Trial Outcomes & Findings for A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B (NCT NCT00116805)

NCT ID: NCT00116805

Last Updated: 2017-03-09

Results Overview

Complete response was a composite endpoint defined as histological response and HBV DNA \< 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4. A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 266 participants
• Primary outcome timeframe: Baseline; Week 48
• Results posted on: 2017-03-09

Participant Flow

Participants were enrolled at study sites in North America, Europe, and Australia/New Zealand. The first participant was screened on 09 June 2005. The last study visit occurred on 28 January 2016.

603 participants were screened.

Participant milestones

Measure	TDF-TDF Tenofovir disoproxil fumarate (TDF) 300 mg plus placebo to match adefovir dipivoxil (ADV) (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Double-blind Period Through Week 48 STARTED	176	90
Double-blind Period Through Week 48 COMPLETED	165	85
Double-blind Period Through Week 48 NOT COMPLETED	11	5
Open-label Period Weeks 49 - 96 STARTED	154	84
Open-label Period Weeks 49 - 96 COMPLETED	144	83
Open-label Period Weeks 49 - 96 NOT COMPLETED	10	1
Open-label Period Weeks 97 - 144 STARTED	144	83
Open-label Period Weeks 97 - 144 COMPLETED	133	74
Open-label Period Weeks 97 - 144 NOT COMPLETED	11	9
Open-label Period Weeks 145 - 192 STARTED	133	74
Open-label Period Weeks 145 - 192 COMPLETED	123	68
Open-label Period Weeks 145 - 192 NOT COMPLETED	10	6
Open-label Period Weeks 193 - 240 STARTED	123	68
Open-label Period Weeks 193 - 240 COMPLETED	110	64
Open-label Period Weeks 193 - 240 NOT COMPLETED	13	4
Open-label Period Weeks 241 - 288 STARTED	110	64
Open-label Period Weeks 241 - 288 COMPLETED	104	64
Open-label Period Weeks 241 - 288 NOT COMPLETED	6	0
Open-label Period Weeks 289 - 336 STARTED	104	64
Open-label Period Weeks 289 - 336 COMPLETED	98	57
Open-label Period Weeks 289 - 336 NOT COMPLETED	6	7
Open-label Period Weeks 337 - 384 STARTED	98	57
Open-label Period Weeks 337 - 384 COMPLETED	90	56
Open-label Period Weeks 337 - 384 NOT COMPLETED	8	1
Open-label Period Weeks 385 - 432 STARTED	59	30
Open-label Period Weeks 385 - 432 COMPLETED	57	30
Open-label Period Weeks 385 - 432 NOT COMPLETED	2	0
Open-label Period Weeks 433 - 480 STARTED	57	29
Open-label Period Weeks 433 - 480 COMPLETED	53	29
Open-label Period Weeks 433 - 480 NOT COMPLETED	4	0

