unblinded, at which point all participants returned for an unblinding visit and were given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program.
Double-Blind Phase STARTED	334	334
Double-Blind Phase Safety Analysis Set	333	330
Double-Blind Phase COMPLETED	296	300
Double-Blind Phase NOT COMPLETED	38	34
Open-Label Phase STARTED	33	31
Open-Label Phase COMPLETED	21	21
Open-Label Phase NOT COMPLETED	12	10

Reasons for withdrawal

Reasons for withdrawal
Measure	F/TAF + 3rd Agent Double-Blind Phase: emtricitabine/tenofovir alafenamide (F/TAF) (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks. Open-Label Phase: After Week 96, participants continued to take their blinded study drug and attended visits every 12 weeks until treatment assignments were unblinded, at which point all participants returned for an unblinding visit and were given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program.	FTC/TDF + 3rd Agent Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks. Open-Label Phase: After Week 96, participants continued to take their blinded study drug and attended visits every 12 weeks until treatment assignments were unblinded, at which point all participants returned for an unblinding visit and were given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program.
Double-Blind Phase Randomized but Never Treated	1	4
Double-Blind Phase Withdrawal by Subject	19	16
Double-Blind Phase Lost to Follow-up	7	4
Double-Blind Phase Physician Decision	2	5
Double-Blind Phase Adverse Event	5	0
Double-Blind Phase Non-Compliance with Study Drug	3	1
Double-Blind Phase Protocol Violation	0	3
Double-Blind Phase Death	1	1
Open-Label Phase Physician Decision	8	8
Open-Label Phase Withdrawal by Subject	3	2
Open-Label Phase Lost to Follow-up	1	0

Baseline Characteristics

Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	F/TAF + 3rd Agent n=333 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=330 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.	Total n=663 Participants Total of all reporting groups
Age, Continuous	47 Years STANDARD_DEVIATION 9.9 • n=5 Participants	48 Years STANDARD_DEVIATION 9.7 • n=7 Participants	48 Years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	54 Participants n=7 Participants	102 Participants n=5 Participants
Sex: Female, Male Male	285 Participants n=5 Participants	276 Participants n=7 Participants	561 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	48 Participants n=5 Participants	78 Participants n=7 Participants	126 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	285 Participants n=5 Participants	252 Participants n=7 Participants	537 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Asian	6 participants n=5 Participants	0 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Black	69 participants n=5 Participants	67 participants n=7 Participants	136 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized White	244 participants n=5 Participants	253 participants n=7 Participants	497 participants n=5 Participants
Race/Ethnicity, Customized Not Permitted	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Other	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Canada	5 participants n=5 Participants	9 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Belgium	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment United States	282 participants n=5 Participants	274 participants n=7 Participants	556 participants n=5 Participants
Region of Enrollment Italy	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment United Kingdom	23 participants n=5 Participants	17 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment France	18 participants n=5 Participants	21 participants n=7 Participants	39 participants n=5 Participants
Baseline Third Agent Atazanavir boosted with ritonavir (ATV/r)	53 participants n=5 Participants	50 participants n=7 Participants	103 participants n=5 Participants
Baseline Third Agent Darunavir boosted with ritonavir (DRV/r)	84 participants n=5 Participants	82 participants n=7 Participants	166 participants n=5 Participants
Baseline Third Agent Lopinavir boosted with ritonavir (LPV/r)	18 participants n=5 Participants	18 participants n=7 Participants	36 participants n=5 Participants
Baseline Third Agent Dolutegravir (DTG)	26 participants n=5 Participants	23 participants n=7 Participants	49 participants n=5 Participants
Baseline Third Agent Efavirenz (EFV)	8 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants
Baseline Third Agent Maraviroc (MVC)	1 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants
Baseline Third Agent Nevirapine (NVP)	74 participants n=5 Participants	66 participants n=7 Participants	140 participants n=5 Participants
Baseline Third Agent Raltegravir (RAL)	66 participants n=5 Participants	73 participants n=7 Participants	139 participants n=5 Participants
Baseline Third Agent Rilpivirine (RPV)	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
HIV-1 RNA Categories < 50 copies/mL	329 participants n=5 Participants	326 participants n=7 Participants	655 participants n=5 Participants
HIV-1 RNA Categories >= 50 copies/mL	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
CD4 Cell Count	691 cells/µL STANDARD_DEVIATION 272.6 • n=5 Participants	667 cells/µL STANDARD_DEVIATION 272.3 • n=7 Participants	679 cells/µL STANDARD_DEVIATION 272.5 • n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: The Full Analysis Set included all participants who were randomized into the study and received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	F/TAF + 3rd Agent n=333 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=330 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis	94.3 percentage of participants	93.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 48

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

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

Outcome measures

Outcome measures
Measure	F/TAF + 3rd Agent n=304 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=305 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Percentage Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	1.236 percentage change Standard Deviation 2.6602	-0.071 percentage change Standard Deviation 2.3316

SECONDARY outcome

Timeframe: Baseline; Week 48

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

Spine BMD was assessed by DXA scan.

