Trial Outcomes & Findings for Open-label Safety Study of E/C/F/TAF (Genvoya®) in HIV-1 Positive Patients With Mild to Moderate Renal Impairment (NCT NCT01818596)

NCT ID: NCT01818596

Last Updated: 2020-03-02

Results Overview

eGFR is a measurement of the kidney's ability to filter blood.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

252 participants

Primary outcome timeframe

Baseline; Week 24

Results posted on

2020-03-02

Participant Flow

Participants were enrolled at study sites in North America, Australia, Asia, and Europe. The first participant was screened on 27 March 2013. The last study visit occurred on 18 July 2018.

380 participants were screened.

Participant milestones

Participant milestones
Measure	Cohort 1 (Treatment-experienced) Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) fixed-dose combination (FDC) tablet administered orally once daily with food for up to 240 weeks in antiretroviral treatment (ART)-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Study STARTED	246	6
Overall Study COMPLETED	215	6
Overall Study NOT COMPLETED	31	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 (Treatment-experienced) Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) fixed-dose combination (FDC) tablet administered orally once daily with food for up to 240 weeks in antiretroviral treatment (ART)-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Study Enrolled but Not Treated	4	0
Overall Study Adverse Event	7	0
Overall Study Death	3	0
Overall Study Investigator's Discretion	4	0
Overall Study Protocol Violation	1	0
Overall Study Withdrew Consent	5	0
Overall Study Lost to Follow-up	7	0

Baseline Characteristics

Open-label Safety Study of E/C/F/TAF (Genvoya®) in HIV-1 Positive Patients With Mild to Moderate Renal Impairment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 (Treatment-experienced) n=242 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants	Total n=248 Participants Total of all reporting groups
Age, Continuous	58 years STANDARD_DEVIATION 9.9 • n=5 Participants	55 years STANDARD_DEVIATION 7.1 • n=7 Participants	58 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	0 Participants n=7 Participants	50 Participants n=5 Participants
Sex: Female, Male Male	192 Participants n=5 Participants	6 Participants n=7 Participants	198 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	34 Participants n=5 Participants	1 Participants n=7 Participants	35 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	44 Participants n=5 Participants	3 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	152 Participants n=5 Participants	2 Participants n=7 Participants	154 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	7 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Race · Not Permitted	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	31 Participants n=5 Participants	1 Participants n=7 Participants	32 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	209 Participants n=5 Participants	5 Participants n=7 Participants	214 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Permitted	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	166 Participants n=5 Participants	5 Participants n=7 Participants	171 Participants n=5 Participants
Region of Enrollment United Kingdom	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Thailand	30 Participants n=5 Participants	1 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment Spain	13 Participants n=5 Participants	0 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Netherlands	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Dominican Republic	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Mexico	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Australia	12 Participants n=5 Participants	0 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment France	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline; Week 24

Population: Participants in the Safety Analysis Set (enrolled and received at least 1 dose of study drug) with available data at the respective time point were analyzed.

eGFR is a measurement of the kidney's ability to filter blood.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=242 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24 Baseline	55.6 mL/min Interval 45.7 to 62.4	60.2 mL/min Interval 45.0 to 63.2
Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24 Change at Week 24	-0.4 mL/min Interval -4.7 to 4.5	-0.3 mL/min Interval -3.6 to 1.3

PRIMARY outcome

Timeframe: Baseline; Week 24

Population: Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

eGFR is a measurement of the kidney's ability to filter blood. The eGFR\_CKD-EPI,cysC method is adjusted for age and sex.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=242 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Change From Baseline in eGFR Calculated by the Chronic Kidney Disease Epidemiology Collaboration Method Based on Cystatin C (eGFR_CKD-EPI,cysC) at Week 24 Baseline	69.7 mL/min/1.73 m^2 Interval 55.9 to 82.7	70.2 mL/min/1.73 m^2 Interval 64.0 to 100.8
Change From Baseline in eGFR Calculated by the Chronic Kidney Disease Epidemiology Collaboration Method Based on Cystatin C (eGFR_CKD-EPI,cysC) at Week 24 Change at Week 24	3.8 mL/min/1.73 m^2 Interval -4.8 to 11.2	3.9 mL/min/1.73 m^2 Interval -3.3 to 13.2