Reasons for withdrawal

Measure	TDF-TDF Tenofovir disoproxil fumarate (TDF) 300 mg plus placebo to match adefovir dipivoxil (ADV) (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Double-blind Period Through Week 48 Lost to Follow-up	6	2
Double-blind Period Through Week 48 Protocol Violation	1	1
Double-blind Period Through Week 48 Withdrew Consent	4	2
Open-label Period Weeks 49 - 96 Investigator's Discretion	1	0
Open-label Period Weeks 49 - 96 Lost to Follow-up	2	0
Open-label Period Weeks 49 - 96 Protocol Violation	2	0
Open-label Period Weeks 49 - 96 Safety, Tolerability, or Efficacy Reason	1	0
Open-label Period Weeks 49 - 96 Seroconversion	2	0
Open-label Period Weeks 49 - 96 Withdrew Consent	2	1
Open-label Period Weeks 97 - 144 Completed Study	1	0
Open-label Period Weeks 97 - 144 Investigator's Discretion	2	0
Open-label Period Weeks 97 - 144 Lost to Follow-up	5	2
Open-label Period Weeks 97 - 144 Protocol Violation	0	1
Open-label Period Weeks 97 - 144 Seroconversion	2	3
Open-label Period Weeks 97 - 144 Withdrew Consent	1	3
Open-label Period Weeks 145 - 192 Completed Study	1	1
Open-label Period Weeks 145 - 192 Investigator's Discretion	2	0
Open-label Period Weeks 145 - 192 Lost to Follow-up	3	1
Open-label Period Weeks 145 - 192 Protocol Violation	1	0
Open-label Period Weeks 145 - 192 Safety, Tolerability, or Efficacy Reason	0	1
Open-label Period Weeks 145 - 192 Seroconversion	0	1
Open-label Period Weeks 145 - 192 Withdrew Consent	3	2
Open-label Period Weeks 193 - 240 Completed Study	0	1
Open-label Period Weeks 193 - 240 Investigator's Discretion	1	0
Open-label Period Weeks 193 - 240 Lost to Follow-up	3	0
Open-label Period Weeks 193 - 240 Safety, Tolerability, or Efficacy Reason	2	2
Open-label Period Weeks 193 - 240 Withdrew Consent	7	1
Open-label Period Weeks 241 - 288 Safety, Tolerability, or Efficacy Reason	2	0
Open-label Period Weeks 241 - 288 Withdrew Consent	4	0
Open-label Period Weeks 289 - 336 Completed Study	0	1
Open-label Period Weeks 289 - 336 Investigator's Discretion	3	2
Open-label Period Weeks 289 - 336 Lost to Follow-up	1	1
Open-label Period Weeks 289 - 336 Protocol Violation	0	1
Open-label Period Weeks 289 - 336 Safety, Tolerability, or Efficacy Reason	0	1
Open-label Period Weeks 289 - 336 Study Site Discontinued	0	1
Open-label Period Weeks 289 - 336 Withdrew Consent	2	0
Open-label Period Weeks 337 - 384 Completed Study	1	0
Open-label Period Weeks 337 - 384 Investigator's Discretion	1	0
Open-label Period Weeks 337 - 384 Lost to Follow-up	2	0
Open-label Period Weeks 337 - 384 Protocol Violation	1	0
Open-label Period Weeks 337 - 384 Withdrew Consent	3	1
Open-label Period Weeks 385 - 432 Investigator's Discretion	1	0
Open-label Period Weeks 385 - 432 Withdrew Consent	1	0
Open-label Period Weeks 433 - 480 Investigator's Discretion	1	0
Open-label Period Weeks 433 - 480 Withdrew Consent	3	0

Baseline Characteristics

A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B

Baseline characteristics by cohort

Measure	TDF-TDF n=176 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=90 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	Total n=266 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	173 Participants n=5 Participants	89 Participants n=7 Participants	262 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	34 years STANDARD_DEVIATION 11.3 • n=5 Participants	34 years STANDARD_DEVIATION 12.2 • n=7 Participants	34 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	26 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	119 Participants n=5 Participants	64 Participants n=7 Participants	183 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	14 participants n=7 Participants	44 participants n=5 Participants
Region of Enrollment Greece	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Spain	7 participants n=5 Participants	2 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Turkey	10 participants n=5 Participants	4 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Italy	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United Kingdom	6 participants n=5 Participants	1 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment France	11 participants n=5 Participants	3 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Czech Republic	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Canada	17 participants n=5 Participants	10 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Poland	16 participants n=5 Participants	8 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment Australia	22 participants n=5 Participants	6 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Bulgaria	17 participants n=5 Participants	11 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Germany	20 participants n=5 Participants	8 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Netherlands	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment New Zealand	10 participants n=5 Participants	11 participants n=7 Participants	21 participants n=5 Participants
Baseline Alanine Aminotransferase (ALT) above the Upper Limit of the Normal (ULN) Range Yes	169 participants n=5 Participants	90 participants n=7 Participants	259 participants n=5 Participants
Baseline Alanine Aminotransferase (ALT) above the Upper Limit of the Normal (ULN) Range No	7 participants n=5 Participants	0 participants n=7 Participants	7 participants n=5 Participants
Prior Lamivudine or FTC Treatment Yes	8 participants n=5 Participants	1 participants n=7 Participants	9 participants n=5 Participants
Prior Lamivudine or FTC Treatment No	168 participants n=5 Participants	89 participants n=7 Participants	257 participants n=5 Participants
Baseline Hepatitis B Deoxyribonucleic Acid (HBV DNA)	8.64 log10 copies/mL STANDARD_DEVIATION 1.076 • n=5 Participants	8.88 log10 copies/mL STANDARD_DEVIATION 0.930 • n=7 Participants	8.72 log10 copies/mL STANDARD_DEVIATION 1.033 • n=5 Participants
Baseline Knodell Necroinflammatory Score	8.3 units on a scale STANDARD_DEVIATION 2.11 • n=5 Participants	8.5 units on a scale STANDARD_DEVIATION 2.07 • n=7 Participants	8.4 units on a scale STANDARD_DEVIATION 2.09 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline; Week 48