Outcome measures

Outcome measures
Measure	F/TAF + 3rd Agent n=304 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=309 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Percentage Change From Baseline in Spine BMD at Week 48	1.662 percentage change Standard Deviation 3.1279	-0.109 percentage change Standard Deviation 3.3476

SECONDARY outcome

Timeframe: Week 48

Population: Participants in the Full Analysis Set were analyzed.

The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response 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	F/TAF + 3rd Agent n=333 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=330 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis	91.6 percentage of participants	90.9 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	F/TAF + 3rd Agent n=313 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=311 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Change From Baseline in CD4+ Cell Count at Week 48	20 cells/μL Standard Deviation 161.8	21 cells/μL Standard Deviation 152.7

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Full Analysis Set were analyzed.

The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response 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	F/TAF + 3rd Agent n=333 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=330 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the FDA Snapshot Analysis	83.5 percentage of participants	86.1 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Full Analysis Set were analyzed.

The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response 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	F/TAF + 3rd Agent n=333 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=330 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 as Defined by the FDA Snapshot Analysis	88.6 percentage of participants	89.1 percentage of participants

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	F/TAF + 3rd Agent n=291 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=292 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Percentage Change From Baseline in Hip BMD at Week 96	1.856 percentage change Standard Deviation 3.2195	-0.289 percentage change Standard Deviation 2.9912

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	F/TAF + 3rd Agent n=290 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=296 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Percentage Change From Baseline in Spine BMD at Week 96	2.159 percentage change Standard Deviation 3.8374	-0.109 percentage change Standard Deviation 3.6738

SECONDARY outcome

Timeframe: Baseline; Week 96

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

Outcome measures

Outcome measures
Measure	F/TAF + 3rd Agent n=299 Participants Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg) tablet + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent n=296 Participants Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.
Change From Baseline in CD4+ Cell Count at Week 96	50 cells/μL Standard Deviation 198.7	46 cells/μL Standard Deviation 169.4

Adverse Events

F/TAF + 3rd Agent (Double-Blind)

Serious events: 29 serious events

Other events: 242 other events

Deaths: 2 deaths

FTC/TDF + 3rd Agent (Double-Blind)

Serious events: 31 serious events

Other events: 226 other events

Deaths: 1 deaths

Open-Label F/TAF From F/TAF

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Open-Label F/TAF From FTC/TDF

Serious events: 3 serious events

Other events: 13 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

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	F/TAF + 3rd Agent (Double-Blind) n=333 participants at risk Double-Blind Phase: F/TAF (200/25 mg or 200/10 mg tablet) + FTC/TDF placebo tablet + third agent administered orally once daily for at least 96 weeks.	FTC/TDF + 3rd Agent (Double-Blind) n=330 participants at risk Double-Blind Phase: FTC/TDF 200/300 mg tablet + F/TAF placebo tablet + third agent administered orally once daily for at least 96 weeks.	Open-Label F/TAF From F/TAF n=33 participants at risk Open-Label Phase: F/TAF (200/25 mg or 200/10 mg) tablet orally once daily until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program in participants from the F/TAF + 3rd Agent group.	Open-Label F/TAF From FTC/TDF n=31 participants at risk Open-Label Phase: F/TAF (200/25 mg or 200/10 mg) tablet orally once daily until F/TAF was commercially available or until Gilead Sciences terminated the F/TAF clinical development program in participants from the FTC/TDF + 3rd Agent group.
Gastrointestinal disorders Diarrhoea	13.2% 44/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	12.7% 42/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.0% 1/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	6.9% 23/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.8% 19/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
General disorders Fatigue	7.8% 26/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	7.0% 23/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
General disorders Influenza like illness	1.8% 6/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.0% 10/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.5% 2/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
General disorders Pyrexia	1.8% 6/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	5.2% 17/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Bronchitis	9.6% 32/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	7.9% 26/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.0% 1/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.2% 1/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Fungal skin infection	0.30% 1/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.61% 2/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.5% 2/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Gastroenteritis	3.3% 11/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	2.4% 8/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.1% 2/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Influenza	6.9% 23/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	4.5% 15/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.5% 2/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	12.9% 43/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	8.2% 27/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	12.1% 4/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.5% 2/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Onychomycosis	1.8% 6/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.91% 3/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	9.7% 3/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Sinusitis	6.9% 23/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	8.5% 28/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.1% 2/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	9.7% 3/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Syphilis	5.4% 18/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	2.1% 7/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	9.1% 3/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.5% 2/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	16.2% 54/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	20.3% 67/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.0% 1/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	10.5% 35/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	7.0% 23/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.5% 2/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	11.1% 37/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	8.5% 28/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	9.1% 3/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.5% 2/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	7.8% 26/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.7% 22/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	9.9% 33/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.7% 22/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.2% 1/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	4.5% 15/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.1% 20/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.1% 2/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.2% 1/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	4.5% 15/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.9% 13/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.5% 2/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	11.1% 37/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.1% 20/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.1% 2/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.5% 2/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	5.7% 19/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.3% 11/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	3.0% 1/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Vascular disorders Hypertension	4.8% 16/333 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	6.1% 20/330 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/33 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.	0.00% 0/31 • First dose of study drug to the last dose (maximum: 227.4 weeks) plus 30 days The Safety Analysis Set included all randomized participants who received at least one dose of study drug.