PRIMARY outcome

Timeframe: Baseline; Week 24

Population: Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

eGFR is a measurement of the kidney's ability to filter blood. The eGFR\_CKD-EPI,creatinine method is adjusted for age, race, and sex.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=242 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24 Baseline	54.1 mL/min/1.73 m^2 Interval 46.0 to 62.8	54.4 mL/min/1.73 m^2 Interval 41.7 to 81.4
Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24 Change at Week 24	-1.8 mL/min/1.73 m^2 Interval -6.1 to 4.9	-2.6 mL/min/1.73 m^2 Interval -11.1 to -0.9

SECONDARY outcome

Timeframe: Baseline; Week 2, 4, or 8; Week 24

Population: Participants in the Pharmacodynamic (PD) Substudy Analysis Set (enrolled in the pharmacokinetic (PK)/PD substudy, received at least 1 dose of study drug, and had baseline and at least 1 postbaseline assessment for aGFR assessed by CLiohexol) with available data at the respective time point were analyzed.

aGFR was directly measured using iohexol plasma clearance (CLiohexol).

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=32 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy Baseline	60.1 mL/min Standard Deviation 19.06	—
Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy Change at Week 2, 4, or 8	-0.6 mL/min Standard Deviation 8.45	—
Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy Change at Week 24	1.4 mL/min Standard Deviation 9.91	—

SECONDARY outcome

Timeframe: Baseline; Weeks 24 and 48

Population: Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

CTX is a biomarker of bone turnover.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=226 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48 Change at Week 24	-3.9 percentage change Interval -15.8 to 10.7	16.9 percentage change Interval 0.0 to 21.7
Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48 Change at Week 48	-2.2 percentage change Interval -16.7 to 24.4	0.0 percentage change Interval -4.8 to 10.8

SECONDARY outcome

Timeframe: Baseline; Weeks 24 and 48

Population: Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

P1NP is a biomarker of bone turnover.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=229 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48 Change at Week 24	-12.98 percentage change Interval -34.48 to 8.86	6.44 percentage change Interval -5.08 to 47.62
Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48 Change at Week 48	-25.29 percentage change Interval -45.98 to 2.0	2.27 percentage change Interval -29.12 to 41.8

SECONDARY outcome

Timeframe: Baseline; Weeks 24, 48, 96, and 144

Population: Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Urine RBP is a renal biomarker which is used to evaluate drug-induced kidney injury.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=227 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 Change at Week 24	-56.2 percentage change Interval -90.0 to -11.8	68.8 percentage change Interval -37.1 to 72.6
Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 Change at Week 48	-68.9 percentage change Interval -92.2 to -20.5	47.8 percentage change Interval 13.3 to 78.9
Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 Change at Week 96	-64.1 percentage change Interval -91.4 to 9.8	55.0 percentage change Interval -10.5 to 197.0
Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 Change at Week 144	-63.8 percentage change Interval -92.4 to 4.6	-1.0 percentage change Interval -10.2 to 43.4

SECONDARY outcome

Timeframe: Baseline; Weeks 24, 48, 96, and 144

Population: Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Urine beta-2-microglobulin is a renal biomarker which is used to evaluate drug-induced kidney injury.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=224 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 Change at Week 96	-83.6 percentage change Interval -96.4 to -31.1	-45.9 percentage change Interval -95.8 to 195.6
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 Change at Week 24	-70.7 percentage change Interval -92.6 to -11.1	-19.5 percentage change Interval -93.0 to 81.3
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 Change at Week 48	-76.5 percentage change Interval -94.6 to -17.7	-59.2 percentage change Interval -85.0 to 34.3
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 Change at Week 144	-81.9 percentage change Interval -95.5 to -18.0	-3.6 percentage change Interval -66.7 to 73.5

SECONDARY outcome

Timeframe: Baseline up to Week 240 plus 30 days

Population: Participants in the Safety Analysis Set were analyzed.