Population: Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study medication; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Complete response was a composite endpoint defined as histological response and HBV DNA < 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.

A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40.

Outcome measures

Measure	TDF-TDF n=176 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=90 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48	66.5 percentage of participants	12.2 percentage of participants	—	—

SECONDARY outcome

Timeframe: Week 48

Population: Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Outcome measures

Measure	TDF-TDF n=176 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=90 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48	76.1 percentage of participants	13.3 percentage of participants	—	—

SECONDARY outcome

Timeframe: Week 96

Population: Participants in the Randomized and Treated Analysis Set with available data were analyzed. Data included for participants who discontinued study unless the discontinuation was unrelated to protocol criteria.

Outcome measures

Measure	TDF-TDF n=165 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=86 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96	77.6 percentage of participants	77.9 percentage of participants	—	—

SECONDARY outcome

Timeframe: Weeks 144, 192, 240, 288, 336, and 384

Population: Randomized and Treated Analysis Set. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.

Outcome measures

Measure	TDF-TDF n=166 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=88 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 144	71.7 percentage of participants	70.5 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 192	67.9 percentage of participants	71.6 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 240	63.4 percentage of participants	66.3 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 288	61.3 percentage of participants	64.8 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 336	59.4 percentage of participants	62.1 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 384	56.1 percentage of participants	60.5 percentage of participants	—	—

SECONDARY outcome

Timeframe: Weeks 432 and 480

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added emtricitabine to their open-label TDF regimen were included in the analysis.

Outcome measures

Measure	TDF-TDF n=57 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=29 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 Week 432	93.0 percentage of participants	100.0 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 Week 480	98.0 percentage of participants	96.6 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Outcome measures

Measure	TDF-TDF n=160 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=85 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 432	-6.13 log10 IU/mL Standard Deviation 1.306	-6.45 log10 IU/mL Standard Deviation 1.008	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 480	-6.18 log10 IU/mL Standard Deviation 1.300	-6.37 log10 IU/mL Standard Deviation 1.159	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 48	-6.17 log10 IU/mL Standard Deviation 1.067	-3.93 log10 IU/mL Standard Deviation 1.728	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 96	-6.26 log10 IU/mL Standard Deviation 1.137	-6.38 log10 IU/mL Standard Deviation 1.184	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 144	-6.32 log10 IU/mL Standard Deviation 1.098	-6.31 log10 IU/mL Standard Deviation 1.407	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 192	-6.30 log10 IU/mL Standard Deviation 1.203	-6.49 log10 IU/mL Standard Deviation 1.028	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 240	-6.22 log10 IU/mL Standard Deviation 1.217	-6.45 log10 IU/mL Standard Deviation 0.986	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 288	-6.27 log10 IU/mL Standard Deviation 1.248	-6.49 log10 IU/mL Standard Deviation 1.003	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 336	-6.35 log10 IU/mL Standard Deviation 1.208	-6.46 log10 IU/mL Standard Deviation 1.017	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 384	-6.38 log10 IU/mL Standard Deviation 1.167	-6.28 log10 IU/mL Standard Deviation 1.450	—	—

SECONDARY outcome

Timeframe: Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Outcome measures

Measure	TDF-TDF n=144 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=80 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 96	-0.10 log10 IU/mL Standard Deviation 0.422	-2.43 log10 IU/mL Standard Deviation 1.724	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 144	-0.19 log10 IU/mL Standard Deviation 0.475	-2.27 log10 IU/mL Standard Deviation 1.866	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 192	-0.20 log10 IU/mL Standard Deviation 0.565	-2.41 log10 IU/mL Standard Deviation 1.662	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 240	-0.14 log10 IU/mL Standard Deviation 0.706	-2.49 log10 IU/mL Standard Deviation 1.599	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 288	-0.18 log10 IU/mL Standard Deviation 0.762	-2.62 log10 IU/mL Standard Deviation 1.679	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 336	-0.25 log10 IU/mL Standard Deviation 0.618	-2.59 log10 IU/mL Standard Deviation 1.622	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 384	-0.29 log10 IU/mL Standard Deviation 0.643	-2.34 log10 IU/mL Standard Deviation 1.821	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 432	-0.13 log10 IU/mL Standard Deviation 0.854	-2.32 log10 IU/mL Standard Deviation 1.694	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 480	-0.24 log10 IU/mL Standard Deviation 0.630	-2.16 log10 IU/mL Standard Deviation 1.882	—	—

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.

Outcome measures

Measure	TDF-TDF n=176 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=90 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With Histological Response at Week 48 Yes	74.4 percentage of participants	67.8 percentage of participants	—	—
Percentage of Participants With Histological Response at Week 48 No	25.6 percentage of participants	32.2 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 240

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.

Outcome measures

Measure	TDF-TDF n=76 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=48 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With Histological Response at Week 240 Yes	88.2 percentage of participants	89.6 percentage of participants	—	—
Percentage of Participants With Histological Response at Week 240 No	11.8 percentage of participants	10.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set with measurements at Baseline and Week 48 were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis.

The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).

Outcome measures

Measure	TDF-TDF n=157 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=79 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 Knodell Necroinflammatory Score	-3.6 units on a scale Standard Deviation 2.30	-3.2 units on a scale Standard Deviation 2.35	—	—
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 Ishak Necroinflammatory Score	-2.7 units on a scale Standard Deviation 1.70	-2.6 units on a scale Standard Deviation 1.94	—	—

SECONDARY outcome

Timeframe: Baseline; Week 240

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).

Outcome measures

Measure	TDF-TDF n=76 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=48 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 Knodell Necroinflammatory Score	-4.8 units on a scale Standard Deviation 2.34	-5.1 units on a scale Standard Deviation 2.43	—	—
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 Ishak Necroinflammatory Score	-4.1 units on a scale Standard Deviation 2.14	-4.5 units on a scale Standard Deviation 2.32	—	—

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.

Outcome measures

Measure	TDF-TDF n=176 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=90 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Improvement - Necroinflammation	81.3 percentage of participants	78.9 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 No Change - Necroinflammation	4.5 percentage of participants	3.3 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Worsening - Necroinflammation	3.4 percentage of participants	5.6 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Missing Data - Necroinflammation	10.8 percentage of participants	12.2 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Improvement - Fibrosis	19.9 percentage of participants	20.0 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 No Change - Fibrosis	63.6 percentage of participants	61.1 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Worsening - Fibrosis	5.1 percentage of participants	6.7 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Missing Data - Fibrosis	11.4 percentage of participants	12.2 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 240

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.

Outcome measures

Measure	TDF-TDF n=76 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=48 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 No Change - Fibrosis	39.5 percentage of participants	39.6 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 Worsening - Fibrosis	3.9 percentage of participants	2.1 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 Improvement - Necroinflammation	96.1 percentage of participants	97.9 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 No Change - Necroinflammation	3.9 percentage of participants	2.1 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 Worsening - Necroinflammation	0 percentage of participants	0 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 Improvement - Fibrosis	56.6 percentage of participants	58.3 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline were analyzed; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.