Adverse events (AEs) and graded laboratory abnormalities occurring during the E/C/F/TAF treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=242 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities Any AE	95.5 percentage of participants	100.0 percentage of participants
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities Grade 3 or 4 AE	22.3 percentage of participants	16.7 percentage of participants
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities AE leading to drug discontinuation	5.0 percentage of participants	0 percentage of participants
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities Serious AE	22.7 percentage of participants	16.7 percentage of participants
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities Grade 3 or 4 laboratory abnormality	42.6 percentage of participants	66.7 percentage of participants

SECONDARY outcome

Timeframe: Weeks 24, 48, 96, and 144

Population: Full Analysis Set included participants who were enrolled and received at least 1 dose of study drug.

The percentage of participants achieving HIV-1 RNA \< 50 Copies/mL at Weeks 24, 48, 96, and 144 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	Cohort 1 (Treatment-experienced) n=242 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 Week 24	95.0 percentage of participants	83.3 percentage of participants
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 Week 48	93.0 percentage of participants	100.0 percentage of participants
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 Week 96	88.4 percentage of participants	100.0 percentage of participants
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 Week 144	81.4 percentage of participants	100.0 percentage of participants

SECONDARY outcome

Timeframe: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Population: Participants in the PK Substudy Analysis Set (enrolled in the PK/PD substudy, received at least 1 dose of study drug, and for whom steady-state PK parameters were available) with available data were analyzed.

Cmax is defined as the maximum concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=30 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Pharmacokinetic (PK) Parameter: Cmax of TAF	269.8 ng/mL Standard Deviation 180.77	—

SECONDARY outcome

Timeframe: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

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

Tmax is defined as the time of Cmax. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=30 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
PK Parameter: Tmax of TAF	0.97 hours Interval 0.5 to 1.98	—

SECONDARY outcome

Timeframe: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

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

Clast is defined as the last observable concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=30 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
PK Parameter: Clast of TAF	7.6 ng/mL Standard Deviation 25.73	—

SECONDARY outcome

Timeframe: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

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

Tlast is defined as the time of Clast. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=30 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
PK Parameter: Tlast of TAF	4.45 hours Interval 3.82 to 5.0	—

SECONDARY outcome

Timeframe: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

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

λz is defined as the terminal elimination rate constant. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=30 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
PK Parameter: λz of TAF	1.764 1/hour Standard Deviation 1.4521	—

SECONDARY outcome

Timeframe: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

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

AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=30 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
PK Parameter: AUCtau of TAF	368.4 ng*h/mL Standard Deviation 631.20	—

SECONDARY outcome

Timeframe: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

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

t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=30 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
PK Parameter: t1/2 of TAF	0.43 hours Interval 0.37 to 0.52	—

SECONDARY outcome

Timeframe: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Population: Participants who were enrolled in the PK/PD substudy, received at least 1 dose of study drug, and for whom the steady-state PK parameter (AUCtau) of TFV-DP was evaluable were analyzed.

TFV-DP is an active phosphorylated metabolite of tenofovir alafenamide. AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=23 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study	50.6 µmol*h/L Standard Deviation 55.75	—

SECONDARY outcome

Timeframe: Baseline; Weeks 48, 96, and 144

Population: Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

eGFR is a measurement of the kidney's ability to filter blood.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=242 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144 Baseline	55.6 mL/min Interval 45.7 to 62.4	60.2 mL/min Interval 45.0 to 63.2
Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144 Change at Week 48	-0.6 mL/min Interval -5.4 to 5.4	-0.6 mL/min Interval -1.9 to 4.2
Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144 Change at Week 96	0.6 mL/min Interval -4.6 to 7.2	-1.9 mL/min Interval -4.0 to 6.0
Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144 Change at Week 144	1.5 mL/min Interval -4.8 to 7.2	7.0 mL/min Interval 3.3 to 11.2

SECONDARY outcome

Timeframe: Baseline; Weeks 48, 96, and 144

Population: Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

eGFR is a measurement of the kidney's ability to filter blood. The eGFR\_CKD-EPI,cysC method is adjusted for age and sex.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=242 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144 Baseline	69.7 mL/min/1.73 m^2 Interval 55.9 to 82.7	70.2 mL/min/1.73 m^2 Interval 64.0 to 100.8
Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144 Change at Week 48	1.7 mL/min/1.73 m^2 Interval -7.3 to 12.0	7.3 mL/min/1.73 m^2 Interval -0.1 to 12.2
Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144 Change at Week 96	3.2 mL/min/1.73 m^2 Interval -3.6 to 11.8	5.6 mL/min/1.73 m^2 Interval -7.2 to 20.8
Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144 Change at Week 144	3.1 mL/min/1.73 m^2 Interval -4.8 to 11.8	3.5 mL/min/1.73 m^2 Interval -1.8 to 22.9