ALT normalization was defined as ALT > upper limit of normal (ULN) at baseline and within the normal range at the end of blinded treatment. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.

Outcome measures

Measure	TDF-TDF n=169 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=90 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48	68.0 percentage of participants	54.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.

ALT normalization was defined as ALT > ULN at baseline and within the normal range at Week 96. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.

Outcome measures

Measure	TDF-TDF n=158 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=86 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With ALT Normalization at Week 96	65.2 percentage of participants	74.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Weeks 144, 192, 240, 288, 336, and 384

Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline and available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.

ALT normalization was defined as ALT > ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.

Outcome measures

Measure	TDF-TDF n=161 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=87 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 144	60.2 percentage of participants	67.8 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 192	59.6 percentage of participants	69.4 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 240	50.0 percentage of participants	65.9 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 288	51.3 percentage of participants	70.1 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 336	46.2 percentage of participants	67.9 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 384	52.6 percentage of participants	67.1 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Weeks 432 and 480

Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline and with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

ALT normalization was defined as ALT > ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.

Outcome measures

Measure	TDF-TDF n=54 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=29 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With ALT Normalization at Weeks 432 and 480 Week 432	79.6 percentage of participants	78.6 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 432 and 480 Week 480	75.0 percentage of participants	82.8 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Outcome measures

Measure	TDF-TDF n=160 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=84 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 48	-107.2 U/L Standard Deviation 109.44	-106.1 U/L Standard Deviation 118.90	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 96	-107.8 U/L Standard Deviation 108.07	-120.4 U/L Standard Deviation 138.03	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 144	-100.7 U/L Standard Deviation 105.96	-126.2 U/L Standard Deviation 150.46	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 192	-101.4 U/L Standard Deviation 108.63	-139.6 U/L Standard Deviation 137.95	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 240	-95.9 U/L Standard Deviation 117.03	-134.8 U/L Standard Deviation 135.59	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 288	-102.3 U/L Standard Deviation 111.68	-130.9 U/L Standard Deviation 123.08	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 336	-101.9 U/L Standard Deviation 112.72	-132.3 U/L Standard Deviation 125.81	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 384	-108.1 U/L Standard Deviation 118.05	-133.7 U/L Standard Deviation 128.57	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 432	-105.0 U/L Standard Deviation 139.61	-162.1 U/L Standard Deviation 157.83	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 480	-92.3 U/L Standard Deviation 83.56	-157.5 U/L Standard Deviation 159.96	—	—

SECONDARY outcome

Timeframe: Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480

Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.

Outcome measures

Measure	TDF-TDF n=141 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=81 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 192	-1.3 U/L Standard Deviation 19.57	-7.8 U/L Standard Deviation 27.07	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 240	3.7 U/L Standard Deviation 32.48	-8.1 U/L Standard Deviation 22.92	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 288	-1.6 U/L Standard Deviation 19.91	-10.3 U/L Standard Deviation 25.26	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 336	-1.2 U/L Standard Deviation 19.72	-9.3 U/L Standard Deviation 22.69	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 384	-4.4 U/L Standard Deviation 24.87	-6.9 U/L Standard Deviation 31.76	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 432	-4.3 U/L Standard Deviation 24.27	-11.6 U/L Standard Deviation 27.09	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 480	-5.5 U/L Standard Deviation 19.28	-7.1 U/L Standard Deviation 39.76	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 96	-2.0 U/L Standard Deviation 17.94	-6.9 U/L Standard Deviation 59.64	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 144	-0.4 U/L Standard Deviation 21.94	-0.7 U/L Standard Deviation 82.70	—	—

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set who were HBeAg-positive at baseline and with available data were analyzed.

HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 48. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 48.

Outcome measures

Measure	TDF-TDF n=153 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=80 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48 HBeAg Loss	22.2 percentage of participants	17.5 percentage of participants	—	—
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48 HBeAg Seroconversion	20.9 percentage of participants	17.5 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Randomized and Treated Analysis Set who were HBeAg-positive at baseline and with available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.