SECONDARY outcome

Timeframe: Baseline; Weeks 48, 96, and 144

Population: Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

eGFR is a measurement of the kidney's ability to filter blood. The eGFR\_CKD-EPI,creatinine method is adjusted for age, race, and sex.

Outcome measures

Outcome measures
Measure	Cohort 1 (Treatment-experienced) n=242 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 Participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144 Change at Week 96	0.1 mL/min/1.73 m^2 Interval -5.7 to 6.4	-3.1 mL/min/1.73 m^2 Interval -9.5 to 2.1
Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144 Change at Week 144	1.7 mL/min/1.73 m^2 Interval -5.3 to 8.5	0.9 mL/min/1.73 m^2 Interval -5.7 to 6.0
Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144 Baseline	54.1 mL/min/1.73 m^2 Interval 46.0 to 62.8	54.4 mL/min/1.73 m^2 Interval 41.7 to 81.4
Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144 Change at Week 48	-1.7 mL/min/1.73 m^2 Interval -7.9 to 4.2	-3.0 mL/min/1.73 m^2 Interval -4.9 to 0.6

Adverse Events

Cohort 1 (Treatment-experienced)

Serious events: 55 serious events

Other events: 195 other events

Deaths: 0 deaths

Cohort 2 (Treatment-naive)

Serious events: 1 serious events

Other events: 5 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	Cohort 1 (Treatment-experienced) n=242 participants at risk E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	Cohort 2 (Treatment-naive) n=6 participants at risk E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Cardiac disorders Supraventricular extrasystoles	0.41% 1/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	6.6% 16/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	13.2% 32/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Gastrointestinal disorders Gingival pain	0.00% 0/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Gastrointestinal disorders Mouth ulceration	0.83% 2/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	9.1% 22/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	5.4% 13/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
General disorders Chest pain	4.1% 10/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
General disorders Fatigue	8.3% 20/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
General disorders Peripheral swelling	3.3% 8/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Infections and infestations Bronchitis	15.3% 37/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Infections and infestations Hordeolum	0.41% 1/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Infections and infestations Influenza	4.1% 10/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	10.3% 25/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Infections and infestations Sinusitis	7.4% 18/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	16.1% 39/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	10.3% 25/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Injury, poisoning and procedural complications Exposure to communicable disease	0.41% 1/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Investigations Cardiac murmur	0.41% 1/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Investigations Electrocardiogram st-t change	0.00% 0/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Metabolism and nutrition disorders Dyslipidaemia	2.1% 5/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperlipidaemia	2.9% 7/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	33.3% 2/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	1.2% 3/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Metabolism and nutrition disorders Vitamin d deficiency	1.7% 4/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	14.0% 34/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthritis	1.2% 3/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	11.2% 27/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteopenia	10.7% 26/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteoporosis	5.4% 13/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	10.3% 25/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	33.3% 2/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Tendonitis	2.1% 5/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anogenital warts	0.41% 1/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Nervous system disorders Dizziness	7.4% 18/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Nervous system disorders Headache	8.3% 20/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Nervous system disorders Migraine	0.83% 2/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Nervous system disorders Paraesthesia	5.4% 13/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Nervous system disorders Somnolence	1.2% 3/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Renal and urinary disorders Proteinuria	1.2% 3/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Renal and urinary disorders Renal cyst	5.8% 14/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Reproductive system and breast disorders Erectile dysfunction	2.5% 6/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	9.9% 24/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis	1.7% 4/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	1.7% 4/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	6.2% 15/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash generalised	0.41% 1/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Vascular disorders Hypertension	9.9% 24/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	0.00% 0/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
Vascular disorders Orthostatic hypotension	0.41% 1/242 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.	16.7% 1/6 • First dose date up to Week 240 plus 30 days Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.