HBeAg loss was defined as HBeAg positive at baseline and HBeAg negative at Week 96. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative at baseline to positive at Week 96.

Outcome measures

Measure	TDF-TDF n=158 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=82 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96 HBeAg Loss	25.9 percentage of participants	25.6 percentage of participants	—	—
Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96 Seroconversion to Anti-HBe	22.8 percentage of participants	22.0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set with available data were analyzed.

HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 48. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 48.

Outcome measures

Measure	TDF-TDF n=158 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=82 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48 HBsAg Loss	3.2 percentage of participants	0 percentage of participants	—	—
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48 HBsAg Seroconversion	1.3 percentage of participants	0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Participants in the Randomized and Treated Analysis Set with available data were analyzed. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.

HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.

Outcome measures

Measure	TDF-TDF n=171 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=86 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96 HBsAg Loss	5.3 percentage of participants	5.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96 Anti-HBs Seroconversion	4.1 percentage of participants	4.7 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480

Population: Randomized and Treated Analysis Set. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.

HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.

Outcome measures

Measure	TDF-TDF n=174 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=89 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 144	7.5 percentage of participants	8.0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 144	5.2 percentage of participants	6.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 192	9.4 percentage of participants	7.9 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 192	6.4 percentage of participants	6.7 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 240	9.2 percentage of participants	8.0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 240	6.3 percentage of participants	8.0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 288	9.2 percentage of participants	8.0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 288	6.4 percentage of participants	8.0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 336	10.3 percentage of participants	7.9 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 336	7.5 percentage of participants	7.9 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 384	11.0 percentage of participants	9.0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 384	8.1 percentage of participants	7.9 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 432	10.9 percentage of participants	10.2 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 432	7.6 percentage of participants	8.0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 480	10.9 percentage of participants	10.1 percentage of participants	—	—
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 480	8.0 percentage of participants	7.9 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL, those with viral breakthrough, and those who discontinued after Week 24 with HBV DNA ≥ 400 copies/mL.

Outcome measures

Measure	TDF-TDF n=176 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=90 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) Participants evaluated	31 participants	75 participants	—	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	2 participants	8 participants	—	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	13 participants	17 participants	—	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) No genotypic changes (wild-type virus)	7 participants	43 participants	—	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) Unable to be genotyped	9 participants	7 participants	—	—

SECONDARY outcome

Timeframe: Baseline; Weeks 49 to 96

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 48 (ie, entered the open-label phase) were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 96 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 48 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Outcome measures

Measure	TDF-TDF n=154 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=15 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=84 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC n=13 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) Participants evaluated	18 participants	13 participants	16 participants	10 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	2 participants	0 participants	2 participants	3 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	3 participants	1 participants	1 participants	2 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) No genotypic changes (wild-type virus)	10 participants	5 participants	12 participants	3 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) Unable to be genotyped	3 participants	7 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: Baseline; Weeks 97 to 144

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 96 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 144 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 96 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 96 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Outcome measures

Measure	TDF-TDF n=126 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=17 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=69 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC n=13 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) Participants evaluated	2 participants	7 participants	5 participants	5 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	1 participants	2 participants	2 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	0 participants	3 participants	3 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) No genotypic changes (wild-type virus)	1 participants	2 participants	0 participants	3 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) Unable to be genotyped	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline; Weeks 145 to 192

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 144 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 192 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 144 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 144 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Outcome measures

Measure	TDF-TDF n=115 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=15 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=61 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC n=10 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) Participants evaluated	2 participants	5 participants	1 participants	1 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	0 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	1 participants	0 participants	1 participants	1 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) No genotypic changes (wild-type virus)	0 participants	1 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) Unable to be genotyped	1 participants	3 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline; Weeks 193 to 240

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 192 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 240 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 192 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 192 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Outcome measures

Measure	TDF-TDF n=103 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=13 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=55 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC n=12 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) Participants evaluated	3 participants	3 participants	0 participants	1 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	0 participants	0 participants	0 participants	1 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	2 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) No genotypic changes (wild-type virus)	1 participants	2 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) Unable to be genotyped	0 participants	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline; Weeks 241 to 288

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 240 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 288 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 240 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 240 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Outcome measures

Measure	TDF-TDF n=92 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=11 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=52 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC n=12 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) Participants evaluated	3 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	0 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	0 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) No genotypic changes (wild-type virus)	2 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) Unable to be genotyped	1 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline; Weeks 289 to 336

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 288 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 336 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 288 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 288 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Outcome measures

Measure	TDF-TDF n=93 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=12 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=53 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC n=12 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) Participants evaluated	1 participants	0 participants	1 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	0 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	0 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) No genotypic changes (wild-type virus)	0 participants	0 participants	1 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) Unable to be genotyped	1 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline; Weeks 337 to 384

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 336 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 384 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 336 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 336 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Outcome measures

Measure	TDF-TDF n=87 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=12 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=50 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC n=10 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) Participants evaluated	1 participants	0 participants	2 participants	2 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	0 participants	0 participants	1 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	0 participants	0 participants	1 participants	1 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) No genotypic changes (wild-type virus)	0 participants	0 participants	0 participants	1 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) Unable to be genotyped	1 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline; Weeks 385 to 432

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 384 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 432 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 384 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 384 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Outcome measures

Measure	TDF-TDF n=49 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=10 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=26 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC n=4 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) Participants evaluated	1 participants	3 participants	0 participants	1 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	0 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	1 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) No genotypic changes (wild-type virus)	0 participants	3 participants	0 participants	1 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) Unable to be genotyped	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline; Weeks 433 to 480

Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 432 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.

Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 480 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 432 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 432 and had HBV DNA ≥ 400 copies/mL at the time of the addition.

Outcome measures

Measure	TDF-TDF n=47 Participants TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV 10 mg n=10 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.	ADV-TDF n=26 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group did not add FTC to their study regimen in the open-label period.	ADV-TDF With Addition of FTC n=3 Participants ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants in this reporting group added FTC (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their study regimen in the open-label period.
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) Participants evaluated	0 participants	3 participants	1 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) Changes at conserved sites in HBV polymerase	0 participants	0 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	0 participants	1 participants	0 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) No genotypic changes (wild-type virus)	0 participants	2 participants	1 participants	0 participants
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) Unable to be genotyped	0 participants	0 participants	0 participants	0 participants

Adverse Events

Double-Blind TDF

Serious events: 15 serious events

Other events: 97 other events

Deaths: 0 deaths

Double-Blind ADV

Serious events: 7 serious events

Other events: 49 other events

Deaths: 0 deaths

Open-Label TDF

Serious events: 41 serious events

Other events: 165 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double-Blind TDF n=176 participants at risk Adverse events this reporting group include those occurring in the TDF-TDF group during the double-blind period only (baseline to Week 48). TDF 300 mg plus placebo to match ADV (double-blind period).	Double-Blind ADV n=90 participants at risk Adverse events this reporting group include those occurring in the ADV-TDF group during the double-blind period only (baseline to Week 48). ADV 10 mg plus placebo to match TDF (double-blind period).	Open-Label TDF n=238 participants at risk Adverse events for this reporting group include those occurring during the open-label TDF 300 mg period (Week 49 up to Week 480), regardless of which group they were randomized to in the double-blind period. TDF 300 mg + ADV placebo or ADV 10 mg + TDF placebo (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Blood and lymphatic system disorders Thrombocytopenia	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Acute myocardial infarction	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Angina pectoris	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Ischaemic cardiomyopathy	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Myocarditis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Congenital, familial and genetic disorders Congenital anomaly in offspring	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Inguinal hernia	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
General disorders Chest pain	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.1% 1/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis chronic	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.1% 1/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Hepatobiliary disorders Hepatitis	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Abscess soft tissue	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Diverticulitis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Epididymitis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Gastroenteritis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Groin abscess	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Hepatitis B	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Orchitis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Respiratory tract infection	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Sepsis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Skin infection	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.1% 1/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Procedural dizziness	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Skull fracture	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Ulna fracture	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Investigations Alanine aminotransferase increased	3.4% 6/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.4% 4/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	2.5% 6/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	1.1% 2/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.1% 1/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.84% 2/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Investigations Blood creatine phosphokinase increased	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Investigations Glucose urine present	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.84% 2/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.1% 1/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Synovial cyst	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer metastatic	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.84% 2/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.84% 2/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tonsillar neoplasm	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Diabetic neuropathy	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Facial spasm	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Seizure	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Transient ischaemic attack	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.84% 2/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Psychiatric disorders Drug dependence	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Renal and urinary disorders Calculus ureteric	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.3% 3/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Renal and urinary disorders Tubulointerstitial nephritis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Reproductive system and breast disorders Ovarian cyst ruptured	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Surgical and medical procedures Abortion induced	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Vascular disorders Thrombosis	0.00% 0/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.00% 0/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.42% 1/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.

Other adverse events

Measure	Double-Blind TDF n=176 participants at risk Adverse events this reporting group include those occurring in the TDF-TDF group during the double-blind period only (baseline to Week 48). TDF 300 mg plus placebo to match ADV (double-blind period).	Double-Blind ADV n=90 participants at risk Adverse events this reporting group include those occurring in the ADV-TDF group during the double-blind period only (baseline to Week 48). ADV 10 mg plus placebo to match TDF (double-blind period).	Open-Label TDF n=238 participants at risk Adverse events for this reporting group include those occurring during the open-label TDF 300 mg period (Week 49 up to Week 480), regardless of which group they were randomized to in the double-blind period. TDF 300 mg + ADV placebo or ADV 10 mg + TDF placebo (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period.
Gastrointestinal disorders Abdominal pain	3.4% 6/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	3.3% 3/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	9.2% 22/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	8.5% 15/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.4% 4/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	10.5% 25/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	6.8% 12/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	3.3% 3/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.0% 12/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Nausea	14.8% 26/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.1% 1/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	3.8% 9/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
General disorders Fatigue	12.5% 22/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	8.9% 8/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	8.4% 20/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
General disorders Influenza like illness	5.1% 9/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	3.3% 3/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.9% 14/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Immune system disorders Seasonal allergy	2.3% 4/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.1% 1/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	7.1% 17/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Bronchitis	1.1% 2/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.4% 4/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.5% 13/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Influenza	4.5% 8/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.6% 5/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	10.5% 25/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Nasopharyngitis	12.5% 22/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	14.4% 13/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	18.1% 43/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	4.0% 7/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	6.7% 6/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	8.8% 21/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Investigations Creatinine renal clearance decreased	0.57% 1/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.1% 1/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.0% 12/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	2.8% 5/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	6.7% 6/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	7.1% 17/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	7.4% 13/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	3.3% 3/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	7.6% 18/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.1% 2/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	3.3% 3/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	6.3% 15/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	4.5% 8/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.6% 5/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.6% 11/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Dizziness	6.8% 12/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	2.2% 2/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.6% 11/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Headache	17.6% 31/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	15.6% 14/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	12.6% 30/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	5.7% 10/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.6% 5/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	12.6% 30/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.5% 8/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.6% 5/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	7.6% 18/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Vascular disorders Hypertension	1.7% 3/176 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.1% 1/90 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	10.1% 24/238 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.

Additional Information

Clinical Trial Disclosures

Gilead Sciences, Inc.

Email: ClinicalTrialDisclosures@gilead.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institution and investigator may publish or present the results of the trial generated there with prior written consent of Gilead; or 2 years after the trial has ended at all institutions. Proposed publications/target venue must go to Gilead 30 days (manuscripts) or 15 days (abstracts/presentations) prior. Any Gilead confidential information in the document(s) must be deleted, or if requested publication delayed for up to 45 days to permit Gilead to obtain intellectual property protection.
• Publication restrictions are in place

Restriction type: OTHER